Ubiquitin

Inhibitors of the ATPase p97/VCP: From basic research to clinical applications

0 | Jan 22 2024

In this review, the focus lies on the development and evolution of various p97 inhibitors, notably ATPase inhibitors like CB-5083 and CB-5339, which have exhibited potent anti-tumor activity across diverse models, offering a promising approach for cancer therapy by targeting protein degradation pathways. [Read the Full Post]

PR-957 retards rheumatoid arthritis progression and inflammation by inhibiting LMP7-mediated CD4+ T cell imbalance

209 | Jan 21 2024

PR-957 demonstrates potential in alleviating rheumatoid arthritis by targeting LMP7-mediated CD4+ T cell imbalances, offering a promising avenue for therapeutic intervention. [Read the Full Post]

Gastrodin overcomes chemoresistance via inhibiting Skp2-mediated glycolysis

235 | Jan 18 2024

The study highlights the potential of targeting the Skp2-Akt axis and utilizing gastrodin, inhibiting HK2-mediated glucose metabolism and promoting apoptosis, as a promising combined therapeutic approach for overcoming cisplatin resistance in oral squamous cell carcinoma (OSCC). [Read the Full Post]

MitoCur-1 induces ferroptosis to reverse vemurafenib resistance in melanoma through inhibition of USP14

117 | Jan 16 2024

The discovery of MitoCur-1's ability to inhibit USP14 and induce ferroptosis presents a promising avenue for reversing vemurafenib resistance in melanoma, potentially transforming treatment outcomes for patients. [Read the Full Post]

Inhibition of USP2 Enhances TRAIL-Mediated Cancer Cell Death through Downregulation of Survivin

110 | Jan 06 2024

The study reveals that targeting Ubiquitin-specific protease 2 (USP2) using the inhibitor ML364 enhances TNF-related apoptosis-inducing ligand (TRAIL)-induced cancer cell death selectively by promoting ubiquitination and degradation of survivin, offering a potential avenue for targeted cancer therapies. [Read the Full Post]

The therapeutic effect of glycyrrhizic acid compound ointment on imiquimod-induced psoriasis-like disease in mice

145 | Jan 04 2024

The compound ointment containing glycyrrhetinic acid and herbal monomers exhibited superior efficacy in ameliorating Imiquimod-induced psoriasis-like symptoms in mice, significantly reducing inflammatory factors and demonstrating a stronger therapeutic effect compared to calcipotriol ointment. [Read the Full Post]

A Degron Blocking Strategy Towards Improved CRL4CRBN Recruiting PROTAC Selectivity

126 | Dec 28 2023

Your work addressing selectivity challenges in PROTAC design by leveraging structural insights and computational modeling offers valuable principles and tools crucial for advancing targeted protein degradation strategies. [Read the Full Post]

Degradation of Cyclin-Dependent Kinase 9/Cyclin T1 by Optimized Microtubule-Associated Protein 1 Light Chain 3 Beta-Recruiting Coumarin Analogs

291 | Dec 24 2023

Researchers systematically optimized coumarin analogs linked with the CDK9 inhibitor SNS-032, potentially enabling simultaneous binding to CDK9 and LC3B, initiating selective autophagic degradation and demonstrating potential for treating diseases associated with intracellular pathogenic proteins. [Read the Full Post]

The Ubiquitin-Proteasome System Facilitates Membrane Fusion and Uncoating during Coronavirus Entry

188 | Dec 19 2023

Inhibiting the ubiquitin-proteasome system (UPS) at the early infection stage severely impairs the infectivity of Infectious Bronchitis Virus (IBV) and Porcine Epidemic Diarrhea Virus (PEDV) by preventing membrane fusion, uncoating, initial translation, and replication events, highlighting the UPS as a potential target for antiviral therapies against coronaviruses. [Read the Full Post]

Therapeutical interference with the epigenetic landscape of germ cell tumors: a comparative drug study and new mechanistical insights

235 | Dec 15 2023

The study identified seven epigenetic inhibitors that efficiently decreased cell viability in cisplatin-resistant Type II germ cell tumors, highlighting their potential as alternative therapeutic options, and provided comprehensive insights into their off-target effects and modes of action. [Read the Full Post]

Unlocking the potential of approved drugs for the allosteric inhibition of tropomyosin-receptor kinase A using molecular docking and molecular dynamics studies

175 | Dec 04 2023

The study identified delanzomib and tibalosin as potential allosteric inhibitors of TrkA through molecular docking and dynamics simulations, offering promising candidates for experimental evaluation in cancer therapy due to their stable interactions and high binding affinities. [Read the Full Post]

Entropy driven cooperativity effect in multi-site drug optimization targeting SARS-CoV-2 papain-like protease

138 | Nov 28 2023

The study investigated the enhanced binding affinity between the papain-like protease (PLpro) of SARS-CoV-2 and the existing drug GRL0617, revealing that optimization of specific regions in the drug led to increased cooperativity by stabilizing key residues and reducing entropic loss, providing valuable insights for drug development strategies targeting PLpro. [Read the Full Post]

Ubiquitin-specific protease 20 in human disease: Emerging role and therapeutic implications

77 | Nov 22 2023

The discovery of USP20's diverse physiological roles, including its involvement in metabolic disorders and neurological diseases, alongside the development of specific inhibitors like GSK2643943A, highlights its potential as a valuable therapeutic target for a wide array of diseases. [Read the Full Post]

Ginkgolic acid inhibits the replication of pseudorabies virus in vitro and in vivo by suppressing the transcription of viral late genes

148 | Nov 22 2023

Ginkgolic acid has been identified as a potent inhibitor of pseudorabies virus (PRV) replication by specifically suppressing the transcription of PRV late genes, offering a promising therapeutic avenue for combating PRV infections in the swine industry. [Read the Full Post]

A Reliable and Effective UPLC-MS/MS Method for the Determination of Oprozomib in Rat Plasma

217 | Nov 10 2023

In this experiment, a sensitive UPLC-MS/MS method was successfully validated for quantifying oprozomib concentrations in rat plasma, demonstrating its suitability for pharmacokinetic studies and potential use in assessing the treatment of haematological malignancies, including relapsed refractory multiple myeloma. [Read the Full Post]

Inhibition of CDC20 potentiates anti-tumor immunity through facilitating GSDME-mediated pyroptosis in prostate cancer

206 | Nov 10 2023

The study reveals that CDC20 negatively regulates pyroptosis by targeting GSDME for ubiquitin-mediated proteolysis in prostate cancer, and its inhibition enhances anti-tumor immunity and synergizes with anti-PD1-based immunotherapy, offering novel therapeutic avenues for this cancer type. [Read the Full Post]

SUMOylation of Rho-associated protein kinase 2 induces goblet cell metaplasia in allergic airways

60 | Nov 07 2023

The study reveals that protein SUMOylation-mediated activation of ROCK2, facilitated by PIAS1 and involving Rho/ROCK signaling, is a key mechanism in the development of goblet cell metaplasia in allergic asthma, suggesting that targeting SUMOylation could be a potential therapeutic intervention for the disease. [Read the Full Post]

Selective USP7 inhibition elicits cancer cell killing through a p53-dependent mechanism

127 | Oct 10 2023

XL177A, a potent and selective USP7 inhibitor, demonstrates p53-dependent growth suppression and TP53 mutational status as a potential biomarker for response, showing promise as a targeted therapeutic agent in cancer, including pediatric cancers such as Ewing sarcoma and malignant rhabdoid tumor. [Read the Full Post]

The role of E3 ubiquitin ligase in multiple myeloma: potential for cereblon E3 ligase modulators in the treatment of relapsed/refractory disease

104 | Sep 13 2023

The emerging field of targeted protein degradation, particularly through the redirection of the ubiquitin-proteasome system, offers promising prospects for novel therapeutic approaches in multiple myeloma and other diseases. [Read the Full Post]

Nedd8-Activating Enzyme Is a Druggable Host Dependency Factor of Human and Mouse Cytomegalovirus

238 | Sep 02 2023

The study suggests that the Nedd8-activating enzyme (NAE), the neddylation process, and cullin RING ubiquitin ligases (CRLs) are potential targets for developing drugs against cytomegalovirus infections. [Read the Full Post]

Protection of Regulatory T Cells from Fragility and Inactivation in the Tumor Microenvironment

238 | Aug 29 2023

Downregulation of the IFNAR1 chain in intratumoral Treg cells, mediated by p38α kinase, protects them from fragility and maintains their immunosuppressive activities, while targeting sumoylation with the inhibitor TAK981 induces Treg fragility and inhibits tumor growth, offering potential therapeutic approaches for enhancing immunotherapies against cancer. [Read the Full Post]

Exposure-Response Analysis to Assess the Concentration-QTc Relationship of Iberdomide

210 | Aug 24 2023

The study suggests that iberdomide, at its maximum plasma concentration, does not have a clinically relevant effect on QT interval prolongation. [Read the Full Post]

A Phase 1, Multicenter, Open-Label Study to Evaluate the Pharmacokinetics of Iberdomide in Subjects with Mild, Moderate, or Severe Hepatic Impairment Compared with Healthy Subjects

220 | Aug 24 2023

The phase 1 study demonstrated that hepatic impairment had no clinically significant impact on the pharmacokinetics of iberdomide, supporting the conclusion that no dose adjustment is necessary for patients with hepatic impairment. [Read the Full Post]

Effects of arsenic on the topology and solubility of promyelocytic leukemia (PML)-nuclear bodies

120 | Aug 21 2023

Trivalent arsenic (As3+) induces a solubility shift in PML, leading to rapid SUMOylation and late agglomeration of PML nuclear bodies (PML-NBs), which has implications for the regulation of intranuclear dynamics in the context of acute promyelocytic leukemia (APL). [Read the Full Post]

VH298-loaded extracellular vesicles released from gelatin methacryloyl hydrogel facilitate diabetic wound healing by HIF-1α-mediated enhancement of angiogenesis

299 | Aug 03 2023

This study demonstrates the potential of VH298-loaded extracellular vesicles (EVs) and GelMA hydrogel as a promising therapeutic strategy for diabetic wound treatment, promoting angiogenesis and enhancing wound healing. [Read the Full Post]

UBA1 inhibition contributes radiosensitization of glioblastoma cells via blocking DNA damage repair

276 | Jul 29 2023

The study demonstrated that the UBA1 inhibitor TAK-243, in combination with ionizing radiation, effectively inhibited GBM cell proliferation, impaired DNA double-strand break repair, and increased apoptosis, providing a potential therapeutic approach to enhance the radiation sensitivity of GBM. [Read the Full Post]

Proteasomal pathway inhibition as a potential therapy for NF2-associated meningioma and schwannoma

223 | Jul 29 2023

This study highlights the potential of proteasome pathway inhibitors, specifically ixazomib and TAK-243, as novel and promising therapies for NF2-associated tumors, demonstrating efficacy in preclinical models and laying the groundwork for future clinical investigations. [Read the Full Post]

pH-sensitive smart indicators based on cellulose and different natural pigments for tracing kimchi ripening stages

615 | Jul 27 2023

The study found that cellulose-based pH-sensitive indicators loaded with natural pigments showed more pronounced color changes in response to lactic acid and pH variations, with alkalized indicators being particularly effective for monitoring the fermentation process of acidic foods such as kimchi. [Read the Full Post]

Inhibitors of the ATPase p97/VCP: From basic research to clinical applications

296 | Jul 17 2023

The development of p97 inhibitors as UPS-targeting cancer therapies represents a promising approach for addressing protein homeostasis deficiencies underlying various cancers and neurodegenerative diseases. [Read the Full Post]

Combined inhibition of XIAP and autophagy induces apoptosis and differentiation in acute myeloid leukaemia

197 | Jul 03 2023

In acute myeloid leukemia (AML), the inhibition of X-linked inhibitor of apoptosis (XIAP) induces autophagy, apoptosis, and differentiation, and combining XIAP inhibition with autophagy inhibition shows promise as a therapeutic strategy for AML. [Read the Full Post]

USP1 promotes the aerobic glycolysis and progression of T-cell acute lymphoblastic leukemia via PLK1/LDHA axis

86 | Jun 13 2023

The study demonstrated that the upregulation of deubiquitinase USP1 in pediatric T-ALL correlated with poor prognosis, and its inhibition attenuated glycolytic metabolism and cellular proliferation, suggesting USP1 as a promising therapeutic target. [Read the Full Post]

Targeting mitochondrial energetics reverses panobinostat- and marizomib-induced resistance in pediatric and adult high-grade gliomas

124 | Jun 12 2023

This study investigates the molecular mechanisms and vulnerabilities associated with acquired resistance to the combination therapy of panobinostat and marizomib in high-grade gliomas, highlighting the importance of targeting glycolysis and mitochondrial function to overcome resistance. [Read the Full Post]

Proteasome inhibitors in medullary thyroid carcinoma: time to restart with clinical trials?

146 | Jun 11 2023

This review summarizes the available in vitro and in vivo data on the role of proteasome inhibitors (PrIn) in medullary thyroid cancer (MTC) and highlights the need for further clinical trials to explore their potential as a treatment option for MTC patients. [Read the Full Post]

Targeting endoplasmic reticulum associated degradation pathway combined with radiotherapy enhances the immunogenicity of esophageal cancer cells

62 | Jun 01 2023

The study found that inhibiting ERAD pathways combined with moderate dose radiation therapy can enhance the immunogenicity of esophageal cancer cells, leading to an improved antitumor immune response and favorable clinical outcomes. [Read the Full Post]

Administration of USP7 inhibitor P22077 inhibited cardiac hypertrophy and remodeling in Ang II-induced hypertensive mice

64 | May 24 2023

USP7 may be a new therapeutic target for hypertrophic remodeling and heart failure due to its involvement in multiple signaling pathways that contribute to cardiac hypertrophy and remodeling. [Read the Full Post]

Patients with infective endocarditis undergoing cardiac surgery have distinct ROTEM profiles and more bleeding complications compared to patients without infective endocarditis

276 | May 24 2023

This exploratory investigation found significantly altered coagulation profiles in patients with infective endocarditis, with concomitant hyper- and hypocoagulability, leading to increased bleeding complications and transfusion requirements, and suggests the need for adjustments to existing coagulation management algorithms in these high-risk patients. [Read the Full Post]

Inhibitors of the Ubiquitin-Mediated Signaling Pathway Exhibit Broad-Spectrum Antiviral Activities against New World Alphaviruses

91 | May 24 2023

The study investigated the use of small molecule inhibitors that interfere with UPS-associated signaling pathways as potential therapeutic candidates for treating mosquito-transmitted alphaviruses such as VEEV and EEEV, and found that three of them exhibited broad-spectrum antiviral activity against both viruses. [Read the Full Post]

Ubiquitin-Specific Proteases as Potential Therapeutic Targets in Bladder Cancer-In Vitro Evaluation of Degrasyn and PR-619 Activity Using Human and Canine Models

172 | May 23 2023

The study found that Degrasyn showed greater anti-cancer activity against bladder cancer cell lines compared to the non-selective DUB inhibitor PR-619, inducing caspase-dependent apoptosis and triggering DNA damage. [Read the Full Post]

An unconventional SNARE complex mediates exocytosis at the plasma membrane and vesicular fusion at the apical annuli in Toxoplasma gondii

109 | Apr 20 2023

An unconventional SNARE complex comprising TgStx1, TgStx20, and TgStx21 mediates vesicular fusion at the plasma membrane in T. gondii, indicating a unique mechanism for exocytosis in this organism. [Read the Full Post]

Regulation of programmed death ligand 1 expression by interferon-γ and tumour necrosis factor-α in canine tumour cell lines

184 | Apr 12 2023

The study demonstrates that upregulation of PD-L1 expression in canine tumours is regulated by the JAK-STAT and NF-κB signaling pathways upon stimulation with IFN-γ and TNF-α, respectively. [Read the Full Post]

The cytotoxic activity of carfilzomib together with nelfinavir is superior to the bortezomib/nelfinavir combination in non-small cell lung carcinoma

258 | Apr 09 2023

Combining carfilzomib with nelfinavir shows superior efficacy in inducing proteotoxicity and endoplasmic reticulum stress in non-small-cell-lung carcinoma (NSCLC) compared to the combination of bortezomib and nelfinavir, and may represent a future treatment option for NSCLC. [Read the Full Post]

Lipopolysaccharide sensitizes the therapeutic response of breast cancer to IAP antagonist

186 | Apr 03 2023

The study shows that LPS enhances the therapeutic response of IAP antagonists in treating triple-negative and ER+ breast cancer by inducing rapid apoptosis of cancer cells through TLR4- and MyD88-mediated production of TNFα, and suggests that antibiotics that can reduce microbiota-derived LPS should not be used together with an IAP antagonist for cancer therapy. [Read the Full Post]

Age-related cataract: GSTP1 ubiquitination and degradation by Parkin inhibits its anti-apoptosis in lens epithelial cells

196 | Mar 26 2023

This study demonstrates that oxidative stress-induced apoptosis of lens epithelial cells in age-related cataract is regulated by E3 ligase Parkin-mediated degradation of GSTP1, providing potential targets for ARC therapy. [Read the Full Post]

WP1130 relieves septic shock in mice by inhibiting NLRP3 inflammasome activation

246 | Mar 20 2023

WP1130 specifically inhibits NLRP3 inflammasome activation and alleviates septic shock in mice. [Read the Full Post]

USP9x promotes CD8 + T-cell dysfunction in association with autophagy inhibition in septic liver injury

254 | Mar 20 2023

This study suggests that USP9x inhibition could be a potential therapeutic target for septic liver injury by promoting CD8+ T-cell function via autophagy regulation. [Read the Full Post]

Molecular Cardiotoxic Effects of Proteasome Inhibitors Carfilzomib and Ixazomib and Their Combination with Dexamethasone Involve Mitochondrial Dysregulation

295 | Mar 16 2023

The study suggests that proteasome inhibitors may cause cardiotoxicity through stress response and mitochondrial dysfunction, which highlights the need for further studies to develop strategies to minimize their side effects. [Read the Full Post]

Clinical efficacy of retreatment of daratumumab-based therapy (D2) in daratumumab-refractory multiple myeloma

184 | Feb 26 2023

In a study of 43 patients with daratumumab-refractory multiple myeloma, a combination of daratumumab-based retreatment with different classes of anti-myeloma drugs showed a 49% response rate, with a median progression-free survival of 7.97 months and a median overall survival of 32.6 months. [Read the Full Post]

Change in Cutibacterium acnes phylotype abundance and improvement of clinical parameters using a new dermocosmetic product containing Myrtus communis and Celastrol enriched plant cell culture extracts in patients with acne vulgaris

338 | Feb 15 2023

The new dermocosmetic product containing Myrtus communis and Celastrol-enriched plant cell culture extracts improved acne severity by decreasing pro-pathogen phylotype IC and increasing non-pathogen phylotype IB of Cutibacterium acnes and decreasing acne lesion count and improving the Global Evaluation Acne score. [Read the Full Post]

Celastrol suppresses colorectal cancer via covalent targeting peroxiredoxin 1

201 | Feb 14 2023

A text-mining-based web-server tool was used to identify peroxiredoxin 1 (PRDX1) as the ROS-manipulating target of Celastrol, a natural product isolated from the plant Thunder God Vine, and the anti-tumor efficacy of Celastrol was reduced in colorectal cancer cells by inhibiting PRDX1, and a new derivative compound 19-048 with improved potency against PRDX1 was synthesized. [Read the Full Post]

Optimizing the value of lenalidomide maintenance by genetic profiling - an analysis of 556 Myeloma XI trial patients

301 | Dec 30 2022

Aikaterini Panopoulou et al. found that extended genetic profiling identified patients deriving exceptional benefit from Len maintenance. [Read the Full Post]

Desensitization Protocol to Lenalidomide: An Effective and Safe Treatment Modality for Delayed Hypersensitivity-induced Rash in Patients with Multiple Myeloma

408 | Dec 29 2022

Oded Shamriz et al. thought that desensitization to lenalidomide was safe and effective. [Read the Full Post]

Upfront autologous haematopoietic stem-cell transplantation versus carfilzomib-cyclophosphamide-dexamethasone consolidation with carfilzomib maintenance in patients with newly diagnosed multiple myeloma in England and Wales (CARDAMON): a randomised, phase 2, non-inferiority trial

439 | Dec 23 2022

Kwee Yong et al. thought that KCd did not meet the criteria for non-inferiority compared with autologous HSCT, but the marginal difference in progression-free survival suggested that further studies were warranted to explore deferred autologous HSCT in some subgroups. [Read the Full Post]

Epoxomicin, a Selective Proteasome Inhibitor, Activates AIM2 Inflammasome in Human Retinal Pigment Epithelium Cells

131 | Dec 07 2022

Iswariyaraja Sridevi Gurubaran et al. thought that a selective proteasome inhibitor was a potent inflammasome activator in human RPE cells. [Read the Full Post]

Prolonged activation of NMDA receptors induces dedifferentiation of islet β cells in mice

136 | Dec 07 2022

Xiaoting Huang et al. found that prolonged activation of NMDA receptors induced islet β-cell dedifferentiation via regulating the NF-κB pathway. [Read the Full Post]

Targeting the USP7/RRM2 axis drives senescence and sensitizes melanoma cells to HDAC/LSD1 inhibitors

87 | Nov 25 2022

Letizia Granieri et al. thought that RRM2 was a USP7 target and was regulated by USP7 during S phase of the cell cycle. [Read the Full Post]

The multifaceted roles of USP7: new therapeutic opportunities

121 | Nov 25 2022

Benjamin Nicholson et al. thought that USP7 inhibitors held promise as a new strategy for the treatment of disease. [Read the Full Post]

Early growth response-1 is a new substrate of the GSK3β-FBXW7 axis

115 | Oct 17 2022

Lu Yin et al. found that EGR1 was a new substrate of the GSK3β-FBXW7 axis, and the FBXW7-EGR1 axis coordinately regulated growth of cancer cells. [Read the Full Post]

The CRTC-CREB axis functions as a transcriptional sensor to protect against proteotoxic stress in Drosophila

129 | Oct 02 2022

Youjie Yin et al. identified CRTC/CREB downstream ROS/JNK signaling as a conserved sensor to tackle oxidative and proteotoxic stresses. [Read the Full Post]

Phase 1 study to evaluate the effects of rifampin on pharmacokinetics of pevonedistat, a NEDD8-activating enzyme inhibitor in patients with advanced solid tumors

108 | Aug 17 2022

Xiaofei Zhou et al, supported the recommendation that no pevonedistat dose adjustment was needed for patients receiving concomitant CYP3A inducers. [Read the Full Post]

Murine Double Minute 2 Antagonist Nutlin-3 Enhanced Chemosensitivity in Esophageal Squamous Cell Carcinoma

177 | Jul 31 2022

Ken Ito et al. found that the combination of nutlin-3 with chemotherapeutic agents might become a novel therapeutic strategy in esophageal cancer over-expressing MDM2. [Read the Full Post]

Carfilzomib plus dexamethasone in patients with relapsed and refractory multiple myeloma: a retro-prospective observational study

259 | Jul 04 2022

Maria Livia Del Giudice et al. thought that Kd56 was an effective and well tolerated regimen in highly pretreated and elderly patients with a good safety profile. [Read the Full Post]

Construction and evaluation of detachable bone-targeting MOF carriers for the delivery of proteasome inhibitors

476 | Jun 17 2022

Hongbing Yang et al. provided a potential cascade targeting strategy for improving the delivery effects of bone targeted nanoparticles for the delivery of proteasome inhibitors. [Read the Full Post]

Rutaecarpine Attenuates Oxidative Stress-Induced Traumatic Brain Injury and Reduces Secondary Injury via the PGK1/KEAP1/NRF2 Signaling Pathway

245 | May 24 2022

Min Xu et al. showed that rutaecarpine might be a promising therapeutic agent for the treatment of TBI-related neuro-oxidative damage. [Read the Full Post]

[Ocular toxicity of targeted therapies with MEK inhibitors and BRAF inhibitors in the treatment of metastatic cutaneous melanoma]

416 | May 06 2022

E Fauviaux et al. found that a multidisciplinary approach including ophthalmologists, dermatologists and oncologists was essential in order to adapt treatment in the advent of the ocular complications. [Read the Full Post]

SLFN11 biomarker status predicts response to lurbinectedin as a single agent and in combination with ATR inhibition in small cell lung cancer

652 | Apr 27 2022

Kiran Kundu et al. provided a rationale for lurbinectedin in combination with ATR inhibitors to overcome resistance in SCLC with low SLFN11 expression. [Read the Full Post]

GRP78 blockade overcomes intrinsic resistance to UBA1 inhibitor TAK-243 in glioblastoma

370 | Apr 10 2022

Xu Zhang et al. provided a new strategy for improving the sensitivity of GBM to TAK-243 treatment and experimental basis for further clinical trials to evaluate this combination therapy. [Read the Full Post]

Neddylation is essential for β-catenin degradation in Wnt signaling pathway

489 | Apr 10 2022

Bojun Wang et al. highlighted the importance of reassessing previously identified ubiquitylation substrates. [Read the Full Post]

The p97 Inhibitor UPCDC-30245 Blocks Endo-Lysosomal Degradation

304 | Mar 13 2022

Feng Wang et al. found UPCDC-30245 exhibited antiviral effects against coronavirus by blocking viral entry. [Read the Full Post]

RSL3 Drives Ferroptosis through NF- κ B Pathway Activation and GPX4 Depletion in Glioblastoma

390 | Jan 14 2022

Shengbiao Li et al. found that the NF-κB pathway played a novel role in RSL3-induced ferroptosis in glioblastoma cells. [Read the Full Post]

Protein Kinase A (PRKA) Activity Is Regulated by the Proteasome at the Onset of Human Sperm Capacitation

385 | Jan 13 2022

Héctor Zapata-Carmona et al. suggested that PRKAR1 was the target of PRKA regulation by the proteasome. [Read the Full Post]

USP7 inhibition induces apoptosis in glioblastoma by enhancing ubiquitination of ARF4

215 | Jan 02 2022

Tingzheng Pan et al. thought that P5091 as a novel specific inhibitor of USP7 might be an effective approach for the treatment of GBM. [Read the Full Post]

Blocking neddylation elicits antiviral effect against hepatitis B virus replication

223 | Nov 23 2021

Karima Abounouh et al. provided new tools interfering with HBV persistence as well as novel therapeutic strategies against chronic hepatitis B. [Read the Full Post]

Selective Targeting of Cancerous Mitochondria and Suppression of Tumor Growth Using Redox-Active Treatment Adjuvant

567 | Nov 11 2021

Rumiana Bakalova et al. thought that M/A-mediated anticancer effects were triggered by redox cycling of both substances, specifically within dysfunctional mitochondria. [Read the Full Post]

Pevonedistat attenuates cisplatin-induced nephrotoxicity in mice by downregulating the release of inflammatory mediators

331 | Sep 22 2021

Yousra M El-Far et al. found that pevonedistat alleviated CIS-induced nephrotoxicity that might be attributed to suppression of the inflammation induced in renal tissue. [Read the Full Post]

The balance between p53 isoforms modulates the efficiency of HIV-1 infection in macrophages

542 | Sep 06 2021

Yann Breton et al. demonstrated the involvement of p53 isoforms, which regulated p53 activity and defined the cellular environment influencing viral replication. [Read the Full Post]

Sinus rhythm heart rate increase after atrial fibrillation ablation is associated with lower risk of arrhythmia recurrence

1034 | Aug 11 2021

Ammar M Killu et al. showed that relative changes in HR post AF ablation correlates with AF recurrence. [Read the Full Post]

Outcome of COVID-19 infection in 50 multiple myeloma patients treated with novel drugs: single-center experience

1440 | Jul 27 2021

Marta Krejci et al. found that the course of COVID-19 disease in MM pts was mostly moderate or serious with 56% of hospitalizations and 18% of deaths. [Read the Full Post]

Differential Expression of Inflammasome-Related Genes in Induced Pluripotent Stem-Cell-Derived Retinal Pigment Epithelial Cells with or without History of Age-Related Macular Degeneration

674 | Jul 05 2021

Maria Hytti et al. suggested that cellular clearance mechanisms might already be dysfunctional, and the inflammasome activated, in cells with a disease origin. [Read the Full Post]

Real-world-evidence-for-carfilzomib-dosing-intensity-on-overall-survival-and-treatment-progression-in-multiple-myeloma-patients

832 | Jun 13 2021

Noopur Raje found that patient outcomes could be improved if eligible MM patients are treated with the optimized [Read the Full Post]

Phase 1 study of the ATR inhibitor berzosertib (formerly M6620, VX-970) combined with gemcitabine ± cisplatin in patients with advanced solid tumours

1118 | Jun 02 2021

Mark R Middleton et al. found that Berzosertib + gemcitabine was well tolerated in patients with advanced solid tumours and showed preliminary efficacy signs. [Read the Full Post]

Direct Conjugation of NEDD8 to the N-Terminus of a Model Protein Can Induce Degradation

657 | May 03 2021

Kartikeya Vijayasimha et al. suggested that under certain conditions, such as the model system described here, the covalent linkage of NEDD8 to a protein substrate might result in the target proteins degradation. [Read the Full Post]

SLFN11 inactivation induces proteotoxic stress and sensitizes cancer cells to ubiquitin activating enzyme inhibitor TAK-243

643 | May 01 2021

Yasuhisa Murai et al. found that findings uncover a previously unknown function of SLFN11 as a regulator of protein quality control and attenuator of ER stress and UPR. Moreover, they suggest the potential value of TAK-243 in SLFN11-deficient tumors. [Read the Full Post]

Comprehensive analysis of ubiquitin-specific protease 1 reveals its importance in hepatocellular carcinoma

349 | Mar 28 2021

Yalei Zhao et al. found that USP1 was a promising target for HCC treatment with good prognostic value. [Read the Full Post]

A covalent p97/VCP ATPase inhibitor can overcome resistance to CB-5083 and NMS-873 in colorectal cancer cells

521 | Mar 26 2021

Gang Zhang et al. identified and characterized PPA as a selective covalent p97 inhibitor, which would allow future exploration to improve the potency of p97 inhibitors with different mechanisms of action. [Read the Full Post]

Valve endothelial-interstitial interactions drive emergent complex calcific lesion formation in vitro

626 | Jan 24 2021

Terence W Gee et al. established that VEC actively induced VIC pathological remodeling and calcification via EndMT and paracrine signaling. [Read the Full Post]

Hypoxic modulation of fetal vascular MLCK abundance, localization, and function

614 | Jan 23 2021

Dane W Sorensen et al. found that changes in MLCK distribution are a significant component of fetal vascular responses to hypoxia. [Read the Full Post]

Expression of ubiquitin-specific protease 7 in lung tissue of preterm rats after hyperoxia exposure

327 | Jan 11 2021

Xiao-Yue Huang et al. thought that USP7 specific inhibitor P5091 might accelerate the degradation of β-catenin by enhancing its ubiquitination, reduce lung epithelial-mesenchymal transition, and thus exert a certain protective effect against hyperoxic lung injury. [Read the Full Post]

Neddylation inhibitor MLN4924 has anti-HBV activity via modulating the ERK-HNF1α-C/EBPα-HNF4α axis

503 | Dec 05 2020

Mingjie Xie et al. revealed that neddylation inhibitor MLN4924 had impressive anti-HBV activity by inhibiting HBV replication, thus providing sound rationale for future MLN4924 clinical trial as a novel anti-HBV therapy. [Read the Full Post]

Preclinical evaluation of antitumor activity of the proteasome inhibitor MLN2238 (ixazomib) in hepatocellular carcinoma cells

0 | Nov 20 2020

Giuseppa Augello et al. thought that association of A1210477 and MLN2238 determined synergistic antitumor effects in HCC cells. [Read the Full Post]

Pevonedistat (MLN4924): mechanism of cell death induction and therapeutic potential in colorectal cancer

511 | Sep 15 2020

Jennifer Ferris et al. suggested that this second-generation proteostasis-disrupting agent might have its most widespread activity in CRC, in combination with irinotecan-containing treatment regimens. [Read the Full Post]

Resurrecting a p53 peptide activator - An enabling nanoengineering strategy for peptide therapeutics

649 | Aug 20 2020

Wangxiao He et al. proposed that this clinically viable drug delivery strategy could be applied not only to peptide activators of p53 for cancer therapy, but also to peptide therapeutics in general aimed at targeting intracellular protein-protein interactions for disease intervention. [Read the Full Post]

Proteasome Inhibitor PS-341 Effectively Blocks Infection by the Severe Fever with Thrombocytopenia Syndrome Virus

1172 | Aug 07 2020

Sihua Liu et al. indicated that targeting of cellular interferon pathways and apoptosis during acute infection might serve as the bases of future therapeutics for the treatment of SFTSV infections. [Read the Full Post]

Phase 1 trial of carfilzomib (PR-171) in combination with vorinostat (SAHA) in patients with relapsed or refractory B-cell lymphomas

946 | Jul 16 2020

Beata Holkova et al. showed a decrease in NF-κB activation and an increase in Bim levels in some patients, but these changes did not correlate with clinical response. [Read the Full Post]

Sequential Bortezomib and Temozolomide Treatment Promotes Immunological Responses in Glioblastoma Patients With Positive Clinical Outcomes: A Phase 1B Study

1166 | Jun 25 2020

Mohummad A Rahman et al. found that Sequential BTZ + TMZ treatment was safe and promotes Th1-driven immunological responsed in selected patients with improved clinical outcomes (Clinicaltrial.gov (NCT03643549)). [Read the Full Post]

Targeting the Ubiquitin-Proteasome Pathway to Overcome Anti-Cancer Drug Resistance

659 | Jun 20 2020

Silpa Narayanan et al. discussed various PIs and their underlying mechanisms in surmounting anti-tumor drug resistance when used in combination with conventional chemotherapeutic agents. [Read the Full Post]

MG-132 Attenuates Cardiac Deterioration of Viral Myocarditis via AMPK Pathway

534 | May 28 2020

Xin-Min Zhang et al. found that MG-132 modulated apoptosis and inflammation, improved hemodynamics, and inhibited the structural remodeling of ventricles in a myocarditis mouse model via regulation of the AMPK signal pathway. [Read the Full Post]

Preclinical evaluation of antitumor activity of the proteasome inhibitor MLN2238 (ixazomib) in hepatocellular carcinoma cells

841 | Mar 26 2020

Augello G et al. indicated their results offer hope for a new therapeutic opportunity in the treatment of HCC patients. [Read the Full Post]

Blocking PD1/PDL1 Interactions Together With MLN4924 Therapy Is a Potential Strategy for Glioma Treatment

431 | Feb 26 2020

Natalia Filippova et al. concluded that i) PDL1 up-regulation in gliomas and the glioma microenvironment is an important chemotherapeutic target; ii) MLN4924 therapy, combined with a blockage of the PD1/PDL1 pathway, should be considered as a potential strategy for glioma treatment. [Read the Full Post]

Renal medullary carcinomas depend upon SMARCB1 loss and are sensitive to proteasome inhibition

528 | Feb 14 2020

Hong AL et al. identified a synthetic lethal relationship between SMARCB1-deficient cancers and reliance on the UPS which provides the foundation for a mechanism-informed clinical trial with proteasome inhibitors. [Read the Full Post]

Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001

597 | Jan 28 2020

Shaw AT et al. showed the clinically meaningful benefit and safety of crizotinib in this molecular subgroup. [Read the Full Post]

Daratumumab prevents programmed death ligand-1 expression on antigen-presenting cells in de novo multiple myeloma

512 | Jan 28 2020

Stocker N et al. suggested new mechanisms of action of Dara through depletion of pDC and prevention of PD-L1 upregulation expression on APC. Our finding provides new evidences for development of therapeutic strategies targeting both CD38 and PD-L1/PD-1 pathway in patients with MM. [Read the Full Post]

Diacylglycerol kinase δ destabilizes serotonin transporter protein through the ubiquitin-proteasome system

644 | Jan 04 2020

Lu Q et al. provide novel insights into serotonergic system regulation and the pathophysiology/therapeutics of serotonin-/SERT-related diseases such as obsessive-compulsive disorder, depression, autism and schizophrenia. [Read the Full Post]

Pevonedistat (MLN4924), a First-in-Class NEDD8-activating enzyme inhibitor, in patients with acute myeloid leukaemia and myelodysplastic syndromes: a phase 1 study

0 | Dec 28 2019

Swords RT et al. indicated that administration of the first-in-class agent, pevonedistat, was feasible in patients with MDS and AML and modest clinical activity was observed. [Read the Full Post]

Nutlin-3 enhances the bortezomib sensitivity of p53-defective cancer cells by inducing paraptosis

803 | Nov 01 2019

Lee DM et al. suggested that bortezomib/nutlin-3 perturbs proteostasis, triggering ER/mitochondria stress and irrecoverable impairments in their structure and function, ultimately leading to paraptotic cell death. [Read the Full Post]

Phase 1 trial of carfilzomib (PR-171) in combination with vorinostat (SAHA) in patients with relapsed or refractory B-cell lymphomas

664 | Sep 25 2019

Holkova B et al. showed a decrease in NF-κB activation and an increase in Bim levels in some patients, but these changes did not correlate with clinical response. [Read the Full Post]

Proteasome inhibitor PS-341 limits macrophage necroptosis by promoting cIAPs-mediated inhibition of RIP1 and RIP3 activation

579 | Aug 25 2019

Zhang Y et al. identified a new role of PS-341 in the cell death of BMDMs and provided a novel insight into the atherosclerotic inflammation caused by proteasome-mediated macrophage necroptosis. [Read the Full Post]

Phenotypic Drug Screening for Dysferlinopathy Using Patient-Derived Induced Pluripotent Stem Cells

686 | Jul 24 2019

Kokubu Y et al. suggested that increasing the amount of misfolded dysferlin using small molecules could represent an effective future clinical treatment for dysferlinopathy. Stem Cells Translational Medicine2019. [Read the Full Post]

Pevonedistat (MLN4924), a First-in-Class NEDD8-activating enzyme inhibitor, in patients with acute myeloid leukaemia and myelodysplastic syndromes: a phase 1 study

678 | Jul 08 2019

Swords RT et al. indicated that administration of the first-in-class agent, pevonedistat, was feasible in patients with MDS and AML and modest clinical activity was observed. [Read the Full Post]

Molecular detection of Hsp90 inhibitor suppressing PCV2 replication in host cells

718 | May 13 2019

Liu J et al. highlighted the importance of cellular proteins during PCV2 infection and the possibility of targeting cellular chaperones for developing new anti-rotaviral strategies. [Read the Full Post]

Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma

869 | Mar 17 2019

Moreau P et al. showed the addition of ixazomib to a regimen of lenalidomide and dexamethasone was associated with significantly longer progression-free survival; the additional toxic effects with this all-oral regimen were limited. (Funded by Millennium Pharmaceuticals; TOURMALINE-MM1 ClinicalTrials.gov number, NCT01564537.). [Read the Full Post]

MLN2238 synergizes BH3 mimetic ABT-263 in castration-resistant prostate cancer cells by induction of NOXA

866 | Mar 17 2019

Wei X et al. indicated that NOXA knockdown by short hairpin RNA significantly attenuated the cytotoxicity of ABT-263 and MLN2238 co-administration. In conclusion, MLN2238 and ABT-263 synergistically triggered apoptosis in CRPC cells by upregulating NOXA and activating Bax, indicating a promising therapeutic strategy for the treatment of CRPC. [Read the Full Post]

Nutlin-3, A p53-Mdm2 Antagonist for Nasopharyngeal Carcinoma Treatment

948 | Feb 05 2019

Yee-Lin V et al. Nutlin-3, a small molecule inhibitor that specifically targets p53-Mdm2 interaction offers new therapeutic opportunities by enhancing cancer cell growth arrest and apoptosis through the restoration of the p53-mediated tumor suppression pathway while producing minimal cytotoxicity and side effects. [Read the Full Post]

Methods for 20S Immunoproteasome and 20S Constitutive Proteasome Determination Based on SPRI Biosensors

837 | Dec 06 2018

Anna S et al. indicated 20Si and 20Sc were determined in blood plasma samples from healthy donors and patients with acute leukemia. In the case of these patients 20Si was the major component, and its level was more than one order of magnitude higher than in the healthy donors. [Read the Full Post]

Inhibitors of ubiquitin E3 ligase as potential new antimalarial drug leads

966 | Dec 04 2018

Jain J et al. provided better understanding regarding the importance of E3 ligase functions in the malaria parasite as a potential new antimalarial drug target and a new class of antimalarial drug leads. [Read the Full Post]

Structure-based virtual screening and optimization of modulators targeting Hsp90-Cdc37 interaction

930 | Dec 02 2018

Wang L et al. suggested that compound 10 exhibits moderate inhibitory effect on Hsp90-Cdc37 and could be regard as a first evidence of a non-natural compound targeting Hsp90-Cdc37 PPI. [Read the Full Post]

Loss of XIAP facilitates switch to TNFα-induced necroptosis in mouse neutrophils

2169 | Oct 28 2018

Wicki S et al. may implicated an important role of neutrophils in the development of hyperinflammation and disease progression of patients diagnosed with X-linked lymphoproliferative syndrome type 2, which are deficient in XIAP. [Read the Full Post]

Identification of mTOR as a primary resistance factor of the IAP antagonist AT406 in hepatocellular carcinoma cells

0 | Oct 24 2018

Zhen MC et al. concluded that mTOR could be a key resistance factor of AT406 in HCC cells. [Read the Full Post]

Inhibiting PLK1 induces autophagy of acute myeloid leukemia cells via mammalian target of rapamycin pathway dephosphorylation

0 | Sep 03 2018

Tao YF et al. may provided new insights into the molecular mechanism of PLK1 in regulating autophagy. [Read the Full Post]

Identifying Regulatory Posttranslational Modifications of PD-L1: A Focus on Monoubiquitinaton

717 | Aug 04 2018

Horita H et al. highlights the significance of identifying novel PTMs for PD-L1 and reveals potentially critical regulatory mechanisms that may be valuable therapeutic targets. In a broader context, this report validates an approach whereby one can gain insight into novel mechanisms of action by a simple and unbiased analysis of a PTM profile of potentially any endogenous protein of interest. [Read the Full Post]

Ubiquitin-specific protease 14 regulates cell proliferation and apoptosis in oral squamous cell carcinoma

781 | Jul 06 2018

Chen X et al. found that ubiquitin-specific protease 14 could be a potential therapeutic target for oral squamous cell carcinoma patients. [Read the Full Post]

Inhibition of deubiquitinases primes glioblastoma cells to apoptosis in vitro and in vivo

2008 | Jun 18 2018

Karpel-Massler G et al. suggested that targeting deubiquitinases for glioma therapy is feasible and effective. [Read the Full Post]

The Deubiquitinase USP9X Maintains DNA Replication Fork Stability and DNA Damage Checkpoint Responses by Regulating CLASPIN during S-Phase

2339 | Jun 18 2018

McGarry E et al. revealed a novel role for USP9X in the maintenance of genomic stability during DNA replication and provide potential mechanistic insights into its tumor suppressor role in certain malignancies. [Read the Full Post]

Activation of Chymotrypsin-Like Activity of the Proteasome during Ischemia Induces Myocardial Dysfunction and Death

1441 | Jun 12 2018

Sanchez G et al. suggested that selective inhibition of chymotrypsin-like activity of the proteasome during ischemia preserves key proteins for cardiomyocyte function and exerts a positive impact on cardiac performance after reperfusion. [Read the Full Post]

A novel hypoxia-selective epigenetic agent RRx-001 triggers apoptosis and overcomes drug resistance in multiple myeloma cells

1012 | Jun 03 2018

Das DS et al. provided the rationale for translation of RRx-001, either alone or in combination, to clinical evaluation in MM. [Read the Full Post]

USP7 inhibitor P5091 inhibits Wnt signaling and colorectal tumor growth

949 | Jun 03 2018

An T et al. indicated that USP7 could be a potential drug target and its inhibitor P5091 deserves further development as anticancer agent for Wnt hyper-activated CRC therapy. [Read the Full Post]

Investigating proteasome inhibitors as potential adjunct therapies for experimental cerebral malaria

1160 | May 11 2018

Howland SW et al. reported here that bortezomib, which has been associated with neurological adverse events, accelerated death in ECM-infected mice. [Read the Full Post]

p53-related protein kinase confers poor prognosis and represents a novel therapeutic target in multiple myeloma

1371 | Apr 23 2018

Hideshima T et al. demonstrated that either genetic or pharmacological inhibition of TP53RK triggers MM cell apoptosis via both p53-Myc axis-dependent and axis-independent pathways, validating TP53RK as a novel therapeutic target in patients with poor-prognosis MM. [Read the Full Post]

Diabetes mellitus stimulates pancreatic cancer growth and epithelial-mesenchymal transition-mediated metastasis via a p38 MAPK pathway

0 | Apr 23 2018

Wang L et al. revealed that p38 MAPK inhibitors may provide a novel intervention strategy for diabetic pancreatic cancer treatment. [Read the Full Post]

COPS5 amplification and overexpression confers tamoxifen-resistance in ERα-positive breast cancer by degradation of NCoR

2001 | Apr 14 2018

Lu R et al. demonstrated that genetic inhibition of the isopeptidase activity of COPS5 is sufficient to re-sensitize the resistant breast cancer cells to tamoxifen-treatment, offering a potential therapeutic approach for endocrine-resistant breast cancer patients. [Read the Full Post]

X66, a novel N-terminal heat shock protein 90 inhibitor, exerts antitumor effects without induction of heat shock response.

1190 | Mar 16 2018

Zhao Z et al. found that the HSP90 inhibitory action and the potent antitumor activity, with the anti-HSR action, promise X66 a novel HSP90-targeted agent, which merits further research and development. [Read the Full Post]

Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15

0 | Feb 23 2018

Han T et al. proposed that DCAF15 expression may be a useful biomarker to guide clinical trials of this class of drugs, which we refer to as SPLAMs [Read the Full Post]

Leucovorin Enhances the Anti-cancer Effect of Bortezomib in Colorectal Cancer Cells.

1620 | Dec 16 2017

Wang S et al. found that the anti-cancer effect of bortezomib and present this novel combinatorial treatment against colorectal cancer. [Read the Full Post]

Synergistic Cytotoxicity of Melatonin and New-generation Anticancer Drugs Against Leukemia Lymphocytes But Not Normal Lymphocytes

1779 | Nov 22 2017

Zhelev Z et al. suggested that melatonin is a promising supplementary component in chemotherapy which allows the therapeutic doses of anticancer drugs to be reduced, minimizing their side-effects. [Read the Full Post]

Inhibition of the Pentose-phosphate Pathway Selectively Sensitizes Leukemia Lymphocytes to Chemotherapeutics by ROS-independent Mechanism

1653 | Nov 21 2017

Zhelev Z et al. suggested that 6-ANA could be used as a supplementary component in anticancer chemotherapy, and would allows therapeutic doses of anticancer drugs to be reduced, thereby minimizing their side-effects. [Read the Full Post]

Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15

0 | Nov 18 2017

Han T et al. proposed that DCAF15 expression may be a useful biomarker to guide clinical trials of this class of drugs, which we refer to as SPLAMs (splicing inhibitor sulfonamides). [Read the Full Post]

Chemotherapy-induced Dkk-1 expression by primary human mesenchymal stem cells is p53 dependent

1731 | Oct 23 2017

Hare I et al. indicated that Dkk-1 has been shown to promote tumor growth in several models of malignancy, suggesting that MSC-derived Dkk-1 could counteract the intent of cytotoxic chemotherapy, and that pharmacologic inhibition of Dkk-1 in patients receiving chemotherapy treatment for certain malignancies may be warranted. [Read the Full Post]

Autophagy-mediated clearance of ubiquitinated mutant huntingtin by graphene oxide

1257 | Sep 10 2017

Jin P et al. revealed a novel biological function of GO and may have implications for developing nanomaterial-based therapeutics for neurodegenerative diseases. [Read the Full Post]

THZ1 targeting CDK7 suppresses STAT transcriptional activity and sensitizes T-cell lymphomas to BCL2 inhibitors

2157 | Aug 09 2017

Cayrol F et al. indicated the combination of THZ1 and the BH3 mimetic obatoclax improves lymphoma growth control in a primary PTCL ex vivo culture and in two STAT3-mutant PTCL xenografts, delineating a potential targeted agent-based therapeutic option for these patients. [Read the Full Post]

Analysis of a cAMP regulated coactivator family reveals an alternative phosphorylation motif for AMPK family members

1709 | Aug 08 2017

Sonntag T et al. suggested that the regulation of cellular targets by AMPK family members is more extensive than previously appreciated. [Read the Full Post]

Bifunctional alkylating agent-mediated MGMT-DNA cross-linking and its proteolytic cleavage in 16HBE cells

0 | Jun 24 2017

Cheng J et al. demonstrated that MGMT might turn into a DNA damage promoter by forming DPC when exposed to HN2. Proteolysis, especially DVC1, plays a crucial role in mDPC repair. [Read the Full Post]

NEDD4L Protein Catalyzes Ubiquitination of PIK3CA Protein and Regulates PI3K-AKT Signaling.

1879 | Jun 08 2017

Wang Z et al. proposed that NEDD4L negatively regulates PIK3CA protein levels via ubiquitination and is required for the maintenance of PI3K-AKT signaling pathway. [Read the Full Post]

Nek2A/SuFu feedback loop regulates Gli-mediated Hedgehog signaling pathway

0 | Jun 07 2017

Zhou F et al. uncovered one of the mechanisms by which Nek2A acts as a modulator of the Hh signaling pathway in the context of a novel negative-feedback loop, which may offer new insights into Gli-mediated Hh signaling regulation in development and human diseases. [Read the Full Post]

Overcoming resistance to TRAIL-induced apoptosis in solid tumor cells by simultaneously targeting death receptors, c-FLIP and IAPs

0 | Jun 03 2017

Huang Y et al. provided a rationale for the development of TRAIL-induced apoptosis-based cancer therapies. [Read the Full Post]

Receptor for Activated C Kinase 1 (RACK1) Promotes Dishevelled Protein Degradation via Autophagy and Antagonizes Wnt Signaling.

1894 | May 02 2017

Cheng M et al reported that receptor for activated C kinase 1 (RACK1) negatively regulates Dishevelled stability and Wnt signaling. RACK1 interacts with Dvl proteins and promotes their lysosomal degradation, and this effect is enhanced by autophagy induction. RACK1 also interacts with LC3 and enhances the association of LC3 with Dvl2, thereby leading to degradation of Dvl proteins through autophagy. These findings reveal a novel regulatory function of RACK1 in Wnt signaling by modulating Dvl stability. [Read the Full Post]

Tetrachlorobenzoquinone induces Nrf2 activation via rapid Bach1 nuclear export/ubiquitination and JNK-P62 signaling

1804 | Apr 21 2017

Su C et al. found that TCBQ-induced activation of Nrf2 involves c-Jun N-terminal kinase (JNK)-P62 signaling. [Read the Full Post]

Lenalidomide, Thalidomide, and Pomalidomide Reactivate the Epstein-Barr Virus Lytic Cycle through Phosphoinositide 3-Kinase Signaling and Ikaros Expression

2122 | Mar 09 2017

Jones RJ et al. concluded LTP may reactivate EBV-positive resting memory B cells thereby enhancing EBV lytic cycle and host immune suppression. [Read the Full Post]

X66, a novel N-terminal heat shock protein 90 inhibitor, exerts antitumor effects without induction of heat shock response

1954 | Feb 25 2017

The HSP90 inhibitory action and the potent antitumor activity, with the anti-HSR action, promise X66 a novel HSP90-targeted agent, which merits further research and development. [Read the Full Post]

Host-based Prophylaxis Successfully Targets Liver Stage Malaria Parasites

2533 | Feb 19 2017

Douglass AN, et al.'s data demonstrate that host-based prophylaxis could be developed into an effective intervention strategy that eliminates LS parasites before the onset of clinical disease and thus opens a [Read the Full Post]

Host-based Prophylaxis Successfully Targets Liver Stage Malaria Parasites

2866 | Jan 08 2017

Douglass AN, et al.‘’s data demonstrate that host-based prophylaxis could be developed into an effective intervention strategy that eliminates LS parasites before the onset of clinical disease and thus opens a new avenue to prevent malaria. [Read the Full Post]

Bifunctional alkylating agent-mediated MGMT-DNA cross-linking and its proteolytic cleavage in 16HBE cells

2722 | Dec 31 2016

Cheng J et al. demonstrated that MGMT might turn into a DNA damage promoter by forming DPC when exposed to HN2. [Read the Full Post]

Overcoming resistance to TRAIL-induced apoptosis in solid tumor cells by simultaneously targeting death receptors, c-FLIP and IAPs

2996 | Nov 01 2016

Huang Y et al. provided a rationale for the development of TRAIL-induced apoptosis-based cancer therapies. [Read the Full Post]

Receptor for Activated C Kinase 1 (RACK1) Promotes Dishevelled Protein Degradation via Autophagy and Antagonizes Wnt Signaling

2277 | Sep 28 2016

Cheng M et al. revealed a novel regulatory function of RACK1 in Wnt signaling by modulating Dvl stability. [Read the Full Post]

ERK induces degradation of tumor suppressor FBW7 in pancreatic cancer

7659 | Mar 18 2015

Ji et al. demonstrated a correlation between low expression of FBW7 and ERK activation in pancreatic cancer. [Read the Full Post]

MiR-146-NF-κB pathway is a key axis in the regulation of FOXP3-deficient prostate cancers

4244 | Mar 12 2015

Liu et al. from University of Alabama at Birmingham reveal FOXP3-microRNA-146(miR-146)-NF-κB axis as a critical signaling pathway in regulating the survival of prostate cancer cells both in vitro and in vivo. [Read the Full Post]

Inhibition of proteasome restores bortesomib-induced thrombocytopenia

10781 | Feb 10 2015

Shi et al. reported clinical proteasome inhibitor enable to block proplatelet formation by megakaryocytes in human and mouse model. [Read the Full Post]

Proteasome inhibitor salvages messense mutated dysferlin in muscular dystrophy patients

4091 | Feb 09 2015

Azakir et al. demonstrated proteasome inhibitor is able to increase the expression of messense mutated dyferlin, and restores the membrane resealing capacity of myoblasts. [Read the Full Post]

Suppressing HER3 signaling by interfering with its Sec61-dependent contranlational translocation

4037 | Feb 03 2015

Ruiz-Saenz et al. demonstrated a novel approach specifically reduces HER3 expression. [Read the Full Post]

The mechanism of action of new antitumor drug FL118

4211 | Dec 25 2014

Recently, Ling et al. demonstrated the mechanism of FL118 antitumor action. The drug suppress tumor growth by promotion of MdmX degradation and consequent stimulation of p53 signaling. [Read the Full Post]

Hippo signaling mediates hypoxia tumorgenesis via SIAH2

4483 | Dec 05 2014

Ma et al. gives a insight into the mechanism of Hippo signaling by investigating the pathway deactivation induced by hypoxia. [Read the Full Post]

Not all DUBs are equal

4046 | Mar 21 2014

Bortezomib (PS-341) is a potent 20S proteasome inhibitor with Ki of 0.6 nM. [Read the Full Post]

MLN9708 is a proteasome inhibitor and is the first to enter clinical trials

3864 | Feb 19 2014

MLN9708 is a selective, orally bioavailable, second-generation proteasome inhibitor. [Read the Full Post]

RO4929097 is a small molecule gamma secretase inhibitor

3755 | Feb 13 2014

RO4929097 is a γ secretase inhibitor with IC50 of 4 nM, inhibiting cellular processing of Aβ40 and Notch with EC50 of 14 nM and 5 nM, respectively. [Read the Full Post]

Bortezomib is the first therapeutic proteasome inhibitor to be tested in humans

3411 | Jan 26 2014

Bortezomib, a boronic acid dipeptide, is a highly selective, reversible inhibitor of the 26S proteasome which primarily functions in the degradation of mis-folded proteins and is essential for the regulation of the cell cycle. [Read the Full Post]

MLN9708 is a proteasome inhibitor and is the first to enter clinical trials as an oral preparation

3342 | Jan 14 2014

MLN9708 immediately hydrolyzed to MLN2238, the biologically active form, on exposure to aqueous solutions or plasma. [Read the Full Post]

Bortezomib is a highly selective reversible inhibitor of the 26S proteasome

3354 | Jan 09 2014

Bortezomib, a boronic acid dipeptide, is a highly selective, reversible inhibitor of the 26S proteasome which primarily functions in the degradation of mis-folded proteins and is essential for the regulation of the cell cycle. [Read the Full Post]

Bortezomib is the first clinically approved proteasome inhibitor for treating multiple human malignancies

3430 | Dec 16 2013

Bortezomib, a boronic acid dipeptide, is a highly selective, reversible inhibitor of the 26S proteasome which primarily functions in the degradation of mis-folded proteins and is essential for the regulation of the cell cycle. [Read the Full Post]

Bortezomib is the first therapeutic proteasome inhibitor

3541 | Nov 26 2013

Bortezomib (PS-341) is a potent 20S proteasome inhibitor with Ki of 0.6 nM. [Read the Full Post]

Semagacestat was compared with placebo in more than 2600 patients

3568 | Oct 21 2013

Semagacestat reduces the secretion of Aβ42, Aβ40 and Aβ38 from H4 human glioma cells stably overexpressing human wild-type APP into the culture medium [Read the Full Post]

PD168393 is a strongly effective EGFR inhibitors

3611 | Jul 18 2013

PD 168393 is docked into the ATP binding pocket of EGFR TK. PD168393 completely suppresses EGF-dependent receptor autophosphorylation in A431 cells during continuous exposure, with continous suppression even after 8 hr in compound-free medium. [Read the Full Post]

MG132 is a specific potent reversible and cell permeable proteasome inhibitor

3308 | Jun 20 2013

MG-132 displays >1000 times more activity than ZLLal in inhibiting the ZLLL-MCA-degrading activity of 20S proteasome with IC50 of 100 nM versus 110 μM. MG-132 also inhibits calpain with IC50 of 1.2 μM. [Read the Full Post]

MG132 is a specific potent reversible and cell permeable proteasome inhibitor

3961 | Apr 22 2013

MG-132 displays >1000 times more activity than ZLLal in inhibiting the ZLLL-MCA-degrading activity of 20S proteasome with IC50 of 100 nM versus 110 μM. MG-132 also inhibits calpain with IC50 of 1.2 μM. MG-132 induces neurite outgrowth in PC12 cells at an optimal concentration of 20 nM. [Read the Full Post]

PS341 was tested in a small Phase I clinical trial on patients with multiple myeloma cancer

2895 | Mar 25 2013

PS-341 is the first therapeutic proteasome inhibitor to be tested in humans. It is approved in the U.S. for treating relapsed multiple myeloma[1] and mantle cell lymphoma. In multiple myeloma, complete clinical responses have been obtained in patients with otherwise refractory or rapidly advancing disease. [Read the Full Post]

DPP 4 is regulated transcriptionally RGS4

3229 | Dec 04 2012

[Read the Full Post]

DPP-4 of cisplatin ECCC involved downregulate

3785 | Nov 02 2012

Th Rho kinase and PI-3-kinase in ECCC completely yet Constantly described. In this study we have tried to determine whether to f HA and CD44 on Rho kinase and PI-3-kinase signaling progression ECCC Interact rdern [Read the Full Post]

BORTEZOMIB: AN INHIBITOR OF PROTEASOMAL DEGRADATION

3017 | Aug 28 2012

BORTEZOMIB Proteasomes are one of the very important small organelles present in the cell. They have an important role in cell cycle regulation by degrading un-necessary proteins present in the cell. Sometimes in cancerous cells, the proteins that play a role in inhibiting un-regulated proliferation of cells are degraded by proteasomes. Inhibition of proteasomes in order to inhibit un-regulated growth is an attractive target in cancer therapy. Different proteasome inhibiting compounds have been used conventionally for the treatment of cancer e.g.,green tea having Epigallocatechin-3-gallate (EGCG), Salinosporamide-A and Disulfiram. Bortezomib is the first proteasomal inhibitor that has got approval for clinical studies for the treatment of cancer. [Read the Full Post]

BORTEZOMIB: AN ANTI-PROTEASOMAL AGENT

4173 | Jul 01 2012

BORTEZOMIB: INTRODUCTION In cell among the tiny organelles proteasomes are the foremost vital ones. They play necessary role in the correct regulation of the cell cycle by removing the proteins that don't seem to be necessary for cell. In cancer cell it rarely happens that the proteins which are involved in the controlling the dysregulated growth of the cells are excised by proteasomes. A promising target for the therapy of cancer is to inhibit proteasomes so that the uncontrolled growth is inhibited. A variety of compounds were typically used for cancer therapy that inhibits proteasomes. Among them EGCG additionally referred to as Epigallocatechin-3-gallate, Disulfiram and Salinosporamide-A that are present in green tea were used. The primary inhibitor of proteasomes that got approved to enter clinical trials for cancer therapy is Bortezomib. [Read the Full Post]

BORTEZOMIB: AN ANTI-PROTEIN DEGRADATION AGENT

5344 | Jun 20 2012

BORTEZOMIB Proteasomes belong to one of the important small organelles present in cell. Cell cycle is regulated by these proteasomes as they remove any unnecessary protein from cell. Usually during the cancer state the proteins which inhibit uncontrolled cell development of cancer are chopped down by these proteasomes. To stop chop these abnormal proteins properly inhibition of proteasomes is necessary which offers a good target for cancer therapy. For cancer treatment a lot of various compounds are being employed that cause proteasomes inhibition for example e.g., green tea having Epigallocatechin-3-gallate (EGCG), Salinosporamide-A and Disulfiram. Bortezomib was entitled to be first inhibitor that got approval to enter clinical studies for treatment of cancer. [Read the Full Post]

BORTEZOMIB; INHIBITING PROTEIN DEGRADATION

4277 | May 17 2012

BORTEZOMIB Poteasomes are one of the very important small organelles present in the cell. They have an important role in cell cycle regulation by degrading un-necessary proteins present in the cell. Sometimes in cancerous cells, the proteins that play a role in inhibiting un-regulated proliferation of cells are degraded by proteasomes. Inhibition of proteasomes in order to inhibit un-regulated growth is an attractive target in cancer therapy. Different proteasome inhibiting compounds have been used conventionally for the treatment of cancer e.g., green tea having Epigallocatechin-3-gallate (EGCG), Salinosporamide-A and Disulfiram. Bortezomib is the first proteasomal inhibitor that has got approval for clinical studies for the treatment of cancer. [Read the Full Post]

BORTEZOMIB – PROTEASOMAL INHIBITOR

3921 | Apr 26 2012

BORTEZOMIB: One of the most important categories of enzymes in the cell is the protein degrading enzymes called as proteosomes. They degrade all types of un-wanted proteins in the cells hence can regulate some important pathways in the cells like gene expression and cell cycle. The compounds which obstruct the activity of these enzymes play an important role in process of inhibition of degradation of cancer inhibiting proteins. Due to these properties proteosome inhibiting molecules like EGCG (Epigallocatechin-3-gallate) known as green tea as well, Disulfiram and Salinosporamide-A have been found to use for treatment of cancer. The first approved proteosomal inhibiting drug for clinical studies is Bortezomib and it is a very famous inhibitor of this class of enzymes. [Read the Full Post]

BORTEZOMIB – A PROTEASOME INHIBITOR

3538 | Apr 10 2012

BORTEZOMIB: There are different enzymes are present in the cell and amongst these enzymes Proteasomes are large enzymes which play function of degrading un-wanted proteins of cells, therefore these enzymes regulate some of the most important pathways including cell cycle and genetic expression. Those compounds which hinder the actions of these proteasomes play important functions in the process of inhibiting the degradation of tumor inhibiting proteins. Because of these properties the proteasome inhibitors such as EGCG (Epigallocatechin-3-gallate) also known as green tea, Salinosporamide-A and Disulfiram have been applied for cancer treatment. Bortezomib is the first approved proteasome inhibitor for clinical trials; this is the most famous inhibitor of this category. [Read the Full Post]

BORTEZOMIB – THE FIRST PROTEASOME INHIBITOR

2962 | Mar 19 2012

Introduction: Inhibition of the Proteasomes In the cellular environment there is a continuous movement of cells through cycles of life and death. Material is up taken and used to create new cells or energy, while protein signaling cascades regulate everything so that the host organism survives. However, during these essential processes proteins become damaged, unraveled or simply surplus to requirements, in this situation there exists clean up mechanisms to recycle as much material as possible. The major (>80%) pathway for this process is the proteasome pathway which in conjunction with the Ubiquitin pathway performs clean up routines in the cellular environment. The proteasome is a tubular protein sealed with another protein containing a tyrosine kinase domain. This tubular protein allows “tagged” protein to enter and bind within the tube section. Then catalytic activity begins to dismantle the protein and pass subunits out into the cytosole for reuse. Protein are recognized for destruction due to the actions of the Ubiquitin protein kinases. [Read the Full Post]