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Formula | C40H57N5O7 |
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Molecular Weight | 719.91 | CAS No. | 868540-17-4 | |
Solubility (25°C)* | In vitro | DMSO | 100 mg/mL (138.9 mM) | |
Water | Insoluble | |||
Ethanol | Insoluble | |||
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.) |
Description | Carfilzomib (PR-171) is an irreversible proteasome inhibitor with IC50 of <5 nM in ANBL-6 cells, displayed preferential in vitro inhibitory potency against the ChT-L activity in the β5 subunit, but little or no effect on the PGPH and T-L activities. Carfilzomib activates prosurvival autophagy and induces cell apoptosis. | ||
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In vitro | Carfilzomib inhibits proliferation in a variety of cell lines and patient-derived neoplastic cells, including multiple myeloma, and induced intrinsic and extrinsic apoptotic signaling pathways and activation of c-Jun-N-terminal kinase (JNK). Carfilzomib reveals enhanced anti-MM activity, overcome resistance to other agents, and acts synergistically with (Dex). Carfilzomib shoes preferential in vitro inhibitory potency against the ChT-L activity in the β5 subunit, with over 80% inhibition at doses of 10 nM. Short exposure to low-dose Carfilzomib leads to preferential binding specificity for the β5 constitutive 20S proteasome and the β5i immunoproteasome subunits. Measurement of caspase activity in ANBL-6 cells pulsed with Carfilzomib reveals substantial increases in caspase-8, caspase-9, and caspase-3 activity after 8 hours, giving a 3.2-, 3.9- and 6.9-fold increase, respectively, over control cells after 8 hours. In carfilzomib pulse-treated cells, the mitochondrial membrane integrity is decreased to 41% (Q1 + Q2), compared with 75% in vehicle-treated control cells. [1] In another study, Carfilzomib has also shown preclinical effectiveness against hematological and solid malignancies. [2] Carfilzomib directly inhibits osteoclasts formation and bone resorption. [3] |
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In vivo | Carfilzomib moderately reduces tumor growth in an in vivo xenograft model. Carfilzomib effectively decreases multiple myeloma cell viability following continual or transient treatment mimicking. Carfilzomib increases trabecular bone volume, decreases bone resorption and enhances bone formation in non-tumor bearing mice. [3] |
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Data from [Data independently produced by Sci Transl Med, 2014, 6(250), 250ra112]
Data from [Cancer Res, 2014, 74(16), 4458-69]
Data from [J Virol, 2013, 87(23), 13035-41]
Data from [Data independently produced by , , Clin Cancer Res, 2017, 23(16):4817-4830]
Stress response silencing by an E3 ligase mutated in neurodegeneration [ Nature, 2024, 626(8000):874-880] | PubMed: 38297121 |
Proteasome inhibition enhances the anti-leukemic efficacy of chimeric antigen receptor (CAR) expressing NK cells against acute myeloid leukemia [ J Hematol Oncol, 2024, 17(1):85] | PubMed: 39285441 |
Simultaneous proteome localization and turnover analysis reveals spatiotemporal features of protein homeostasis disruptions [ Nat Commun, 2024, 15(1):2207] | PubMed: 38467653 |
The molecular dissection of TRIM25's RNA-binding mechanism provides key insights into its antiviral activity [ Nat Commun, 2024, 15(1):8485] | PubMed: 39353916 |
FNDC4 alleviates cardiac ischemia/reperfusion injury through facilitating HIF1α-dependent cardiomyocyte survival and angiogenesis in male mice [ Nat Commun, 2024, 15(1):9667] | PubMed: 39516487 |
A structure-based designed small molecule depletes hRpn13Pru and a select group of KEN box proteins [ Nat Commun, 2024, 15(1):2485] | PubMed: 38509117 |
Development of an orally bioavailable CDK12/13 degrader and induction of synthetic lethality with AKT pathway inhibition [ Cell Rep Med, 2024, 5(10):101752] | PubMed: 39353441 |
MUC20 regulated by extrachromosomal circular DNA attenuates proteasome inhibitor resistance of multiple myeloma by modulating cuproptosis [ J Exp Clin Cancer Res, 2024, 43(1):68] | PubMed: 38439082 |
Propafenone facilitates mitochondrial-associated ferroptosis and synergizes with immunotherapy in melanoma [ J Immunother Cancer, 2024, 12(11)e009805] | PubMed: 39581704 |
Dihydrolipoamide dehydrogenase (DLD) is a novel molecular target of bortezomib [ Cell Death Dis, 2024, 15(8):588] | PubMed: 39138149 |
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Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.
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