Home Epigenetics Epigenetic Reader Domain inhibitor - NSD inhibitor AZD5153 6-hydroxy-2-naphthoic acid For research use only.

AZD5153 6-hydroxy-2-naphthoic acid

Synonyms: AZD5153 HNT salt

AZD5153 6-hydroxy-2-naphthoic acid (HNT salt) is a potent, selective, and orally available BET/BRD4 bromodomain inhibitor with pKi of 8.3 for BRD4. AZD5153 inhibits the expression of Nuclear receptor binding SET domain protein 3 (NSD3) target genes. NSD3, via H3K36me2, acts as an epigenetic deregulator to facilitate the expression of oncogenesis-promoting genes.

AZD5153 6-hydroxy-2-naphthoic acid Chemical Structure

AZD5153 6-hydroxy-2-naphthoic acid Chemical Structure

CAS No. 1869912-40-2

Purity & Quality Control

AZD5153 6-hydroxy-2-naphthoic acid Related Products

Signaling Pathway

Epigenetic Reader Domain Signaling Pathways

Epigenetic Reader Domain Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HCT116 Function assay 18 hrs Displacement of Halo-tagged histone H3.3 from NanoLuc-tagged full length BRD4 (unknown origin) expressed in HCT116 cells after 18 hrs by NanoBRET assay , IC50 = 0.005 μM. 28195723
HCT116 Function assay 18 hrs Displacement of Halo-tagged histone H3.3 from N-terminal NanoLuc-tagged BRD4 bromodomain 1 (44 to 168 residues) (unknown origin) expressed in HCT116 cells after 18 hrs by NanoBRET assay , IC50 = 1.6 μM. 28195723
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Biological Activity

Description AZD5153 6-hydroxy-2-naphthoic acid (HNT salt) is a potent, selective, and orally available BET/BRD4 bromodomain inhibitor with pKi of 8.3 for BRD4. AZD5153 inhibits the expression of Nuclear receptor binding SET domain protein 3 (NSD3) target genes. NSD3, via H3K36me2, acts as an epigenetic deregulator to facilitate the expression of oncogenesis-promoting genes.
Targets
FL-BRD4 [1]
(Cell-based assay)
5 nM
In vitro
In vitro

Unlike previously described monovalent inhibitors, AZD5153 ligates two bromodomains in BRD4 simultaneously. AZD5153 treatment markedly affects transcriptional programs of MYC, E2F, and mTOR. Of note, mTOR pathway modulation is associated with cell line sensitivity to AZD5153. AZD5153 potently disrupts BRD4 foci in U2OS cells with an IC50 value of 1.7 nmol/L. AZD5153 efficiently downregulates MYC protein levels across the cell line panel irrespective of their sensitivity to AZD5153. AML, MM, and DLBCL cell lines are highly sensitive to AZD5153[1].
Cell Research Cell lines MV-4-11, MM.1S, and K562 cells
Concentrations --
Incubation Time 48 h
Method

Apoptosis was analyzed by flow cytometry using CellEvent Caspase 3/7 Green detection reagent. MV-4-11, MM.1S, and K562 cells were pretreated with AZD5153 or I-BET762 for 48 hours in culture media. Cells were collected and stained with 5 μmol/L final concentration of CellEvent for 30 minutes at 37°C. Flow cytometry was done on a BD Fortessa using the Blue laser and FITC filter set.
Experimental Result Images Methods Biomarkers Images PMID
Western blot NRG1 / BRD4 / GAPDH NRG1 / BRD4 / GAPDH NRG1 / BRD4 / GAPDH BRD4 / C-MYC / GAPDH cle-PARP / cle-caspase3 / GAPDH Wee1 / CDK1 / p-CDK1 / GAPDH 30036377
Growth inhibition assay Tumor Volume / Body Weight 29636547
IHC cle-caspase3 / cle-PARP / Ki-67 31523195
Immunofluorescence CDC6 p-S54 29636547
ELISA IL-10 / IL-12 32184777
In Vivo
In vivo

In vivo administration of AZD5153 leads to tumor stasis or regression in multiple xenograft models of acute myeloid leukemia, multiple myeloma, and diffuse large B-cell lymphoma. AZD5153 modulates MYC and HEXIM1 in AML xenograft tumors and human whole blood[1]. AZD5153 is administered orally to mice bearing MV-4-11 xenografts, and pharmacodynamic activity (intratumoral levels of c-Myc) is measured at 2, 4, and 8 h postdose. A considerable decrease in c-Myc expression is observed out to 8 h post dose at free plasma levels of compound <0.2 μM. This decrease in c-Myc expression after treatment with AZD5153 is consistent with other published BET inhibitors[2].
Animal Research Animal Models Female CB17 SCID and SCID beige mice
Dosages --
Administration by oral gavage mini-pump infusion or s.c
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03205176 Completed
Malignant Solid Tumors|Lymphoma|Ovarian Cancer|Breast Cancer|Pancreatic Cancer|Prostate Cancer
AstraZeneca
 June 30 2017 Phase 1

Chemical Information & Solubility

Molecular Weight 667.75 Formula

C25H33N7O3.C11H8O3
CAS No. 1869912-40-2 SDF --
Smiles CC1C(=O)N(CCN1CCOC2=CC=C(C=C2)C3CCN(CC3)C4=NN5C(=NN=C5OC)C=C4)C.C1=CC2=C(C=CC(=C2)O)C=C1C(=O)O
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 100 mg/mL ( (149.75 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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