AZD-5153 6-hydroxy-2-naphthoic acid - 10mM in DMSO , CAS No.1869912-40-2

CAS: 1869912-40-2 Cat. No.: A407776 Molecular Weight: 667.75

GRADE & PURITY 10mM in DMSO

Synonyms

AZD-5153 HNT salt | 2-​Naphthalenecarboxyli​c acid, 6-​hydroxy-​, compd. with (3R)​-​4-​[2-​[4-​[1-​(3-​methoxy-​1,​2,​4-​triazolo[4,​3-​b]​pyridazin-​6-​yl)​-​4-​piperidinyl]​phenoxy]​ethyl]​-​1,​3-​dimethyl-​2-​piperazinone (1:1)

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Overview

Information

AZD-5153 6-hydroxy-2-naphthoic acid AZD-5153 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. AZD-5153 inhibits the expression of Nuclear receptor binding SET dom
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.

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. 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.
Cell Data

cell lines：BON-1 cells and NCI-H727 cells

Concentrations：--

Incubation Time：48 h

Powder Purity:≥97%

Specifications

Synonyms

AZD-5153 HNT salt | 2-​Naphthalenecarboxyli​c acid, 6-​hydroxy-​, compd. with (3R)​-​4-​[2-​[4-​[1-​(3-​methoxy-​1, ​2, ​4-​triazolo[4, ​3-​b]​pyridazin-​6-​yl)​-​4-​piperidinyl]​phenoxy]​ethyl]​-​1, ​3-​dimethyl-​2-​piperazinone (1:1)

Specifications & Purity

10mM in DMSO

Biochemical and Physiological Mechanisms

AZD-5153 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. AZD-5153 inhibits the expression of Nuclear receptor binding SET domain protein 3 (NSD3) target genes. NSD

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

This product requires cold chain shipping. Ground and other economy services are not available.

Action Type

INHIBITOR

Names and Identifiers

• Isomeric SMILES: C[C@@H]1C(=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
• Alternate CAS: 1869912-39-9
• Molecular Weight: 667.75