H3B-6545 - 10mM in DMSO , CAS No.2052130-80-8

CAS: 2052130-80-8 Cat. No.: H654751 Molecular Weight: 567.58 PubChem CID: 124091040

GRADE & PURITY 10mM in DMSO

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Overview

H3B-6545 is an oral, selective estrogen receptor covalent antagonist ( SERCA ) for the research of metastatic ER-positive, HER2-negative breast cancer

In Vitro

H3B-6545 is a highly selective small molecule that potently antagonizes wild-type and mutant ERα in biochemical and cell based assays. In vitro comparisons with standard of care and other experimental agents confirm increased cell potency of H3B-6545 under continuous as well as washout treatment conditions. H3B-6545, a member of a novel class of ERα antagonists refer to as selective ER covalent antagonist (SERCA), which inactivates both wild-type and mutant ERα by targeting C530 and enforcing a unique antagonist conformation. H3B-6545 is a first-in-class selective ER covalent antagonist (SERCA). H3B-6545 inhibits ERα WT activity and growth of ERα WT -positive breast cancer lines. H3B-6545 potently inhibits ERα WT activity and suppresses proliferation of ERα WT -positive breast cancer lines. With GI 50 s of 0.3-0.4, 1.0, 0.5, 5.2, and 0.2 nM for MCF7, HCC1428, BT483, T47D and CAMA-1 cell lines. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

In vivo, once daily oral dosing of H3B-6545 shows potent activity and superior efficacy to fulvestrant in the MCF-7 xenograft model with maximal antitumor activity at doses >10x below the maximum tolerated dose in mice. In addition, H3B-6545 shows superior antitumor activity to Tamoxifen and Fulvestrant in patient derived xenograft models of estrogen receptor positive breast cancer including models carrying ERα mutations in rat and monkeys, H3B-6545 is well tolerated across a broad dose range and at exposures that significantly exceed those required for efficacy in mouse xenograft models . MCE has not independently confirmed the accuracy of these methods. They are for reference only.

IC50& Target:Estrogen receptor

Specifications

Specifications & Purity

10mM in DMSO

Biochemical and Physiological Mechanisms

H3B-6545 is an oral, selective estrogen receptor covalent antagonist ( SERCA ) for the research of metastatic ER-positive, HER2-negative breast cancer.

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

ANTAGONIST

Names and Identifiers

• PubChem CID: 124091040
• MeSH Entry Terms: ((2E)-N,N-dimethyl-4-((2-((5-((1Z)-4,4,4-trifluoro-1-(3-fluoro-1H-indazol-5-yl)-2-phenylbut-1-en-1-yl)pyridin-2-yl)oxy)ethyl)amino)but-2-enamide) hydrochloride salt;H3B-6545
• Molecular Weight: 567.58