H3B-6545 - ≥98% , CAS No.2052130-80-8

CAS: 2052130-80-8 Cat. No.: H646807 Molecular Weight: 567.58 PubChem CID: 124091040

GRADE & PURITY ≥98%

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

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.

Form:Solid

IC50& Target:Estrogen receptor

Specifications

Specifications & Purity

≥98%

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 -20°C

Shipped In

Ice chest + Ice pads

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

Action Type

ANTAGONIST

Purity

≥98%

Names and Identifiers

• Canonical Smiles: CN(C)C(=O)C=CCNCCOC1=NC=C(C=C1)C(=C(CC(F)(F)F)C2=CC=CC=C2)C3=CC4=C(NN=C4C=C3)F
• IUPAC Name: (E)-N,N-dimethyl-4-[2-[5-[(Z)-4,4,4-trifluoro-1-(3-fluoro-2H-indazol-5-yl)-2-phenylbut-1-enyl]pyridin-2-yl]oxyethylamino]but-2-enamide
• InChIKey: JPFTZIJTXCHJNE-HMOQVRKWSA-N
• INCHI: 1S/C30H29F4N5O2/c1-39(2)27(40)9-6-14-35-15-16-41-26-13-11-22(19-36-26)28(21-10-12-25-23(17-21)29(31)38-37-25)24(18-30(32,33)34)20-7-4-3-5-8-20/h3-13,17,19,35H,14-16,18H2,1-2H3,(H,37,38)/b9-6+,28-24-
• 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

Chemical and Physical Properties

• Solubility: DMSO : 100 mg/mL (176.19 mM; Need ultrasonic)
• Molecular Weight: 567.600 g/mol
• XLogP3: 6.300
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 9
• Rotatable Bond Count: 11
• Exact Mass: 567.226 Da
• Monoisotopic Mass: 567.226 Da
• Topological Polar Surface Area: 83.100 Ų
• Heavy Atom Count: 41
• Formal Charge: 0
• Complexity: 906.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 2
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 2
• Covalently-Bonded Unit Count: 1