GRADE & PURITY ≥98%

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Overview

Information

H3B-5942 is a selective and irreversibleestrogen receptorcovalent antagonist, inactivates both ERα WT and ERα mutation. The Ki values are 1 nM and 0.41 nM, respectively.

Targets

ERα (Y537S) ; ERα WT 0.41 nM(Ki); 1 nM(Ki)

In vitro

H3B-5942 covalently inactivates both wild-type and mutant ERα by targeting Cys530 and enforcing a unique antagonist conformation. Upon binding to ERα, H3B-5942 triggers global DNA binding of ERα to ERE-containing promoter and enhancer regions and induces a transcriptionally repressive conformation of ERα by evicting coactivators. H3B-5942 demonstrates potent antiproliferative activity in a panel of ERα^WT and ERα^MUT lines with GI50 values of 0.5, 2, and 30 nmol/L in the MCF7-Parental, MCF7-LTED-ERα^WT, and MCF7-LTED-ERα^Y537C lines, respectively. In the absence of E2, H3B-5942 shows no significant impact on ER-mediated transcription in the MCF7-Parental (endocrine therapy-sensitive) and MCF7-LTED-ERαY537C lines but does result in a 1.5-fold (P = 0.03) increase in the MCF7-LTED-ERα^WT line. In the presence of E2, H3B-5942 shows a significant dose-dependent decrease in ER-mediated transactivation in all cell lines tested.

In vivo

H3B-5942 demonstrates significant single-agent antitumor activity in xenograft models representing ERαWT and ERαY537S breast cancer.

Specifications

Specifications & Purity

≥98%

Biochemical and Physiological Mechanisms

H3B-5942 is a selective and irreversible estrogen receptor covalent antagonist, inactivates both ERα WT and ERα mutation. The Ki values are 1 nM and 0.41 nM, respectively.

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.

Purity

≥98%

Product Properties

• ALogP: 5.374
• hba_count: 3
• HBD Count: 2
• Rotatable Bond: 11

Names and Identifiers

• Pubchem Sid: 504772999
• Pubchem Sid Url: https://pubchem.ncbi.nlm.nih.gov/substance/504772999
• Canonical Smiles: CCC(=C(C1=CC=C(C=C1)OCCNCC=CC(=O)N(C)C)C2=CC3=C(C=C2)NN=C3)C4=CC=CC=C4
• IUPAC Name: (E)-4-[2-[4-[(E)-1-(1H-indazol-5-yl)-2-phenylbut-1-enyl]phenoxy]ethylamino]-N,N-dimethylbut-2-enamide
• InChIKey: BYAUIDXIQATDBT-GIHLFXONSA-N
• INCHI: 1S/C31H34N4O2/c1-4-28(23-9-6-5-7-10-23)31(25-14-17-29-26(21-25)22-33-34-29)24-12-15-27(16-13-24)37-20-19-32-18-8-11-30(36)35(2)3/h5-17,21-22,32H,4,18-20H2,1-3H3,(H,33,34)/b11-8+,31-28+
• Molecular Weight: 494.63
• Reaxy-Rn: 41100272
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=41100272&ln=

Chemical and Physical Properties

• Solubility: Solubility (25°C) In vitro DMSO: 99 mg/mL (200.14 mM); Ethanol: 13 mg/mL (26.28 mM); Water: Insoluble
• DMSO(mg / mL) Max Solubility: 99
• DMSO(mM) Max Solubility: 200.149606776783
• Water(mg / mL) Max Solubility: ＜1
• Molecular Weight: 494.600 g/mol
• XLogP3: 6.100
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 11
• Exact Mass: 494.268 Da
• Monoisotopic Mass: 494.268 Da
• Topological Polar Surface Area: 70.300 Ų
• Heavy Atom Count: 37
• Formal Charge: 0
• Complexity: 765.000
• 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