H3B-5942

SKU: orb1225733

Description

H3B-5942 is an orally available, selective estrogen receptor covalent antagonist (SERCA), demonstrates potent ERαantagonist activity in vitro and in vivo; covalently inactivates both wild-type and mutant ERα by targeting Cys530 and enforcing a unique antagonist conformation; demonstrated significant single-agent antitumor activity in xenograft models representing ERαWT and ERα Y537S breast cancer that was superior to fulvestrant.

Key Properties

• CAS Number: 2052128-15-9
• MW: 494.639
• Purity: >98% (HPLC)
• Formula: C₃₁H₃₄N₄O₂
• 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
• Target: Estrogen Receptor/ERR
• Solubility: In Vitro: DMSO : 83.33 mg/mL (168.47 mM)

Bioactivity

• In Vivo:
  H3B-5942 (1, 3, 10, or 30 mg/kg, p. o, q. d. for 17 days) dose-dependently inhibits tumor growth in MCF7 xenograft model in athymic female nude mice. H3B-5942 (3, 10, 30, 100, and 200 mg/kg, p. o, q. d.) exhibits similar anti-tumor activity in the ERαY537S/WT ST941 model in athymic female nude mice. Animal model: MCF7 xenograft model in athymic female nude mice. Dosage: 1, 3, 10, or 30 mg/kg. Administration: p.o. once a day (q. d. ×1) for 17 days. Result: Exhibited tumor growth inhibition (TGI) on day 17 of 19%, 41%, 68%, and 83%, respectively.
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• In Vitro:
  H3B-5942 is a selective and irreversible estrogen receptor covalent antagonist, inactivates both wild-type and mutant ERα by targeting Cys530, with Kis of 1 nM and 0.41 nM, respectively. H3B-5942 elevates ERα protein level distinct from SERMs/SERD, blocks ERα-dependent transcription in breast cancer cells. H3B-5942 (0.01-10 μM) reduces ERα target gene GREB1 in MCF7-ERαWT, various MCF7-ERαMUT lines, and the PDX-ERαY537S/WT line. H3B-5942 also decreases proliferation of MCF7-Parental, MCF7-LTED-ERαWT, and MCF7-LTED-ERαY537C lines with GI50s of 0.5, 2, and 30 nM, respectively. H3B-5942 (10-25 nM) in combination with CDK4/6 inhibitors (≥25 pM) has synergic inhibitory effect on multiple cell lines bearing ERαWT or clinically frequent ERα mutations.
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Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

H3B5942

Quick Database Links

Gene Symbol

Estrogen Receptor/ERR