H3B-5942

SKU: orb1301635

Description

H3B-5942 is a selective estrogen receptor covalent antagonist (SERCA) that irreversibly targets ERα. It is a research tool used in vitro and in vivo to study endocrine-resistant breast cancer models and investigate novel therapeutic strategies for ER-positive malignancies.

Research Area

Metabolism Research

Key Properties

• CAS Number: 2052128-15-9
• MW: 494.63
• Purity: 99.21% (May vary between batches)
• Formula: C₃₁H₃₄N₄O₂
• SMILES: CC\C(=C(\c1ccc(OCCNC\C=C\C(=O)N(C)C)cc1)c1ccc2[nH]ncc2c1)c1ccccc1
• Target: Estrogen/progestogen Receptor,Estrogen Receptor/ERR
• Solubility: DMSO:50 mg/mL (101.09 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.04 mM)

Bioactivity

• Target IC50:
  Erα (Y537S):0.41 nM (Ki)|Erα (WT):1 nM (Ki)
• In Vivo:
  Single or repeat dosing of H3B-5942 at 200 mg/kg suppressed a large panel of direct ERα target genes, with q.d.×1 dosing maintaining target gene suppression for up to 72 hours after dose, and q.d.×3 (3 daily doses) dosing demonstrating greatest suppression in PGR and NPY1R .
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• In Vitro:
  H3B-5942 dosed once (q.d.×1) orally at 30 to 300 mg/kg showed a dose-proportional increase in plasma and tumor exposure and a concomitant dose-proportional decrease in expression of the ERα target genes PGR and NPY1R in the ERαY537S/WT ST941 tumor model. Single or repeat dosing of H3B-5942 at 200 mg/kg suppressed a large panel of direct ERα target genes, with q.d.×1 dosing maintaining target gene suppression for up to 72 hours after dose, and q.d.×3 (3 daily doses) dosing demonstrating greatest suppression in PGR and NPY1R
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• Animal Research:
  Animals were selected based on TV and randomized into treatment groups of 6 to 8 animals per group. Single-agent or combination treatments were started on day 0 and continued for the duration of the study. H3B-5942 was administered orally, tamoxifen was given Q2D, fulvestrant was given , and palbociclib was administered orally Each treatment was administered based on BW (10 mL/kg). H3B-5942 was formulated daily in 10% 2-Hydroxypropyl-β-CycloDextrin (HPβCD) in 5% dextrose, tamoxifen was formulated in 95% peanut oil/5% ethanol (EtOH), clinical-grade fulvestrant was administered, and palbociclib was formulated in 25 mmol/L sodium bicarbonate, 15 mmol/L lactic acid solution with 2% Cremophor EL. The BW measurements were performed daily, and tumor measurements were recorded twice a week.
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Storage & Handling

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

Alternative Names

EstrogenReceptor, Estrogen Receptor/ERR, H3B 5942, H3B5942, H-3B-5942, H3B-5942, Estrogen Receptor, ERα, ERR, inhibit, Inhibitor, progestogenReceptor, progestogen Receptor

Compound Identifiers

PubChem CID

124091011