H3B-5942

H3B-5942 is a selective estrogen receptor covalent antagonist (SERCA). It covalently modifies cysteine 530 in the ligand binding domain of wild-type estrogen receptor alpha (ERalpha) and ERalphaY537S. HB-5942 inhibits expression of the ERalpha target genes GREB1 and TFF1 in MCF-7 cells overexpressing wild-type ERalpha (IC50s = 2.74 and 1.3 nM, respectively) or the mutant receptors ERalphaY537S (IC50s = 29.38 and 19.4 nM, respectively), ERalphaY537N (IC50s = 8.14 and 6.1 nM, respectively), ERalphaY537C (IC50s = 12.19 and 9.5 nM, respectively), or ERalphaD538G (IC50s = 24.87 and 4 nM, respectively), which are active independent of estradiol. It inhibits the growth of MCF-7 cells overexpressing wild-type ERalpha or ERalphaY537S (GI50s = 1.3 and 8.3 nM, respectively). H3B-5942 reduces tumor growth in an MCF-7 mouse xenograft model and an ERalphaY537S/WT ST941 patient-derived xenograft (PDX) mouse model in a dose-dependent manner.Formal Name: (2E)-4-[[2-[4-[(1E)-1-(1H-indazol-5-yl)-2-phenyl-1-buten-1-yl]phenoxy]ethyl]amino]-N,N-dimethyl-2-butenamide. CAS Number: 2052128-15-9. Molecular Formula: C31H34N4O2. Formula Weight: 494.6. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 30 mg/ml, DMF:PBS (pH 7.2) (1:3): 0.25 mg/ml, DMSO: 1 mg/ml, Ethanol: 5 mg/ml. lambdamax: 236 nm. SMILES: CC/C(C1=CC=CC=C1)=C(C2=CC=C(C=C2)OCCNC/C=C/C(N(C)C)=O)\C3=CC=C(NN=C4)C4=C3. InChi Code: 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+. InChi Key: BYAUIDXIQATDBT-GIHLFXONSA-N.