H3B-5942

H3B-5942 is a selective, irreversible and orally active estrogen receptor covalent antagonist, inactivates both wild-type and mutant ERα by targeting Cys530, with K_is of 1 nM and 0.41 nM, respectively. H3B-5942 reduces ERα target gene GREB1, shows potent antitumor activity both in multiple cell lines or animals bearing ERα^WT or ERα mutations^[1]. IC50 & Target: Ki: 1 nM (ERα^WT), 0.41 nM (ERα^Y537S)^[1] In Vitro: H3B-5942 is a selective and irreversible estrogen receptor covalent antagonist, inactivates both wild-type and mutant ERα by targeting Cys530, with K_is of 1 nM and 0.41 nM, respectively^[1].
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-ERα^WT, various MCF7-ERαMUT lines, and the PDX-ERα^Y537S/WT line^[1].
H3B-5942 also decreases proliferation of MCF7-Parental, MCF7-LTED-ERα^WT, and MCF7-LTED-ERα^Y537C 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 ERα^WT or clinically frequent ERα mutations^[1]. 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^[1].
H3B-5942 (3, 10, 30, 100, and 200 mg/kg, p.o, q.d.) exhibits similar anti-tumor activity in the ERα^Y537S/WT ST941 model in athymic female nude mice^[1].