H3B-5942

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

H3B-5942 是一种口服选择性雌激素受体共价拮抗剂 (SERCA)，在体外和体内均表现出有效的 ERα 拮抗剂活性。

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.

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.

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.

H3B5942

Endocrinology/Hormones

Estrogen Receptor/ERR

Estrogen Receptor/ERR

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2052128-15-9

494.639

C31H34N4O2

>98% (HPLC)

In Vitro:?DMSO : 83.33 mg/mL (168.47 mM)

CCC(=C(C1=CC=C(C=C1)OCCNCC=CC(=O)N(C)C)C2=CC3=C(C=C2)NN=C3)C4=CC=CC=C4

(E)-4-((2-(4-((E)-1-(1H-indazol-5-yl)-2-phenylbut-1-en-1-yl)phenoxy)ethyl)amino)-N,N-dimethylbut-2-enamide

(-20℃)

With Ice Pack

≥ 2 years