SAR439859(compound43d)是一种具有口服活性，非甾体和选择性雌激素受体降解剂(SERD)。SAR439859是一种有效的ER拮抗剂，具有ER降解活性，EC50为0.2nM。SAR439859可在ER+乳腺癌中表现出强大的抗肿瘤功效和有限的交叉耐药性。
货号:ajcx31450
CAS:2114339-57-8
分子式:C31H30Cl2FNO3
分子量：554.48
溶解度:DMSO: 125 mg/mL (225.44 mM)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

SAR439859 (compound 43d) is an orally active, nonsteroidal and selective estrogen receptor degrader (SERD). SAR439859 is a potent ER antagonist and has ER degrading activity with an EC50 of 0.2 nM for ERα degradation[1]. SAR439859 demonstrates robust antitumor efficacy and limited cross-resistance in ER+ breast cancer[2].

SAR439859 (compound 43d) induces strong in vivo antitumor activity against a variety of BC cell lines and patient-derived xenografts, including models that harbor ERα mutations[1].

SAR439859 (compound 43d; orally; 2.5-25 mg/kg; twice daily for 30 days) exhibits substantial tumor-growth inhibition and displays tumor regression at the dose of 25 mg/kg/BID[1]. SAR439859 (3 mg/kg for iv and 10 mg/kg for po) shows a low to moderate clearance in the three animal species tested (0.03-1.92 L/h•kg), low to moderate volume of distribution (Vss=0.5-6.1 L/kg), and good bioavailability (54-76%) across species. It is noticed that T1/2 was variable across species (1.98 h in mouse, 4.13 h in rat and 9.80 h in dog)[1]. Animal Model: Nu/nu mouse with MCF7 tumor xenograft model[1]

[1]. El-Ahmad Y, et al. Discovery of 6-(2,4-Dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylic acid (SAR439859), a Potent and Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen-Receptor-Positive Breast Cancer. J Med Chem. 2019 Nov 27. [2]. Monsif Bouaboula, et al. Abstract 943: SAR439859, an orally bioavailable selective estrogen receptor degrader (SERD) that demonstrates robust antitumor efficacy and limited cross-resistance in ER+ breast cancer.