PT-2385
PT2385 is a HIF-2α antagonist with luciferase EC50 of 27 nM and no significant off-target activity.
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包装价格促销价数量
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2mg￥1425.001140.00- +
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5mg￥2062.001650.00- +
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10mg￥3600.002880.00- +
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50mg￥10687.008550.00- +
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100mg￥15487.0012390.00- +
- 货号: ajce49602
- CAS: 1672665-49-4
- 别名:
- 分子式: C17H12F3NO4S
- 分子量: 383.34
- 纯度: ＞98%
- 溶解度: DMSO : ≥ 50 mg/mL (130.43 mM)
- 储存: Store at -20°C
- 库存: 现货
Background
PT2385 is a HIF-2α antagonist with luciferase EC50 of 27 nM and no significant off-target activity.
PT2385 blocks HIF-2α dimerization with the HIF1α/2α transcriptional dimerization partner ARNT/HIF1β. PT2385 inhibits the expression of HIF2α-dependent genes, including VEGF-A, PAI-1, and cyclin D1 in ccRCC cell lines and tumor xenografts. PT2385 has no effect on the proliferation or viability of 786-O and A498 cells in culture at concentration as high as 10 μmol/L. Treatment of 786-O cells with PT2385 significantly reduces the levels of mRNA for CCND1, VEGF-A, GLUT1, and PAI-1 in a concentration-dependent manner. Treatment of Hep3B cells with PT2385 reduces hypoxia-induced expression of erythropoietin (EPO) and PAI-1, both known HIF2α target genes[2].
PT2385 exhibits good mouse oral bioavailability (110%) and low to medium in vivo clearance. In mice administrated via intravenous injection, the t1/2 of PT2385 is 3.3 h. In rat pharmacokinetics studies, the oral bioavailability (F) when dosed at 10 mg/kg is 40% and the t1/2 is 3.3 h. In dogs, the oral bioavailability (F) is 87% and the t1/2 is 11 h[1]. Treatment of tumor-bearing mice with PT2385 causes dramatic tumor regressions (clear cell renal cell carcinomas). PT2385 exhibits no adverse effect on cardiovascular performance[2].
[1] Wehn PM, et al. J Med Chem. 2018, 61(21):9691-9721. [2] Wallace EM, et al. Cancer Res. 2016, 76(18):5491-500.
