BMS986260

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

BMS-986260 是一种选择性、口服生物可利用的 TGFβR1 抑制剂 (IC50 = 1.6 nM)。 BMS-986260 在多种 TGFβ 依赖性细胞测定中表现出功能活性、优异的激酶组选择性、良好的药代动力学特性以及与抗 PD-1 抗体联合在小鼠结直肠癌 (CRC) 模型中的体内疗效。

BMS-986260 is a selective, and orally bioavailable TGFβR1 inhibitor(IC50 = 1.6 nM). BMS-986260?demonstrated functional activity in multiple TGFβ-dependent cellular assays, excellent kinome selectivity, favorable pharmacokinetic properties, and curative in vivo efficacy in combination with anti-PD-1 antibody in murine colorectal cancer (CRC) models.?Since daily dosing of TGFβR1 inhibitors is known to cause class-based cardiovascular (CV) toxicities in preclinical species, a dosing holiday schedule in the anti-PD-1 combination efficacy studies was explored.?An intermittent dosing regimen of 3 days on and 4 days off allowed mitigation of CV toxicities in one month dog and rat toxicology studies and also provided similar efficacy as once daily dosing.

BMS-986260 is a highly potent TGFβR1 inhibitor in both human (Kiapp=0.8 nM) and mouse (Kiapp= 1.4 nM) biochemical assays. BMS-986260 also inhibits TGFβ induced SMAD phosphorylation in NIH3T3 cell line, primary human T cells, and mouse and human whole blood. BMS-986260 inhibits TGF-β mediated induction of regulatory T cell (Treg) by downregulation of FOXP3 expression and a repression of CD25 with an IC50 of 230 nM.

——

——

Others

Other Targets

TGFβR1

——

——

2001559-19-7

382.07

C18H12ClFN6O

>98% (HPLC)

In Vitro:?DMSO : 125 mg/mL (326.56 mM)

OCCn1cnc(c1-c1ccc2ncc(C#N)n2n1)-c1ccc(F)c(Cl)c1

——

(-20℃)

With Ice Pack

≥ 2 years