GSK547

RIPK1抑制剂(IC50=31nM)；在10µM浓度下对371种激酶中的RIPK1具有选择性；在100mg/kg剂量下，可在P48CreKrasG12D进行性PDA原位小鼠模型中增加存活率并减少肿瘤体积和肝转移数量；从接受GSK547治疗的小鼠中分离的肿瘤浸润T细胞的过继转移可防止小鼠原位PDA肿瘤生长；在早期动脉粥样硬化形成的ApoESA/SA小鼠模型中，可降低血浆中TNF-α和IL-1β的水平并减少主动脉窦病变中的巨噬细胞浸润。A RIPK1 inhibitor (IC50 = 31 nM); selective for RIPK1 over a panel of 371 kinases at 10 µM; increases survival and reduces tumor volume and the number of liver metastases in a P48Cre KrasG12D orthotopic mouse model of progressive PDA at 100 mg/kg; adoptive transfer of tumor-infiltrating T cells isolated from GSK547-treated mice protects against orthotopic PDA tumor growth in mice; reduces plasma levels of TNF-α and IL-1β and decreases macrophage infiltration in aortic sinus lesions in an ApoESA/SA mouse model of early-phase atherogenesis.分子式C20H18F2N6O分子量396.4N#CC1=CC(N2CCC(C(N3N=CC[C@@]3([H])C4=CC(F)=CC(F)=C4)=O)CC2)=NC=N1