BI-2852 是基于药物结构设计的 switch SI/II 口袋的 KRAS 抑制剂，其通过基于结构的药物设计具有纳摩尔亲和力。BI-2852 在机理上不同于共价 KRASG12C 抑制剂 (结合 switch II)，它结合存在于 KRAS 的活性和非活性形式中的不同口袋。BI-2852 阻断 GEF，GAP 和效应子与 KRAS 的相互作用，导致下游信号传导的抑制和 KRAS 突变细胞中的抗增殖作用。
货号:ajcx13756
CAS:2375482-51-0
分子式:C31H28N6O2
分子量：516.59
溶解度:DMSO: 55 mg/mL (106.47 mM)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

BI-2852 is a KRAS inhibitor for the switch I/II pocket (SI/II-pocket) by structure-based drug design with nanomolar affinity. BI-2852 is mechanistically distinct from covalent KRASG12C inhibitor (binds to switch II pocket) because it binds to a different pocket present in both the active and inactive forms of KRAS. BI-2852 blocks GEF, GAP, and effector interactions with KRAS, leading to inhibition of downstream signaling and an antiproliferative effect in KRAS mutant cells[1]. KRAS(G12C)|450 nM (IC50)|KRAS(G12C)|750 nM (Kd)

BI-2852 (Compound 1) (10 nM-10 μ 2 hours) shows a dose-dependent pERK modulation and antiproliferative effect at EC50s of 5.8 &#181M and 6.7 &#181M in soft agar and low serum conditions in NCI-H358 cells[1].

参考文献:
[1]. Kessler D, et al. Drugging an undruggable pocket on KRAS. Proc Natl Acad Sci U S A. 2019 Aug 6; 116(32):15823-15829.