raf mutant-in-1

RAF mutant-IN-1 is an inhibitor of RAF kinase(IC50 values of 21 nM, 30 nM and 392 nM for C-RAF 340D/Y341D, B-RAFV600E and B-RAFWT, respectively).

Rineterkib hydrochloride (compound B) is an orally active RAF and ERK1/2 inhibitor in the treatment of a proliferative disease characterized by activating mutations in the MAPK pathway. The activity is particularly related to the treatment of KRAS-mutant NSCLC, BRAF-mutant NSCLC, KRAS-mutant pancreatic cancer, KRAS-mutant colorectal cancer (CRC) and KRAS-mutant ovarian cancer[1]. ERK-IN-1 (compound B) (50, 75 mg/kg, p.o., qd/q2d, 27 days) treatment significantly reduces the tumor volume in the Calu-6 human NSCLC subcutaneous tumor xenograft model in mice[1]. [1]. CAPONIGRO, et al. THERAPEUTIC COMBINATIONS COMPRISING A RAF INHIBITOR AND A ERK INHIBITOR. WO2018051306A1.

Pan-RAS-IN-2（compound 6A）是一种具有口服活性的分子胶，通过诱导环孢素 A（CYPA）、RAS 及处于 ON 状态的 RAS 形成三元复合物来靶向 RAS，在 AsPC-1 细胞中以 IC50 为 0.3 nM 的效力显著抑制下游 RAF 结合及 pERK 信号。Pan-RAS-IN-2 在 RAS 突变型肿瘤细胞系中表现出强抗增殖作用，PSI-7409 tetrasodium 在结直肠癌和胰腺癌靶向治疗研究中有重要应用价值。