s63845

Description: S63845 is a potent, selective and high affinity small molecule inhibitor of MCL1 (myeloid cell leukemia 1) with Ki value < 1.2 nM. S63845 potently kills MCL1-dependent cancer cells, including multiple myeloma, leukaemia and lymphoma cells, by activating the BAX/BAK-dependent mitochondrial apoptotic pathway. In vivo, S63845 shows potent anti-tumour activity with an acceptable safety margin as a single agent in several cancers. Moreover, MCL1 inhibition, either alone or in combination with other anti-cancer drugs, proved effective against several solid cancer-derived cell lines. These results point towards MCL1 as a target for the treatment of a wide range of tumours. It is the first high affinity MCL-1 inhibitor with potent in vivo activity, it acts by binding to the BH3-binding groove of MCL-1 with a KD value of 0.19 nM for human MCL-1. S63845 is also highly selective against other BCL family proteins such as BCL-2 (Ki > 10, 000nM) and BCL-XL (Ki > 10, 000nM). S63845 showed the clear-on-target activity killing MCL-1-dependent cancer cells, including multiple myeloma, leukemia and lymphoma cells. It exhibited potent in vivo antitumor activity with an acceptable safety profile as monotherapy in the treatment of several cancer types.

References: Nature. 2016 Oct 27; 538(7626):477-482.

Publications Citing Use of InvivoChem S63845: Seiller et al. Cell Death and Disease ( 2020) 11:316.

S-63845; S 63845; S63845;

Exact Mass: 828.212

Chemical Name: (R)-2-((5-(3-chloro-2-methyl-4-(2-(4-methylpiperazin-1-yl)ethoxy)phenyl)-6-(5-fluorofuran-2-yl)thieno[2, 3-d]pyrimidin-4-yl)oxy)-3-(2-((1-(2, 2, 2-trifluoroethyl)-1H-pyrazol-5-yl)methoxy)phenyl)propanoic acid