Myeloid cell leukemia 1 (Mcl-1) is an antiapoptotic member of the Bcl-2 family of proteins that when overexpressed is associated with high tumor grade， poor survival， and resistance to chemotherapy. Mcl-1 is amplified in many human cancers， and knockdown of Mcl-1 using RNAi can lead to apoptosis. Thus， Mcl-1 is a promising cancer target. Here， we describe the discovery of picomolar Mcl-1 inhibitors that cause caspase activation， mitochondrial depolarization， and selective growth inhibition. These compounds represent valuable tools to study the role of Mcl-1 in cancer and serve as useful starting points for the discovery of clinically useful Mcl-1 inhibitors.
Myeloid cell leukemia 1 (Mcl-1) is an antiapoptotic member of the Bcl-2 family of proteins that when overexpressed is associated with high tumor grade， poor survival， and resistance to chemotherapy. Mcl-1 is amplified in many human cancers， and knockdown of Mcl-1 using RNAi can lead to apoptosis. Thus， Mcl-1 is a promising cancer target. Here， we describe the discovery of picomolar Mcl-1 inhibitors that cause caspase activation， mitochondrial depolarization， and selective growth inhibition. These compounds represent valuable tools to study the role of Mcl-1 in cancer and serve as useful starting points for the discovery of clinically useful Mcl-1 inhibitors.
