Myeloid cell leukemia sequence 1 (MCL-1) is an anti-apoptotic member of the BH3 domain-containing proteins. Apoptosis is regulated by complex interactions between pro- and anti-apoptotic proteins in the BCL-2 family. MCL-1 sequesters the pro-apoptotic proteins BAK and BAX and blocks cell death. In contrast, BH3-only proteins bind BCL-2 proteins and release BAK and BAX, leading to cell death. This balance is essential for maintaining homeostasis in the body.1
Increased expression of MCL-1 disrupts this balance and blocks cancer cell death. Overexpression of MCL-1 has been widely reported in hematological malignancies and solid tumors, and is associated with poor prognosis and resistance to treatment. This makes MCL-1 an important therapeutic target.1
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BAK: BCL-2 homologous antagonist killer; BAX: BCL-2-associated X protein; BCL-2: B cell lymphoma 2; BH3: BCL-2 homology domain 3.
1. Xiang W, Yang C-Y, Bai L. MCL-1 inhibition in cancer treatment. Onco Targets Ther. 2018;11:7301-7314.