Myeloid cell leukemia 1 apoptosis regulator (MCL1)

Myeloid cell leukemia 1 apoptosis regulator (MCL1) is an anti-apoptotic member of the Bcl-2 protein family that plays a central role in regulating cell death, particularly by binding and inactivating pro-apoptotic BH3-only proteins, such as BIM, NOXA, and BAK, at the mitochondria [1][3][7][10]. MCL1 maintains cell viability and mitochondrial integrity, participates in cell cycle regulation, autophagy, and DNA damage response, and is a key determinant of cell fate in numerous physiological and pathological contexts [3][5][9][10]. The MCL1 gene encodes multiple isoforms via alternative splicing, including a canonical long form that is anti-apoptotic (MCL-1L) and short forms (MCL-1S and MCL-1ES) with pro-apoptotic or cell death-inducing properties [7]. Its rapid turnover and regulation through post-translational modifications make it highly responsive to cellular stress and signaling [7][9][10]. Pathologically, overexpression or dysregulation of MCL1 contributes to tumor cell survival, therapeutic resistance (notably in leukemia, lymphoma, and solid tumors), and poor clinical outcomes, making it a validated and actively targeted molecule in cancer therapy [1][5][8]. Multiple small-molecule inhibitors aiming to disrupt its BH3-binding groove are in clinical development for oncology indications [1][5]. Safety and efficacy are active areas of investigation due to MCL1's essential role in the survival of both malignant and normal cells [1].

Other names

Induced myeloid leukemia cell differentiation protein Mcl-1BCL2-related protein A1Mcl-1MCL-1L (long isoform)MCL-1S (short isoform)MCL-1ES (extra short isoform)

Small-molecule inhibitor binding to the BH3-binding groove, BH3 mimetics displacing pro-apoptotic proteins, Inducing apoptosis via mitochondrial outer membrane permeabilization (MOMP)