Mechanisms of MCL-1 Protein Stability Induced by MCL-1 Antagonists in B-Cell Malignancies

• Published in: Clinical cancer research Vol. 29; no. 2; pp. 446 - 457
• Main Authors: Tantawy, Shady I., Sarkar, Aloke, Hubner, Stefan, Tan, Zhi, Wierda, William G., Eldeib, Abdelraouf, Zhang, Shuxing, Kornblau, Steven, Gandhi, Varsha
• Format: Journal Article
• Language: English
• Published: United States 17.01.2023
• Subjects: Antineoplastic Agents - therapeutic use; Apoptosis; Apoptosis Regulatory Proteins; Cell Line, Tumor; Humans; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Myeloid Cell Leukemia Sequence 1 Protein - genetics; Myeloid Cell Leukemia Sequence 1 Protein - metabolism; Protein Stability; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Ubiquitin Thiolesterase - metabolism
• ISSN: 1078-0432; 1557-3265; 1557-3265
• DOI: 10.1158/1078-0432.CCR-22-2088

Several MCL-1 inhibitors (MCL-1i), including AMG-176 and AZD5991, have shown promise in preclinical studies and are being tested for the treatment of hematologic malignancies. A unique feature of these agents is induction and stability of Mcl-1 protein; however, the precise mechanism is unknown. We...