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1. Discovery of Mcl-1-specific inhibitor AZD5991 and preclinical activity in multiple myeloma and acute myeloid leukemia

Author

Adriana E. Tron, Matthew A. Belmonte, Ammar Adam, Brian M. Aquila, Lawrence H. Boise, Elisabetta Chiarparin, Justin Cidado, Kevin J. Embrey, Eric Gangl, Francis D. Gibbons, Gareth P. Gregory, David Hargreaves, J. Adam Hendricks, Jeffrey W. Johannes, Ricky W. Johnstone, Steven L. Kazmirski, Jason G. Kettle, Michelle L. Lamb, Shannon M. Matulis, Ajay K. Nooka, Martin J. Packer, Bo Peng, Philip B. Rawlins, Daniel W. Robbins, Alwin G. Schuller, Nancy Su, Wenzhan Yang, Qing Ye, Xiaolan Zheng, J. Paul Secrist, Edwin A. Clark, David M. Wilson, Stephen E. Fawell, and Alexander W. Hird

Subjects
Science
Abstract

High expression of Mcl-1 promotes tumorigenesis and resistance to anticancer therapies. Here they report a macrocyclic molecule with high selectivity and affinity for Mcl-1 that exhibits potent anti-tumor effects as single agent and in combination with bortezomib or venetoclax in preclinical models of multiple myeloma and acute myeloid leukemia.

Published
2018
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