title: A potent and highly efficacious Bcl-2/Bcl-xL inhibitor.
abstract: Our previously reported Bcl-2/Bcl-xL inhibitor, 4, effectively inhibited tumor growth but failed to achieve complete regression in vivo. We have now performed extensive modifications on its pyrrole core structure, which has culminated in the discovery of 32 (BM-1074). Compound 32 binds to Bcl-2 and Bcl-xL proteins with K(i) values of <1 nM and inhibits cancer cell growth with IC50 values of 1-2 nM in four small-cell lung cancer cell lines sensitive to potent and specific Bcl-2/Bcl-xL inhibitors. Compound 32 is capable of achieving rapid, complete, and durable tumor regression in vivo at a well-tolerated dose schedule. Compound 32 is the most potent and efficacious Bcl-2/Bcl-xL inhibitor reported to date.
authors: Comprehensive Cancer Center and Departments of Internal Medicine, Pharmacology and Medicinal Chemistry, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0934, USA.
authors: Angelo
authors: A
authors: Aguilar
authors: Comprehensive Cancer Center and Departments of Internal Medicine, Pharmacology and Medicinal Chemistry, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0934, USA.
authors: Haibin
authors: H
authors: Zhou
authors: Comprehensive Cancer Center and Departments of Internal Medicine, Pharmacology and Medicinal Chemistry, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0934, USA.
authors: Jianfang
authors: J
authors: Chen
authors: Comprehensive Cancer Center and Departments of Internal Medicine, Pharmacology and Medicinal Chemistry, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0934, USA.
authors: Liu
authors: L
authors: Liu
authors: Comprehensive Cancer Center and Departments of Internal Medicine, Pharmacology and Medicinal Chemistry, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0934, USA.
authors: Longchuan
authors: L
authors: Bai
authors: Comprehensive Cancer Center and Departments of Internal Medicine, Pharmacology and Medicinal Chemistry, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0934, USA.
authors: Donna
authors: D
authors: McEachern
authors: Comprehensive Cancer Center and Departments of Internal Medicine, Pharmacology and Medicinal Chemistry, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0934, USA.
authors: Chao-Yie
authors: CY
authors: Yang
authors: Life Sciences Institute, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0934, USA.
authors: Jennifer
authors: J
authors: Meagher
authors: Life Sciences Institute, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0934, USA.
authors: Jeanne
authors: J
authors: Stuckey
authors: Comprehensive Cancer Center and Departments of Internal Medicine, Pharmacology and Medicinal Chemistry, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0934, USA.
authors: Shaomeng
authors: S
authors: Wang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D016513:Mice, SCID; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors*; D051020:bcl-X Protein / Q000037:antagonists & inhibitors*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein