Discovery of A-1331852, a First-in-Class, Potent, and Orally-Bioavailable BCL-X<sub>L</sub> Inhibitor
Le Wang, George Doherty, Andrew S. Judd, Zhi‐Fu Tao, Terkel Hansen, Robin R. Frey, Xiaohong Song, Milan Bruncko, Aaron Kunzer, Xilu Wang, Michael Wendt, John A. Flygare, Nathaniel D. Catron, Russell A. Judge, Chang H. Park, Shashank Shekhar, Darren C. Phillips, Paul Nimmer, Morey L. Smith, Stephen K. Tahir, Xiao Yu, John Xue, Haichao Zhang, Phuong N. Le, Michael J. Mitten, Erwin R. Boghaert, Wenqing Gao, Peter Kovar, Edna F. Choo, Dolores Diaz, Wayne J. Fairbrother, Steven W. Elmore, Deepak Sampath, Joel D. Leverson, Andrew J. Souers
Abstract
. A-1331852 has since been used as a critical tool molecule for further exploring BCL-2 family protein biology, while also representing an attractive entry into a drug discovery program.
Topics & Concepts
PharmacophoreDrug discoveryComputational biologyChemistrySmall moleculeKey (lock)Inhibitor of apoptosisVirtual screeningOrally activeApoptosisStereochemistryComputer scienceBiochemistryBiologyProgrammed cell deathIn vitroComputer securityCell death mechanisms and regulationProtein Degradation and InhibitorsSignaling Pathways in Disease