1. Discovery and in Vivo Evaluation of Macrocyclic Mcl-1 Inhibitors Featuring an α-Hydroxy Phenylacetic Acid Pharmacophore or Bioisostere
- Author
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Gwenaella Rescourio, Ana Z. Gonzalez, Salman Jabri, Brian Belmontes, Gordon Moody, Doug Whittington, Xin Huang, Sean Caenepeel, Mario Cardozo, Alan C. Cheng, David Chow, Hannah Dou, Adrie Jones, Ron C. Kelly, Yihong Li, Mike Lizarzaburu, Mei-Chu Lo, Rommel Mallari, Cesar Meleza, Yosup Rew, Scott Simonovich, Daqing Sun, Simon Turcotte, Xuelei Yan, Simon G. Wong, Evelyn Yanez, Manuel Zancanella, Jonathan Houze, Julio C. Medina, Paul E. Hughes, and Sean P. Brown more...
- Subjects
Sulfonamides ,Administration, Oral ,Biological Availability ,Mice, Nude ,Antineoplastic Agents ,Hydrogen Bonding ,Crystallography, X-Ray ,Xenograft Model Antitumor Assays ,Rats, Sprague-Dawley ,Structure-Activity Relationship ,Drug Stability ,Cell Line, Tumor ,Drug Design ,Drug Discovery ,Animals ,Humans ,Myeloid Cell Leukemia Sequence 1 Protein ,Molecular Medicine ,Female ,Multiple Myeloma ,Phenylacetates - Abstract
Overexpression of the antiapoptotic protein Mcl-1 provides a survival advantage to some cancer cells, making inhibition of this protein an attractive therapeutic target for the treatment of certain types of tumors. Herein, we report our efforts toward the identification of a novel series of macrocyclic Mcl-1 inhibitors featuring an α-hydroxy phenylacetic acid pharmacophore or bioisostere. This work led to the discovery of more...
- Published
- 2019
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