Modeling, Synthesis and Biological Evaluation of Potential Retinoid X Receptor-Selective Agonists: Novel Halogenated Analogues of 4-[1-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic Acid (Bexarotene) (pages 1551–1566)
Julie K. Furmick, Dr. Ichiro Kaneko, Angela N. Walsh, Joanna Yang, Jaskaran S. Bhogal, Geoffrey M. Gray, Juan C. Baso, Drew O. Browder, Jessica L. S. Prentice, Luis A. Montano, Chanh C. Huynh, Lisa M. Marcus, Dorian G. Tsosie, Jungeun S. Kwon, Alexis Quezada, Nicole M. Reyes, Brittney Lemming, Puneet Saini, Dr. Arjan van der Vaart, Dr. Thomas L. Groy, Dr. Pamela A. Marshall, Dr. Peter W. Jurutka and Dr. Carl E. Wagner
Article first published online: 23 AUG 2012 | DOI: 10.1002/cmdc.201200319
Transcriptional signaling: An analogue of bexarotene with two fluorine atoms ortho to the carboxylic acid group has a lower EC50 value (34 nM) than bexarotene (55 nM) for the retinoid X receptor in HCT-116 cells. A low-energy docked conformation of the difluorobexarotene analogue in the ligand binding pocket of RXR as modeled in AutoDock 4.2 is shown.