Novel vitamin D receptor (VDR) and androgen receptor (AR) ligands with diphenylmethane skeleton

MEDI 78

Shinnosuke Hosoda, ff46027@mail.ecc.u-tokyo.ac.jp1, Aya Tanatani, aya@iam.u-tokyo.ac.jp1, Ken-ichi Wakabayashi1, Kazuo Nagasawa, knaga@cc.tuat.ac.jp2, Hiroyuki Miyachi1, and Yuichi Hashimoto1. (1) Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan, (2) Department of Biotechnology and Life Science, Faculty of Technology, Tokyo University of Agriculture and Technology, 2-24-16, Naka-cho, Koganei, Tokyo, Japan
Nuclear receptors (NRs) regulate the expression of responsive genes and thereby affect diverse processes, including cell growth, development, and metabolism. Numerous field of medicines, including cancer, reproductive biology, and metabolic syndrome are target to NRs. Some natural ligands of NRs have steroidal (or secosteroidal) structure. For example, most of so far known vitamin D receptor (VDR) ligands contain secosteroidal structure, those are unstable to heat and light. Only a few vitamin D agonists, including a bis-phenol derivative LG190178, are known as non-secosteroidal derivatives. Based on these bis-phenol skeletons, we prepared several diphenylmethane derivatives containing nitrogen atom(s). Interestingly, some of these compounds showed specific binding affinity toward not VDR but androgen receptor (AR) selectively, and elicited androgen-antagonistic activity. It means that diphenylmethane skeleton may be a steroid skeleton substitute, which has many advantages over a steroid skeleton. In this presentation, the structure-activity relationships toward VDR and AR will be discussed.