6FX0

Structure-based design of Trifarotene (CD5789), a potent and selective RAR gamma agonist for the treatment of acne

6FX0 の概要

• エントリーDOI: 10.2210/pdb6fx0/pdb
• 分子名称: Retinoic acid receptor gamma, 6-[3-(1-adamantyl)-4-oxidanyl-phenyl]naphthalene-2-carboxylic acid, TETRAETHYLENE GLYCOL, ... (4 entities in total)
• 機能のキーワード: retinoic ligand complex, drug design, selectivity, agonist, signaling protein
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Nucleus: P13631
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 50997.57

構造登録者

Chantalat, L.,Thoreau, E. (登録日: 2018-03-08, 公開日: 2018-05-23, 最終更新日: 2024-05-08)

主引用文献

Thoreau, E.,Arlabosse, J.M.,Bouix-Peter, C.,Chambon, S.,Chantalat, L.,Daver, S.,Dumais, L.,Duvert, G.,Feret, A.,Ouvry, G.,Pascau, J.,Raffin, C.,Rodeville, N.,Soulet, C.,Tabet, S.,Talano, S.,Portal, T.
Structure-based design of Trifarotene (CD5789), a potent and selective RAR gamma agonist for the treatment of acne.
Bioorg. Med. Chem. Lett., 28:1736-1741, 2018

PubMed Abstract: Retinoids have a dominant role in topical acne therapy and to date, only RARβ and RARγ dual agonists have reached the market. Given the tissue distribution of RAR isoforms, it was hypothesized that developing RARγ -selective agonists could yield a new generation of topical acne treatments that would increase safety margins while maintaining the robust efficacy of previous drugs. Structural knowledge derived from the X-ray structure of known γ-selective CD437, suggested the design of a novel triaryl series of agonists which was optimized and ultimately led to the discovery of Trifarotene/CD5789.

PubMed: 29706423
DOI: 10.1016/j.bmcl.2018.04.036

実験手法

X-RAY DIFFRACTION (1.9 Å)