6FX0

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

Summary for 6FX0

• Entry DOI: 10.2210/pdb6fx0/pdb
• Descriptor: Retinoic acid receptor gamma, 6-[3-(1-adamantyl)-4-oxidanyl-phenyl]naphthalene-2-carboxylic acid, TETRAETHYLENE GLYCOL, ... (4 entities in total)
• Functional Keywords: retinoic ligand complex, drug design, selectivity, agonist, signaling protein
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus: P13631
• Total number of polymer chains: 1
• Total formula weight: 50997.57

Authors

Chantalat, L.,Thoreau, E. (deposition date: 2018-03-08, release date: 2018-05-23, Last modification date: 2024-05-08)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.9 Å)