5AYG

Crystal Structure of the Human ROR gamma Ligand Binding Domain With 3g

Summary for 5AYG

• Entry DOI: 10.2210/pdb5ayg/pdb
• Descriptor: Nuclear receptor ROR-gamma, 3-[5-(2-cyclohexylethyl)-4-ethyl-1,2,4-triazol-3-yl]-N-naphthalen-1-yl-propanamide (3 entities in total)
• Functional Keywords: inhibitor, complex, nuclear receptor, dna binding protein-inhibitor complex, dna binding protein/inhibitor
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 60606.13

Authors

Noguchi, M.,Doi, S.,Nomura, A.,Kikuwaka, M.,Murase, K.,Hirata, K.,Kamada, M.,Adachi, T. (deposition date: 2015-08-20, release date: 2016-03-02, Last modification date: 2023-11-08)

Primary citation

Hirata, K.,Kotoku, M.,Seki, N.,Maeba, T.,Maeda, K.,Hirashima, S.,Sakai, T.,Obika, S.,Hori, A.,Hase, Y.,Yamaguchi, T.,Katsuda, Y.,Hata, T.,Miyagawa, N.,Arita, K.,Nomura, Y.,Asahina, K.,Aratsu, Y.,Kamada, M.,Adachi, T.,Noguchi, M.,Doi, S.,Crowe, P.,Bradley, E.,Steensma, R.,Tao, H.,Fenn, M.,Babine, R.,Li, X.,Thacher, S.,Hashimoto, H.,Shiozaki, M.
SAR Exploration Guided by LE and Fsp(3): Discovery of a Selective and Orally Efficacious ROR gamma Inhibitor
Acs Med.Chem.Lett., 7:23-27, 2016

PubMed Abstract: A novel series of RORγ inhibitors was identified starting with the HTS hit 1. After SAR investigation based on a prospective consideration of two drug-likeness metrics, ligand efficiency (LE) and fraction of sp(3) carbon atoms (Fsp(3)), significant improvement of metabolic stability as well as reduction of CYP inhibition was observed, which finally led to discovery of a selective and orally efficacious RORγ inhibitor 3z.

PubMed: 26819660
DOI: 10.1021/acsmedchemlett.5b00253

Experimental method

X-RAY DIFFRACTION (2.6 Å)