7LUK
CRYSTAL STRUCTURE OF RAR-RELATED ORPHAN RECEPTOR C (NHIS-RORGT(244-487)-L6-SRC1(678-692) IN COMPLEX WITH AN AZATRICYCLIC RORGT INVERSE AGONIST
Summary for 7LUK
| Entry DOI | 10.2210/pdb7luk/pdb |
| Descriptor | Nuclear receptor ROR-gamma, (2S)-N-[(6aS,7R,9aS)-9a-[(4-fluorophenyl)sulfonyl]-3-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)-6,6a,7,8,9,9a-hexahydro-5H-cyclopenta[f]quinolin-7-yl]-2-hydroxy-2-methyl-3-(methylsulfonyl)propanamide (3 entities in total) |
| Functional Keywords | rorgt, nuclear hormone receptor, ligand-binding domain, inverse agonist, ransferase-transferase inhibitor complex, transferase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 33565.53 |
| Authors | Sack, J.S. (deposition date: 2021-02-22, release date: 2021-05-12, Last modification date: 2023-10-18) |
| Primary citation | Liu, Q.,Xiao, H.Y.,Batt, D.G.,Xiao, Z.,Zhu, Y.,Yang, M.G.,Li, N.,Yip, S.,Li, P.,Sun, D.,Wu, D.R.,Ruzanov, M.,Sack, J.S.,Weigelt, C.A.,Wang, J.,Li, S.,Shuster, D.J.,Xie, J.H.,Song, Y.,Sherry, T.,Obermeier, M.T.,Fura, A.,Stefanski, K.,Cornelius, G.,Chacko, S.,Khandelwal, P.,Dudhgaonkar, S.,Rudra, A.,Nagar, J.,Murali, V.,Govindarajan, A.,Denton, R.,Zhao, Q.,Meanwell, N.A.,Borzilleri, R.,Dhar, T.G.M. Azatricyclic Inverse Agonists of ROR gamma t That Demonstrate Efficacy in Models of Rheumatoid Arthritis and Psoriasis. Acs Med.Chem.Lett., 12:827-835, 2021 Cited by PubMed Abstract: Structure-activity relationship studies directed toward the replacement of the fused phenyl ring of the lead hexahydrobenzoindole RORγt inverse agonist series represented by with heterocyclic moieties led to the identification of three novel aza analogs -. The hexahydropyrrolo[3,2-]quinoline series (X = N, Y = Z=CH) showed potency and metabolic stability comparable to series but with improved membrane permeability and serum free fraction. This structural modification was applied to the hexahydrocyclopentanaphthalene series , culminating in the discovery of as a potent and selective RORγt inverse agonist with an excellent profile, good pharmacokinetic properties, and biologic-like efficacy in preclinical models of rheumatoid arthritis and psoriasis. PubMed: 34055233DOI: 10.1021/acsmedchemlett.1c00112 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.087 Å) |
Structure validation
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