9VNX
Crystal Structure of the mutant ROR gamma LBD With Compound 28
This is a non-PDB format compatible entry.
Summary for 9VNX
| Entry DOI | 10.2210/pdb9vnx/pdb |
| Descriptor | Nuclear receptor ROR-gamma, Nuclear receptor coactivator 1, (2~{R})-~{N}-[5-(5-cyano-6-propan-2-yloxy-pyridin-3-yl)-1-(trifluoromethyl)pyrazol-3-yl]-1-ethanoyl-4-propan-2-ylsulfonyl-piperazine-2-carboxamide, ... (6 entities in total) |
| Functional Keywords | nuclear receptor, agonist, nuclear protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 32347.19 |
| Authors | Akai, S.,Nomura, A.,Yamaguchi, K.,Adachi, T. (deposition date: 2025-07-01, release date: 2025-07-30, Last modification date: 2025-08-27) |
| Primary citation | Fukuda, S.,Ikenogami, T.,Otake, K.,Miwa, S.,Maeda, K.,Yamashita, T.,Inami, T.,Yokota, M.,Lu, Y.,Suma, A.,Hirono, Y.,Ogawa, N.,Inoue, T.,Harada, K.,Yamaguchi, K.,Akai, S.,Nomura, A.,Adachi, T.,Terawaki, T.,Suzukawa, A.,Kitamoto, M.,Tanimoto, M.,Noguchi, T.,Hata, T.,Kawahara, I.,Iwamoto, K.,Kondo, K.,Kitagawa, Y.,Naka, Y.,Crowe, P.,Tao, H.,Fenn, M.,Thacher, S.,Oba, M.,Shiozaki, M. A Concise and Modular Approach to Generate Novel ROR gamma Agonists. J.Med.Chem., 68:15849-15871, 2025 Cited by PubMed Abstract: A variety of RORγ inhibitors have been identified, including clinical compounds such as VTP-43742 and JTE-151. In contrast, RORγ agonists have been less explored and LYC-55716 is, to the best of our knowledge, the sole example reached a human clinical investigation. To generate a novel RORγ agonist, functionality switching from preceding RORγ inhibitors has been considered as a rational strategy. Such reported earlier attempts have been hampered by a loss of physicochemical properties to elevated lipophilicity. Starting from RORγ inhibitors, corresponding agonists were generated virtually to assess their druglike characters. Based on their ligand efficiency and lipophilicity, a cyclic amine carboxylate core was regarded as the best for maintaining favorable physicochemical properties. This scaffold was subjected to final optimization by attaching function-oriented modules retaining druglike properties. After multiparameter optimization, novel selective RORγ agonists were discovered, and their effects were confirmed in a syngeneic mouse model after oral administration. PubMed: 40677142DOI: 10.1021/acs.jmedchem.5c00872 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.93 Å) |
Structure validation
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