8USS
IL17A complexed to Compound 7
Summary for 8USS
| Entry DOI | 10.2210/pdb8uss/pdb |
| Descriptor | Interleukin-17A, 4,5-dichloro-N-[(1S)-1-cyclohexyl-2-{[(3S)-5-methyl-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepin-3-yl]amino}-2-oxoethyl]-1H-pyrrole-2-carboxamide, CHLORIDE ION, ... (4 entities in total) |
| Functional Keywords | homodimer, inhibitor, del, cytokine |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 15066.18 |
| Authors | Argiriadi, M.A.,Ramos, A.L. (deposition date: 2023-10-29, release date: 2024-04-03, Last modification date: 2024-10-09) |
| Primary citation | Ramos, A.L.,Goedken, E.R.,Frank, K.E.,Argiriadi, M.A.,Bazzaz, S.,Bian, Z.,Brown, J.T.C.,Centrella, P.A.,Chen, H.J.,Disch, J.S.,Donner, P.L.,Duignan, D.B.,Gikunju, D.,Greszler, S.N.,Guie, M.A.,Habeshian, S.,Hartl, H.E.,Hein, C.D.,Hutchins, C.W.,Jetson, R.,Keefe, A.D.,Khan, H.,Li, H.Q.,Olszewski, A.,Ortiz Cardona, B.J.,Osuma, A.,Panchal, S.C.,Phelan, R.,Qiu, W.,Shotwell, J.B.,Shrestha, A.,Srikumaran, M.,Su, Z.,Sun, C.,Upadhyay, A.K.,Wood, M.D.,Wu, H.,Zhang, R.,Zhang, Y.,Zhao, G.,Zhu, H.,Webster, M.P. Discovery of Small Molecule Interleukin 17A Inhibitors with Novel Binding Mode and Stoichiometry: Optimization of DNA-Encoded Chemical Library Hits to In Vivo Active Compounds. J.Med.Chem., 67:6456-6494, 2024 Cited by PubMed Abstract: Dysregulation of IL17A drives numerous inflammatory and autoimmune disorders with inhibition of IL17A using antibodies proven as an effective treatment. Oral anti-IL17 therapies are an attractive alternative option, and several preclinical small molecule IL17 inhibitors have previously been described. Herein, we report the discovery of a novel class of small molecule IL17A inhibitors, identified via a DNA-encoded chemical library screen, and their subsequent optimization to provide in vivo efficacious inhibitors. These new protein-protein interaction (PPI) inhibitors bind in a previously undescribed mode in the IL17A protein with two copies binding symmetrically to the central cavities of the IL17A homodimer. PubMed: 38574366DOI: 10.1021/acs.jmedchem.3c02397 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.47 Å) |
Structure validation
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