6RN8
RIP2 Kinase Catalytic Domain complex with 2(4[(1,3benzothiazol5yl)amino]6(2methylpropane2sulfonyl)quinazolin7yl)oxy)ethyl phosphate
Summary for 6RN8
| Entry DOI | 10.2210/pdb6rn8/pdb |
| Descriptor | Receptor-interacting serine/threonine-protein kinase 2, 2-[4-(1,3-benzothiazol-5-ylamino)-6-~{tert}-butylsulfonyl-quinazolin-7-yl]oxyethyl dihydrogen phosphate, CALCIUM ION, ... (4 entities in total) |
| Functional Keywords | kinase, structure based drug discovery, transferase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 72483.10 |
| Authors | Convery, M.A.,Haile, P.A. (deposition date: 2019-05-08, release date: 2019-07-17, Last modification date: 2024-01-24) |
| Primary citation | Haile, P.A.,Casillas, L.N.,Votta, B.J.,Wang, G.Z.,Charnley, A.K.,Dong, X.,Bury, M.J.,Romano, J.J.,Mehlmann, J.F.,King, B.W.,Erhard, K.F.,Hanning, C.R.,Lipshutz, D.B.,Desai, B.M.,Capriotti, C.A.,Schaeffer, M.C.,Berger, S.B.,Mahajan, M.K.,Reilly, M.A.,Nagilla, R.,Rivera, E.J.,Sun, H.H.,Kenna, J.K.,Beal, A.M.,Ouellette, M.T.,Kelly, M.,Stemp, G.,Convery, M.A.,Vossenkamper, A.,MacDonald, T.T.,Gough, P.J.,Bertin, J.,Marquis, R.W. Discovery of a First-in-Class Receptor Interacting Protein 2 (RIP2) Kinase Specific Clinical Candidate, 2-((4-(Benzo[d]thiazol-5-ylamino)-6-(tert-butylsulfonyl)quinazolin-7-yl)oxy)ethyl Dihydrogen Phosphate, for the Treatment of Inflammatory Diseases. J.Med.Chem., 62:6482-6494, 2019 Cited by PubMed Abstract: RIP2 kinase has been identified as a key signal transduction partner in the NOD2 pathway contributing to a variety of human pathologies, including immune-mediated inflammatory diseases. Small-molecule inhibitors of RIP2 kinase or its signaling partners on the NOD2 pathway that are suitable for advancement into the clinic have yet to be described. Herein, we report our discovery and profile of the prodrug clinical compound, inhibitor , currently in phase 1 clinical studies. Compound potently binds to RIP2 kinase with good kinase specificity and has excellent activity in blocking many proinflammatory cytokine responses in vivo and in human IBD explant samples. The highly favorable physicochemical and ADMET properties of combined with high potency led to a predicted low oral dose in humans. PubMed: 31265286DOI: 10.1021/acs.jmedchem.9b00575 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.69 Å) |
Structure validation
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