6SZE

RIP2 Kinase Catalytic Domain complex with 5-Amino-1-Phenylpyrazole-4-Carboxamide.

Summary for 6SZE

• Entry DOI: 10.2210/pdb6sze/pdb
• Descriptor: Receptor-interacting serine/threonine-protein kinase 2, 5-Amino-1-Phenylpyrazole-4-Carboxamide, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: fragment based drug design (fbdd), receptor interacting protein 2 kinase, ripk2, rip2k, rip2, structure based drug design (sbdd), transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 71810.46

Authors

Convery, M.A.,Charnley, A.K.,Shewchuk, L. (deposition date: 2019-10-02, release date: 2019-10-23, Last modification date: 2024-05-15)

Primary citation

Haffner, C.D.,Charnley, A.K.,Aquino, C.J.,Casillas, L.,Convery, M.A.,Cox, J.A.,Elban, M.A.,Goodwin, N.C.,Gough, P.J.,Haile, P.A.,Hughes, T.V.,Knapp-Reed, B.,Kreatsoulas, C.,Lakdawala, A.S.,Li, H.,Lian, Y.,Lipshutz, D.,Mehlmann, J.F.,Ouellette, M.,Romano, J.,Shewchuk, L.,Shu, A.,Votta, B.J.,Zhou, H.,Bertin, J.,Marquis, R.W.
Discovery of Pyrazolocarboxamides as Potent and Selective Receptor Interacting Protein 2 (RIP2) Kinase Inhibitors.
Acs Med.Chem.Lett., 10:1518-1523, 2019

PubMed Abstract: Herein we report the discovery of pyrazolocarboxamides as novel, potent, and kinase selective inhibitors of receptor interacting protein 2 kinase (RIP2). Fragment based screening and design principles led to the identification of the inhibitor series, and X-ray crystallography was used to inform key structural changes. Through key substitutions about the N1 and C5 N positions on the pyrazole ring significant kinase selectivity and potency were achieved. Bridged bicyclic pyrazolocarboxamide represents a selective and potent inhibitor of RIP2 and will allow for a more detailed investigation of RIP2 inhibition as a therapeutic target for autoinflammatory disorders.

PubMed: 31749904
DOI: 10.1021/acsmedchemlett.9b00141

Experimental method

X-RAY DIFFRACTION (2.94 Å)