5CF8

CRYSTAL STRUCTURE OF JANUS KINASE 2 IN COMPLEX WITH N,N-DICYCLOPROPYL-10-ETHYL-7-[(3-METHOXYPROPYL)AMINO] -3-METHYL-3,5,8,10-TETRAAZATRICYCLO[7.3.0.0,6] DODECA-1(9),2(6),4,7,11-PENTAENE-11-CARBOXAMIDE

Summary for 5CF8

• Entry DOI: 10.2210/pdb5cf8/pdb
• Related: 5CF4 5CF5 5CF6
• Descriptor: Tyrosine-protein kinase JAK2, N,N-dicyclopropyl-4-[(1,5-dimethyl-1H-pyrazol-3-yl)amino]-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (3 entities in total)
• Functional Keywords: kinase, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Endomembrane system ; Peripheral membrane protein : O60674
• Total number of polymer chains: 2
• Total formula weight: 72256.27

Authors

Sack, J.S. (deposition date: 2015-07-08, release date: 2015-08-26, Last modification date: 2024-10-30)

Primary citation

Wan, H.,Schroeder, G.M.,Hart, A.C.,Inghrim, J.,Grebinski, J.,Tokarski, J.S.,Lorenzi, M.V.,You, D.,Mcdevitt, T.,Penhallow, B.,Vuppugalla, R.,Zhang, Y.,Gu, X.,Iyer, R.,Lombardo, L.J.,Trainor, G.L.,Ruepp, S.,Lippy, J.,Blat, Y.,Sack, J.S.,Khan, J.A.,Stefanski, K.,Sleczka, B.,Mathur, A.,Sun, J.H.,Wong, M.K.,Wu, D.R.,Li, P.,Gupta, A.,Arunachalam, P.N.,Pragalathan, B.,Narayanan, S.,K C, N.,Kuppusamy, P.,Purandare, A.V.
Discovery of a Highly Selective JAK2 Inhibitor, BMS-911543, for the Treatment of Myeloproliferative Neoplasms.
Acs Med.Chem.Lett., 6:850-855, 2015

PubMed Abstract: JAK2 kinase inhibitors are a promising new class of agents for the treatment of myeloproliferative neoplasms and have potential for the treatment of other diseases possessing a deregulated JAK2-STAT pathway. X-ray structure and ADME guided refinement of C-4 heterocycles to address metabolic liability present in dialkylthiazole 1 led to the discovery of a clinical candidate, BMS-911543 (11), with excellent kinome selectivity, in vivo PD activity, and safety profile.

PubMed: 26288683
DOI: 10.1021/acsmedchemlett.5b00226

Experimental method

X-RAY DIFFRACTION (1.8 Å)