6BSK

Human PIM1 kinase in complex with compound 12b

Summary for 6BSK

• Entry DOI: 10.2210/pdb6bsk/pdb
• Descriptor: Serine/threonine-protein kinase pim-1, 1,2-ETHANEDIOL, 4-{6-[6-(propan-2-ylamino)-1H-indazol-1-yl]pyrazin-2-yl}benzoic acid, ... (5 entities in total)
• Functional Keywords: kinase, pim1, inhibitor, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Isoform 2: Cytoplasm. Isoform 1: Cell membrane: P11309
• Total number of polymer chains: 1
• Total formula weight: 32719.01

Authors

Ferguson, A.D. (deposition date: 2017-12-03, release date: 2018-03-21, Last modification date: 2023-10-04)

Primary citation

Gingipalli, L.,Block, M.H.,Bao, L.,Cooke, E.,Dakin, L.A.,Denz, C.R.,Ferguson, A.D.,Johannes, J.W.,Larsen, N.A.,Lyne, P.D.,Pontz, T.W.,Wang, T.,Wu, X.,Wu, A.,Zhang, H.J.,Zheng, X.,Dowling, J.E.,Lamb, M.L.
Discovery of 2,6-disubstituted pyrazine derivatives as inhibitors of CK2 and PIM kinases.
Bioorg. Med. Chem. Lett., 28:1336-1341, 2018

PubMed Abstract: The design and synthesis of a novel series of 2,6-disubstituted pyrazine derivatives as CK2 kinase inhibitors is described. Structure-guided optimization of a 5-substituted-3-thiophene carboxylic acid screening hit (3a) led to the development of a lead compound (12b), which shows inhibition in both enzymatic and cellular assays. Subsequent design and hybridization efforts also led to the unexpected identification of analogs with potent PIM kinase activity (14f).

PubMed: 29559278
DOI: 10.1016/j.bmcl.2018.03.018

Experimental method

X-RAY DIFFRACTION (2.573 Å)