6L12

Crystal structure of Ser/Thr kinase Pim1 in complex with 10-DEBC derivatives

Summary for 6L12

Entry DOI	10.2210/pdb6l12/pdb
Descriptor	Serine/threonine-protein kinase pim-1, 4-[(2-chloranylphenoxazin-10-yl)methyl]cyclohexan-1-amine (3 entities in total)
Functional Keywords	pim-1 kinase, 10-debc, transferase-inhibitor complex, transferase/inhibitor
Biological source	Homo sapiens (Human)
Total number of polymer chains	1
Total formula weight	33621.56
Authors	Zhang, W.,Xie, Y.,Cao, R.,Huang, N.,Zhou, Y. (deposition date: 2019-09-27, release date: 2020-05-27, Last modification date: 2024-10-23)
Primary citation	Li, G.,Zhang, W.,Xie, Y.,Li, Y.,Cao, R.,Zheng, G.,Huang, N.,Zhou, Y. Structure-Based Optimization of 10-DEBC Derivatives as Potent and Selective Pim-1 Kinase Inhibitors. J.Chem.Inf.Model., 60:3287-3294, 2020 Cited by PubMed Abstract: Pim-1 kinase has been widely regarded as an attractive target for anticancer drugs. Here, we reported our continued efforts in structure-based optimization of compound 10-DEBC, a previously identified micromolar Pim-1 inhibitor. Guided by the Site Identification by Ligand Competitive Saturation (SILCS) method, we quickly obtained a series of 10-DEBC derivatives with significantly improved activity and selectivity. In particular, compound exhibited an IC value of 0.9 nM, as well as 220- and 8-fold selectivity over Pim-2 and Pim-3 kinases, respectively. PubMed: 32407627 DOI: 10.1021/acs.jcim.0c00245 PDB entries with the same primary citation
Experimental method	X-RAY DIFFRACTION (1.87 Å)

Structure validation