6KZI

Crystal structure of Ser/Thr kinase Pim1 in complex with thioridazine derivatives

Replaces:  4MED

Summary for 6KZI

• Entry DOI: 10.2210/pdb6kzi/pdb
• Descriptor: Serine/threonine-protein kinase pim-1, 4-(2-chloro-10H-phenoxazin-10-yl)-N,N-diethylbutan-1-amine (2 entities in total)
• Functional Keywords: pim1, 10-debc, transferase-inhibitor complex, transferase/inhibitor
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 33637.60

Authors

Zhang, W.,Wan, X.,Li, W.,Xie, Y.,Huang, N. (deposition date: 2019-09-24, release date: 2020-03-04, Last modification date: 2024-11-06)

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

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

Experimental method

X-RAY DIFFRACTION (2.8 Å)