7XSV

Crystal Structures of PIM1 in Complex with Macrocyclic Compound H3

Summary for 7XSV

• Entry DOI: 10.2210/pdb7xsv/pdb
• Descriptor: Serine/threonine-protein kinase pim-1, 8-Methyl-2,5,20-trioxa-8,13,17-triazatetracyclo[11.10.2.014,19.021,25]pentacosa-1(24),14(19),15,17,21(25),22-hexaene (3 entities in total)
• Functional Keywords: pim-1 kinase, compound h3, transferase-inhibitor complex, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 33648.15

Authors

Shen, C.,Xie, Y.,Ren, X.,Zhou, Y.,Niu, H. (deposition date: 2022-05-15, release date: 2022-07-13, Last modification date: 2023-11-29)

Primary citation

Xu, J.,Shen, C.,Xie, Y.,Qiu, B.,Ren, X.,Zhou, Y.,Li, G.,Zheng, G.,Huang, N.
Design, synthesis, and bioactivity evaluation of macrocyclic benzo[b]pyrido[4,3-e][1,4]oxazine derivatives as novel Pim-1 kinase inhibitors.
Bioorg.Med.Chem.Lett., 72:128874-128874, 2022

PubMed Abstract: Pim-1 kinase is a serine/threonine kinase which is vital in many tumors. The Pim-1 inhibitor 10-DEBC and its derivatives discovered in our previous work were modified through macrocyclization strategy. A series of benzo[b]pyridine[4,3-e][1,4]oxazine macrocyclic compounds were designed, synthesized, and evaluated as novel Pim-1 kinase inhibitors. Among these compounds, compound H5 exhibited the highest activity with an IC value of 35 nM. In addition, the crystal complex structure of Pim-1 kinase bound with compound H3 was determined, and the structure-activity relationship of these macrocyclic compounds was analyzed, which provides the structural basis of further optimization of novel macrocyclic Pim-1 kinase inhibitors..

PubMed: 35779826
DOI: 10.1016/j.bmcl.2022.128874

Experimental method

X-RAY DIFFRACTION (2.66 Å)