2ywp
From Proteopedia
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| , resolution 2.90Å | |||||||
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| Ligands: | |||||||
| Gene: | CHEK1, CHK1 (Homo sapiens) | ||||||
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 | ||||||
| Related: | 2AYP
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of CHK1 with a Urea Inhibitor
Overview
Based on the X-ray crystallography of our lead compound 1-(5-chloro-2,4-dimethoxyphenyl)-3-(5-cyanopyrazin-2-yl)urea in the checkpoint kinase 1 (Chk1) enzyme, we modified R4, and to a lesser extent, R2, and R5 of the phenyl ring, and made a variety of N-aryl-N'-pyrazinylurea Chk1 inhibitors. Enzymatic activity less than 20 nM was observed in 15 of 41 compounds. Compound 8i provided the best overall results in the cellular assays as it abrogated doxorubicin-induced cell cycle arrest (IC50=1.7 microM) and enhanced doxorubicin cytotoxicity (IC50=0.44 microM) while displaying no single agent activity.
About this Structure
2YWP is a Single protein structure of sequence from Homo sapiens. This structure supersedes the now removed PDB entry 2FGA. Full crystallographic information is available from OCA.
Reference
Synthesis and biological evaluation of 1-(2,4,5-trisubstituted phenyl)-3-(5-cyanopyrazin-2-yl)ureas as potent Chk1 kinase inhibitors., Li G, Hasvold LA, Tao ZF, Wang GT, Gwaltney SL 2nd, Patel J, Kovar P, Credo RB, Chen Z, Zhang H, Park C, Sham HL, Sowin T, Rosenberg SH, Lin NH, Bioorg Med Chem Lett. 2006 Apr 15;16(8):2293-8. Epub 2006 Jan 30. PMID:16446090
Page seeded by OCA on Mon Mar 31 05:16:06 2008
