3F9N

Crystal structure of chk1 kinase in complex with inhibitor 38

Summary for 3F9N

• Entry DOI: 10.2210/pdb3f9n/pdb
• Descriptor: Serine/threonine-protein kinase Chk1, 3-(3-chlorophenyl)-2-({(1S)-1-[(6S)-2,8-diazaspiro[5.5]undec-2-ylcarbonyl]pentyl}sulfanyl)quinazolin-4(3H)-one, SULFATE ION, ... (4 entities in total)
• Functional Keywords: chek1, chk1, kinase, cell cycle checkpoint, atp-binding, cytoplasm, dna damage, dna repair, nucleotide-binding, nucleus, phosphoprotein, polymorphism, serine/threonine-protein kinase, transferase, ubl conjugation
• Biological source: Homo sapiens
• Cellular location: Nucleus: O14757
• Total number of polymer chains: 1
• Total formula weight: 37522.21

Authors

Yan, Y.,Munshi, S.,Ikuta, M. (deposition date: 2008-11-14, release date: 2009-01-20, Last modification date: 2023-09-06)

Primary citation

Converso, A.,Hartingh, T.,Garbaccio, R.M.,Tasber, E.,Rickert, K.,Fraley, M.E.,Yan, Y.,Kreatsoulas, C.,Stirdivant, S.,Drakas, B.,Walsh, E.S.,Hamilton, K.,Buser, C.A.,Mao, X.,Abrams, M.T.,Beck, S.C.,Tao, W.,Lobell, R.,Sepp-Lorenzino, L.,Zugay-Murphy, J.,Sardana, V.,Munshi, S.K.,Jezequel-Sur, S.M.,Zuck, P.D.,Hartman, G.D.
Development of thioquinazolinones, allosteric Chk1 kinase inhibitors.
Bioorg.Med.Chem.Lett., 19:1240-1244, 2009

PubMed Abstract: A high throughput screening campaign was designed to identify allosteric inhibitors of Chk1 kinase by testing compounds at high concentration. Activity was then observed at K(m) for ATP and at near-physiological concentrations of ATP. This strategy led to the discovery of a non-ATP competitive thioquinazolinone series which was optimized for potency and stability. An X-ray crystal structure for the complex of our best inhibitor bound to Chk1 was solved, indicating that it binds to an allosteric site approximately 13A from the ATP binding site. Preliminary data is presented for several of these compounds.

PubMed: 19155174
DOI: 10.1016/j.bmcl.2008.12.076

Experimental method

X-RAY DIFFRACTION (1.9 Å)