2XF0

Crystal structure of checkpoint kinase 1 (Chk1) in complex with inhibitors

Summary for 2XF0

• Entry DOI: 10.2210/pdb2xf0/pdb
• Related: 1IA8 1NVQ 1NVR 1NVS 1ZLT 1ZYS 2AYP 2BR1 2BRB 2BRG 2BRH 2BRM 2BRN 2BRO 2C3J 2C3K 2C3L 2CGU 2CGV 2CGW 2CGX 2WMQ 2WMR 2WMS 2WMT 2WMU 2WMV 2WMW 2WMX 2X8D 2X8E 2X8I 2XEY 2XEZ
• Descriptor: SERINE/THREONINE-PROTEIN KINASE CHK1, 3-PHENYL-6-(1H-PYRAZOL-4-YL)IMIDAZO[1,2-A]PYRAZINE, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: transferase, dna repair, cell cycle
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Nucleus: O14757
• Total number of polymer chains: 1
• Total formula weight: 33552.54

Authors

Matthews, T.P.,McHardy, T.,Klair, S.,Boxall, K.,Fisher, M.,Cherry, M.,Allen, C.E.,Addison, G.J.,Ellard, J.,Aherne, G.W.,Westwood, I.M.,van Montfort, R.,Garrett, M.D.,Reader, J.C.,Collins, I. (deposition date: 2010-05-19, release date: 2010-06-30, Last modification date: 2023-12-20)

Primary citation

Matthews, T.P.,Mchardy, T.,Klair, S.,Boxall, K.,Fisher, M.,Cherry, M.,Allen, C.E.,Addison, G.J.,Ellard, J.,Aherne, G.W.,Westwood, I.M.,Montfort, R.V.,Garrett, M.D.,Reader, J.C.,Collins, I.
Design and Evaluation of 3,6-Di(Hetero)Aryl Imidazo[1,2-A]Pyrazines as Inhibitors of Checkpoint and Other Kinases.
Bioorg.Med.Chem.Lett., 20:4045-, 2010

PubMed Abstract: A range of 3,6-di(hetero)arylimidazo[1,2-a]pyrazine ATP-competitive inhibitors of CHK1 were developed by scaffold hopping from a weakly active screening hit. Efficient synthetic routes for parallel synthesis were developed to prepare analogues with improved potency and ligand efficiency against CHK1. Kinase profiling showed that the imidazo[1,2-a]pyrazines could inhibit other kinases, including CHK2 and ABL, with equivalent or better potency depending on the pendant substitution. These 3,6-di(hetero)aryl imidazo[1,2-a]pyrazines appear to represent a general kinase inhibitor scaffold.

PubMed: 20561787
DOI: 10.1016/J.BMCL.2010.05.096

Experimental method

X-RAY DIFFRACTION (2.4 Å)