5F4N

Multi-parameter lead optimization to give an oral CHK1 inhibitor clinical candidate: (R)-5-((4-((morpholin-2-ylmethyl)amino)-5-(trifluoromethyl)pyridin-2-yl)amino)pyrazine-2-carbonitrile (CCT245737)

Summary for 5F4N

• Entry DOI: 10.2210/pdb5f4n/pdb
• Descriptor: Serine/threonine-protein kinase Chk1, methyl 6-[(5-cyanopyrazin-2-yl)amino]-4-[[(2~{R})-morpholin-2-yl]methylamino]pyridine-3-carboxylate, 1,2-ETHANEDIOL, ... (5 entities in total)
• Functional Keywords: inhibitor dna-damage chk1-potency herg-activity, transferase
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus: O14757
• Total number of polymer chains: 1
• Total formula weight: 32628.46

Authors

Collins, I.,Garrett, M.D.,van Montfort, R.,Osborne, J.D.,Matthews, T.P.,McHardy, T.,Proisy, N.,Cheung, K.J.,Lainchbury, M.,Brown, N.,Walton, M.I.,Eve, P.D.,Boxall, K.J.,Hayes, A.,Henley, A.T.,Valenti, M.R.,De Haven Brandon, A.K.,Box, G.,Westwood, I.M.,Jamin, Y.,Robinson, S.P.,Leonard, P.,Reader, J.C.,Aherne, G.W.,Raynaud, F.I.,Eccles, S.A. (deposition date: 2015-12-03, release date: 2016-05-25, Last modification date: 2016-06-22)

• Primary citation: Osborne, J.D.,Matthews, T.P.,McHardy, T.,Proisy, N.,Cheung, K.M.,Lainchbury, M.,Brown, N.,Walton, M.I.,Eve, P.D.,Boxall, K.J.,Hayes, A.,Henley, A.T.,Valenti, M.R.,De Haven Brandon, A.K.,Box, G.,Jamin, Y.,Robinson, S.P.,Westwood, I.M.,van Montfort, R.L.,Leonard, P.M.,Lamers, M.B.,Reader, J.C.,Aherne, G.W.,Raynaud, F.I.,Eccles, S.A.,Garrett, M.D.,Collins, I.; Multiparameter Lead Optimization to Give an Oral Checkpoint Kinase 1 (CHK1) Inhibitor Clinical Candidate: (R)-5-((4-((Morpholin-2-ylmethyl)amino)-5-(trifluoromethyl)pyridin-2-yl)amino)pyrazine-2-carbonitrile (CCT245737).; J.Med.Chem., 59:5221-5237, 2016; PubMed: 27167172; DOI: 10.1021/acs.jmedchem.5b01938

Experimental method

X-RAY DIFFRACTION (1.91 Å)