6H3K

Introduction of a methyl group curbs metabolism of pyrido[3,4-d]pyrimidine MPS1 inhibitors and enables the discovery of the Phase 1 clinical candidate BOS172722.

Summary for 6H3K

• Entry DOI: 10.2210/pdb6h3k/pdb
• Descriptor: Dual specificity protein kinase TTK, ~{N}8-(2,2-dimethylpropyl)-~{N}2-[2-ethoxy-4-(4-methyl-1,2,4-triazol-3-yl)phenyl]-6-methyl-pyrido[3,4-d]pyrimidine-2,8-diamine, 2-(2-(2-(2-(2-(2-ETHOXYETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHANOL, ... (4 entities in total)
• Functional Keywords: kinase, spindle assembly checkpoint, mitosis, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 33002.02

Authors

Woodward, H.L.,Hoelder, S. (deposition date: 2018-07-19, release date: 2018-09-19, Last modification date: 2018-10-10)

• Primary citation: Woodward, H.L.,Innocenti, P.,Cheung, K.J.,Hayes, A.,Roberts, J.,Henley, A.T.,Faisal, A.,Mak, G.W.,Box, G.,Westwood, I.M.,Cronin, N.,Carter, M.,Valenti, M.,De Haven Brandon, A.,O'Fee, L.,Saville, H.,Schmitt, J.,Burke, R.,Broccatelli, F.,van Montfort, R.L.M.,Raynaud, F.I.,Eccles, S.A.,Linardopoulos, S.,Blagg, J.,Hoelder, S.; Introduction of a Methyl Group Curbs Metabolism of Pyrido[3,4- d]pyrimidine Monopolar Spindle 1 (MPS1) Inhibitors and Enables the Discovery of the Phase 1 Clinical Candidate N2-(2-Ethoxy-4-(4-methyl-4 H-1,2,4-triazol-3-yl)phenyl)-6-methyl- N8-neopentylpyrido[3,4- d]pyrimidine-2,8-diamine (BOS172722).; J. Med. Chem., 61:8226-8240, 2018; PubMed: 30199249; DOI: 10.1021/acs.jmedchem.8b00690

Experimental method

X-RAY DIFFRACTION (2.48 Å)