7CLH

Crystal structure of TTK kinase domain in complex with compound 19

Summary for 7CLH

• Entry DOI: 10.2210/pdb7clh/pdb
• Descriptor: Dual specificity protein kinase TTK, 2-[[2-methoxy-4-(2-oxidanylidenepyrrolidin-1-yl)phenyl]amino]-4-(methylamino)-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile (3 entities in total)
• Functional Keywords: kinase mps1 ttk structure-guided drug design, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 33398.89

Authors

Kim, H.L.,Cho, H.Y.,Park, Y.W.,Lee, Y.H.,Son, J.B.,Ko, E.H.,Choi, H.G.,Kim, N.D. (deposition date: 2020-07-21, release date: 2021-05-12, Last modification date: 2024-10-23)

Primary citation

Lee, Y.,Kim, H.,Kim, H.,Cho, H.Y.,Jee, J.G.,Seo, K.A.,Son, J.B.,Ko, E.,Choi, H.G.,Kim, N.D.,Kim, I.
X-ray Crystal Structure-Guided Design and Optimization of 7 H -Pyrrolo[2,3- d ]pyrimidine-5-carbonitrile Scaffold as a Potent and Orally Active Monopolar Spindle 1 Inhibitor.
J.Med.Chem., 64:6985-6995, 2021

PubMed Abstract: Triple-negative breast cancer (TNBC) is an aggressive breast-cancer subtype associated with poor prognosis and high relapse rates. Monopolar spindle 1 kinase (MPS1) is an apical dual-specificity protein kinase that is over-expressed in TNBC. We herein report a highly selective MPS1 inhibitor based on a 7-pyrrolo[2,3-]pyrimidine-5-carbonitrile scaffold. Our lead optimization was guided by key X-ray crystal structure analysis. evaluation of candidate () is shown to effectively mitigate human TNBC cell proliferation.

PubMed: 33942608
DOI: 10.1021/acs.jmedchem.1c00542

Experimental method

X-RAY DIFFRACTION (2.9 Å)