Structural highlights
Publication Abstract from PubMed
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 7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile scaffold. Our lead optimization was guided by key X-ray crystal structure analysis. In vivo evaluation of candidate (9) is shown to effectively mitigate human TNBC cell proliferation.
X-ray Crystal Structure-Guided Design and Optimization of 7H-Pyrrolo[2,3-d]pyrimidine-5-carbonitrile Scaffold as a Potent and Orally Active Monopolar Spindle 1 Inhibitor.,Lee Y, Kim H, Kim H, Cho HY, Jee JG, Seo KA, Son JB, Ko E, Choi HG, Kim ND, Kim I J Med Chem. 2021 May 4. doi: 10.1021/acs.jmedchem.1c00542. PMID:33942608[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lee Y, Kim H, Kim H, Cho HY, Jee JG, Seo KA, Son JB, Ko E, Choi HG, Kim ND, Kim I. X-ray Crystal Structure-Guided Design and Optimization of 7H-Pyrrolo[2,3-d]pyrimidine-5-carbonitrile Scaffold as a Potent and Orally Active Monopolar Spindle 1 Inhibitor. J Med Chem. 2021 May 4. doi: 10.1021/acs.jmedchem.1c00542. PMID:33942608 doi:http://dx.doi.org/10.1021/acs.jmedchem.1c00542
