2. Academic Validation
  3. 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

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. 2021 May 27;64(10):6985-6995. doi: 10.1021/acs.jmedchem.1c00542.
Younho Lee 1 2,  Hyunkyung Kim 2 3,  Haelee Kim 4,  Ha Yeon Cho 4,  Jun-Goo Jee 3,  Kyung-Ah Seo 2,  Jung Beom Son 2,  Eunhwa Ko 4,  Hwan Geun Choi 4,  Nam Doo Kim 2,  Ikyon Kim 1
Affiliations

Affiliations

  • 1 College of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, South Korea.
  • 2 Voronoibio, S11 Floor, 32 Songdogwahak-ro, Yeonsu-gu, Incheon 21984, South Korea.
  • 3 Research Institute of Pharmaceutical Researches, College of Pharmacy, Kyungpook National University, Daegu 41566, Republic of Korea.
  • 4 B2Sbio, S23 Floor, 32 Songdogwahak-ro, Yeonsu-gu, Incheon 21984, South Korea.
PMID: 33942608 DOI: 10.1021/acs.jmedchem.1c00542
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 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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-165421
    Mps1抑制剂
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