2. Academic Validation
  3. Discovery of Potent, Selective, and Orally Bioavailable DYRK2 Inhibitors for the Treatment of Prostate Cancer

Discovery of Potent, Selective, and Orally Bioavailable DYRK2 Inhibitors for the Treatment of Prostate Cancer

  • J Med Chem. 2023 Dec 14;66(23):16235-16256. doi: 10.1021/acs.jmedchem.3c01626.
Kai Yuan 1 2,  Fei Xia 1 2,  Qiannan Li 1 3,  Mingming Zheng 1 2,  Hongtao Shen 1 3,  Weijiao Chen 1 2,  Huanaoyu Yang 1 2,  Xujie Zhuang 1 2,  Xiao-Yu Zhang 1 2,  Yibei Xiao 1 3 4,  Peng Yang 1 2 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
  • 2 Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
  • 3 Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
  • 4 Institute of Innovative Drug Discovery and Development, China Pharmaceutical University, Nanjing 211198, China.
PMID: 38033250 DOI: 10.1021/acs.jmedchem.3c01626
Abstract

Prostate Cancer (PCa) seriously threatens male health, and targeting dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) has been verified to reduce PCa burden, while the research progress on the DYRK2 inhibitors was relatively slow. In this work, we discovered DYRK2 Inhibitor 12 (IC50 = 9681 nM) through virtual screening. Subsequently, we performed systematic structural optimization to obtain 54 (IC50 = 14 nM). Compound 54 exhibited high selectivity among 215 kinases and significantly suppressed the proliferation and metastasis of PCa cells in vitro. Moreover, compound 54 displayed high safety, favorable bioavailability, and potent tumor growth inhibitory activity in vivo, which could be used as a potential candidate in the discovery of novel anti-PCa drugs.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-161014
    DYRK2 Inhibitor