1. Academic Validation
  2. Discovery, Optimization, and Evaluation of Selective CDK4/6 Inhibitors for the Treatment of Breast Cancer

Discovery, Optimization, and Evaluation of Selective CDK4/6 Inhibitors for the Treatment of Breast Cancer

  • J Med Chem. 2022 Nov 24;65(22):15102-15122. doi: 10.1021/acs.jmedchem.2c00947.
Weijiao Chen 1 Minghui Ji 1 Hao Cheng 1 2 Mingming Zheng 1 Fei Xia 1 Wenjian Min 1 Huanaoyu Yang 1 Xiao Wang 1 Liping Wang 1 Lijuan Cao 2 Kai Yuan 1 Peng Yang 1 3
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
  • 2 State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism, China Pharmaceutical University, Nanjing 210009, China.
  • 3 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Abstract

Breast Cancer is the most common tumor in women, and selective cyclin-dependent kinase (CDK) 4/6 inhibitors played an important role in the treatment of breast Cancer. Therefore, discovering selective CDK4/6 inhibitors with great safety and potent efficacy is beneficial for the breast Cancer treatment. In our work, the lead compound 8 was identified through virtual screening; then, systematic structural optimization was conducted to afford 42, which exhibited strong inhibition on CDK4/6 and showed high selectivity among 205 kinases. 42 possessed excellent safety profiles (LD50 > 5,000 mg/kg), favorable pharmacokinetic properties (F % = 43%), and potent efficacy in reducing the burden of breast Cancer in vivo. In conclusion, we offered a highly selective CDK4/6 inhibitor, which could be used as a great candidate for further preclinical studies of breast Cancer.

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Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-151898
    CDK4/6 Inhibitor
    CDK