2. Academic Validation
  3. Discovery of SHR5428 as a selective and noncovalent inhibitor of CDK7

Discovery of SHR5428 as a selective and noncovalent inhibitor of CDK7

  • Bioorg Med Chem Lett. 2023 Sep 1;93:129429. doi: 10.1016/j.bmcl.2023.129429.
Minqiang Jia 1,  Weimin Wang 2,  Gang Chen 2,  Ting Wu 2,  Ting Zhang 2,  Qian Zhou 2,  Junzhao Yin 2,  Jie Li 2,  Xun Li 2,  Yuchang Mao 2,  Jun Feng 2,  Min Hu 2,  Xin Li 2,  Feng He 2
Affiliations

Affiliations

  • 1 R&D Center, Shanghai Hengrui Pharmaceutical Co., Ltd., 279 Wenjing Road, Shanghai 200245, China. Electronic address: [email protected].
  • 2 R&D Center, Shanghai Hengrui Pharmaceutical Co., Ltd., 279 Wenjing Road, Shanghai 200245, China.
PMID: 37543274 DOI: 10.1016/j.bmcl.2023.129429
Abstract

Cyclin dependent kinase 7 (CDK7) is an attractive target in tumor indications via regulating both cell cycle and transcription. Here, SHR5428 was discovered as a selective and noncovalent CDK7 Inhibitor with highly potent CDK7 enzymatic activity and triple negative breast Cancer cellular activity on MDA-MB-468 cell. SHR5428 also displayed favorable pharmacokinetic properties in different preclinical species such as mouse, rat and dog, and showed high selectivity over CDK1, CDK2, CDK4, CDK6, CDK9, CDK12 in CDK family. Furthermore, the computational modeling has shed some LIGHT on this mechanism. Additionally the in vivo efficacy study in a breast Cancer cell line (HCC70 cell) derived xenograft mouse model proved SHR5428 to be orally efficacious with dose-dependent tumor growth inhibition.

Keywords

CDK7; Efficacy; SAR; Triple negative breast cancer.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-155787
    CDK7 Inhibitor
    CDK