2. Academic Validation
  3. Phosphamide-containing diphenylpyrimidine analogues (PA-DPPYs) as potent focal adhesion kinase (FAK) inhibitors with enhanced activity against pancreatic cancer cell lines

Phosphamide-containing diphenylpyrimidine analogues (PA-DPPYs) as potent focal adhesion kinase (FAK) inhibitors with enhanced activity against pancreatic cancer cell lines

  • Bioorg Med Chem. 2017 Dec 15;25(24):6313-6321. doi: 10.1016/j.bmc.2017.09.041.
He Liu 1,  Bin Wu 1,  Yang Ge 1,  Jiaxin Huang 1,  Shijie Song 1,  Changyuan Wang 1,  Jihong Yao 1,  Kexin Liu 1,  Yanxia Li 2,  Yongming Li 3,  Xiaodong Ma 4
Affiliations

Affiliations

  • 1 College of Pharmacy, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, PR China.
  • 2 Department of Respiratory Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, PR China.
  • 3 College of Pharmacy, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, PR China. Electronic address: liyongming1979@sina.com.
  • 4 College of Pharmacy, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, PR China. Electronic address: xiaodong.ma@139.com.
PMID: 29102081 DOI: 10.1016/j.bmc.2017.09.041
Abstract

A family of phosphamide-containing diphenylpyrimidine analogues (PA-DPPYs) were synthesized as potent focal adhesion kinase (FAK) inhibitors. The PA-DPPY derivatives could significantly inhibit the FAK enzymatic activity at concentrations lower than 10.69 nM. Among them, compounds 7a and 7e were two of the most active FAK inhibitors, possessing IC50 values of 4.25 nM and 4.65 nM, respectively. In particular, compound 7e also displayed strong activity against AsPC cell line, with an IC50 of 1.66 μM, but show low activity against the normal HPDE6-C7 cells (IC50 > 20 μM), indicating its low cell cytotoxicity. Additionally, flow cytometry analysis showed that after treatment with 7e (8 μM, 72 h), both AsPC and Panc cells growth were almost totally inhibited, with a cell viability rate of 16.8% and 18.1%, respectively. Overall, compound 7e may be served as a valuable FAK Inhibitor for the treatment of pancreatic Cancer.

Keywords

FAK; Inhibitor; Pancreatic cancer; Pyrimidine.

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