2. Academic Validation
  3. Design, synthesis and biological evaluation of AKT inhibitors bearing a piperidin-4-yl appendant

Design, synthesis and biological evaluation of AKT inhibitors bearing a piperidin-4-yl appendant

  • Medchemcomm. 2018 Jul 3;9(8):1340-1350. doi: 10.1039/c8md00197a.
Daoguang Zhang 1,  Dongdong Tong 2,  Dezhi Yang 3,  Jing Sun 4,  Fenghe Zhang 2,  Guisen Zhao 1
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry , Key Laboratory of Chemical Biology (Ministry of Education) , School of Pharmaceutical Sciences , Shandong University , Jinan , Shandong 250012 , PR China . Email: guisenzhao@sdu.edu.cn ; ; Tel: +86 531 88382009.
  • 2 Department of Oral and Maxillofacial Surgery , School of Stomatology , Shandong Provincial Key Laboratory of Oral Tissue Regeneration , Shandong University , Jinan , Shandong 250012 , PR China . Email: zfengh@sdu.edu.cn ; ; Tel: +86 531 88382961.
  • 3 National Pharmaceutical Experimental Teaching Demonstration Center, School of Pharmacy , Zunyi Medical University , Zunyi , Guizhou 563003 , PR China.
  • 4 Department of Bone Metabolism , School of Stomatology, Shandong Provincial Key Laboratory of Oral Tissue Regeneration , Shandong University , Jinan , Shandong 250012 , PR China.
PMID: 30151089 DOI: 10.1039/c8md00197a
Abstract

A series of Akt inhibitors possessing a piperidin-4-yl side chain was designed and synthesized. Some of them showed high Akt1 inhibitory activity and potent anti-proliferative effect on PC-3 prostate Cancer cells in the preliminary screening. Further studies revealed the most potent compound, 10h, as a pan-AKT inhibitor. Compound 10h was able to inhibit the cellular phosphorylation of Akt effectively and induce Apoptosis of PC-3 cells. It also showed high metabolic stability in human liver microsomes. Preclinical characterization of 10h, a promising lead Akt Inhibitor, as a potential anti-prostate Cancer therapeutic needs to be further investigated.

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