Fragment-Based Drug Discovery of Potent Protein Kinase C Iota Inhibitors

  • J Med Chem. 2018 May 24;61(10):4386-4396. doi: 10.1021/acs.jmedchem.8b00060.
Jacek Kwiatkowski  1 ,  Boping Liu  1 ,  Doris Hui Ying Tee  1 ,  Guoying Chen  1 ,  Nur Huda Binte Ahmad  1 ,  Yun Xuan Wong  1 ,  Zhi Ying Poh  1 ,  Shi Hua Ang  1 ,  Eldwin Sum Wai Tan  1 ,  Esther Hq Ong  1 ,  Nurul Dinie  1 ,  Anders Poulsen  1 ,  Vishal Pendharkar  1 ,  Kanda Sangthongpitag  1 ,  May Ann Lee  1 ,  Sugunavathi Sepramaniam  1 ,  Soo Yei Ho  1 ,  Joseph Cherian  1 ,  Jeffrey Hill  1 ,  Thomas H Keller  1 ,  Alvin W Hung  1
Affiliations
  • 1. Experimental Therapeutics Centre , Agency for Science, Technology and Research (A*STAR) , 11 Biopolis Way, Helios #03-10/11 , Singapore 138667 , Singapore.
PMID: 29688013 DOI: 10.1021/acs.jmedchem.8b00060
Abstract

Protein kinase C iota (PKC-ι) is an atypical kinase implicated in the promotion of different Cancer types. A biochemical screen of a fragment library has identified several hits from which an azaindole-based scaffold was chosen for optimization. Driven by a structure-activity relationship and supported by molecular modeling, a weakly bound fragment was systematically grown into a potent and selective inhibitor against PKC-ι.

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