An isoquinolinium derivative selectively inhibits MAPK Spc1 of the stress-activated MAPK cascade of Schizosaccharomyces pombe.

Hyun-Jun Kim, Jeong Eun Park, Sangwook Jin, Jung-Ho Kim, Kiwon Song

Department of Biochemistry and Institute of Life Science and Biotechnology, College of Science, Yonsei University, Seoul 120-749, Korea.

Chemistry & biology 2006 Aug

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We have extended the search for selective inhibitors of the kinases of MAPK cascades by screening a derivative library of one of the isoquinoline rings of the protoberberine backbone. HWY 5069 inhibited the proliferation of wild-type and all mutants of Schizosaccharomyces pombe examined, except spc1Delta, at a minimal inhibitory concentration (MIC) of 3.76 microM. HWY 5069 also completely inhibited Spc1 kinase activity in vitro with an IC(50) of 16.4 microM as a competitive inhibitor of substrate binding. It was highly selective for Spc1 and did not affect the activity of other kinases in the MAPK cascades of fission yeast and mammals, including functional homologs of Spc1.

Citation

Hyun-Jun Kim, Jeong Eun Park, Sangwook Jin, Jung-Ho Kim, Kiwon Song. An isoquinolinium derivative selectively inhibits MAPK Spc1 of the stress-activated MAPK cascade of Schizosaccharomyces pombe. Chemistry & biology. 2006 Aug;13(8):881-9