Marine sponge polyketide inhibitors of protein tyrosine kinase.
The marine polyketide natural product, halenaquinone, was shown to be an irreversible inhibitor of pp60v-src, the oncogenic protein tyrosine kinase encoded by the Rous sarcoma virus. This compound had an IC50 of approximately 1.5 microM against pp60v-src and also inhibited the ligand-stimulated kinase activity of the human epidermal growth factor receptor with an IC50 of approximately 19 microM. Halenaquinone blocked the proliferation of a number of cultured cell lines, including several transformed by oncogenic protein tyrosine kinases. Halenaquinol, xestoquinone, halenaquinol sulfate, and several simple synthetic quinone analogs were also shown to inhibit pp60v-src.
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Institute of Cancer and Developmental Biology, Syntex Research, Palo Alto, CA 94304.
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Moretti
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D000818:Animals; D001358:Avian Sarcoma Viruses / Q000201:enzymology; D016466:CHO Cells; D002294:Carcinoma, Squamous Cell; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D007700:Kinetics; D015394:Molecular Structure; D015688:Oncogene Protein pp60(v-src) / Q000037:antagonists & inhibitors*; D011161:Porifera; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011809:Quinones / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D011809:Quinones; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src)