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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Beta-hydroxyisovalerylshikonin is a novel and potent inhibitor of protein tyrosine kinases.

Beta-hydroxyisovalerylshikonin (beta-HIVS), a compound isolated from Lithospermium radix, most efficiently induced cell-death in two lines of lung cancer cells, namely, NCI-H522 and DMS114, whereas shikonin was effective against a wide variety of tumor cell lines. During our studies of the mechanism of action of beta-HIVS on tumor cells, we found that this compound inhibited protein tyrosine kinase (PTK) activity. The tyrosine kinase activities of a receptor for EGF (EGFR) and v-Src were strongly inhibited and that of KDR/Flk-1 was weakly inhibited by beta-HIVS. The inhibition by beta-HIVS of the activities of EGFR and v-Src was much stronger than that by shikonin. The IC50 values of beta-HIVS for EGFR and v-Src were approximately 0.7 microM and 1 microM, respectively. Moreover, the inhibition of v-Src by beta-HIVS was non-competitive with respect to ATP. These results strongly suggest that the action of beta-HIVS, as well as that of shikonin, involves the inhibition of PTK, and they also suggest the possibility of producing a novel group of PTK inhibitors based on shikonin as the parent compound.[1]


  1. Beta-hydroxyisovalerylshikonin is a novel and potent inhibitor of protein tyrosine kinases. Hashimoto, S., Xu, Y., Masuda, Y., Aiuchi, T., Nakajo, S., Uehara, Y., Shibuya, M., Yamori, T., Nakaya, K. Jpn. J. Cancer Res. (2002) [Pubmed]
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