Thiazolidine-diones. Biochemical and biological activity of a novel class of tyrosine protein kinase inhibitors

Various derivatives of thiazolidine-diones have been identified as tyrosine protein kinase inhibitors. The epidermal growth factor (EGF) receptor kinase and c-src kinase were inhibited in vitro with IC50 values in the range of 1-7 microM. The v-abl tyrosine protein kinase was not inhibited by thiazo...

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Veröffentlicht in:The Journal of biological chemistry 1990-12, Vol.265 (36), p.22255-22261
Hauptverfasser: Geissler, J F, Traxler, P, Regenass, U, Murray, B J, Roesel, J L, Meyer, T, McGlynn, E, Storni, A, Lydon, N B
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Sprache:eng
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Zusammenfassung:Various derivatives of thiazolidine-diones have been identified as tyrosine protein kinase inhibitors. The epidermal growth factor (EGF) receptor kinase and c-src kinase were inhibited in vitro with IC50 values in the range of 1-7 microM. The v-abl tyrosine protein kinase was not inhibited by thiazolidine-diones. Inhibition was found to be specific for tyrosine protein kinases. Inhibition of serine/threonine protein kinases was not observed. The active derivatives were shown to inhibit EGF-induced receptor autophosphorylation, either in vitro or in intact cells, and were also found to inhibit growth of the EGF-dependent BALB/MK and A431 cell lines (IC50 1-3 microM). Growth of the interleukin-3-dependent myeloid cell line FDC-P1 was inhibited with equal efficiency. Thus, in these cell lines, members of the c-src kinase family are also potential targets for inhibition by the compounds.
ISSN:0021-9258
1083-351X
DOI:10.1016/S0021-9258(18)45697-9