nt157 is an irs-1/2 inhibitor.insulin receptor substrates 1 and 2 (irs1/2) mediate antiapoptotic and mitogenic signaling from insulin receptor (ir), insulin-like growth factor 1 receptor (igf-ir), and other oncoproteins. irs1 plays a critical role in cancer cell proliferation, and its expression is increased in many human malignancies.
nt157 treatment was fonund to be able to lead to dose-dependent suppression of irs protein expression, inhibition of igf1r activation, inhibition of igf1-induced akt activation, but increased erk activation in nt157-treated cells. these effects were associated with decreased proliferation, increased apoptosis of lncap cells and increased g2-m arrest in pc3 cells. moreover, nt157 could significantly affect the cell migratory ability, as demonstrated by a wound-healing assay. in addition, the nt157 treatment was able to induce cell cycle arrest and inhibit igf system signaling [1].
in previous animal study, nt157 was found to suppress androgen-responsive growth, delay crpc progression of lncap xenografts, and suppress pc3 tumor growth alone or in combination with docetaxel. this study reported the first preclinical proof-of-principle data that nt157 suppressed irs1/2 expression, delayed crpc progression, and suppressed growth of crpc tumors in vivo [1].
[1] ibuki n et al. the tyrphostin nt157 suppresses insulin receptor substrates and augments therapeutic response of prostate cancer. mol cancer ther. 2014 dec;13(12):2827-39.
