BenzaMide, N-[4-[(4-ethyl-1-piperazinyl)Methyl]-3-(trifluoroMethyl)phenyl]-4-Methyl-3-[[[5-(2-thienyl)-3-pyridinyl]carbonyl]aMino]-

Biological Activity

alw-ii-41-27 is a potent inhibitor of eph family kinases, with an ic50 value of 11 nm to epha2 [1] [2].eph family proteins are key regulators of both disease and normal development. eph receptors are involved in many intracellular signaling pathways such as pi3k/akt/mtor, ras/raf/mapk, fak, src, abl, and rho/rac/cdc42 [2].in h358 cells, treatment with alw-ii-41-27 at a concentration of 1 μm within 15 minutes impaired the tyrosine phosphorylation of the epha2 receptor and continued to inhibit the tyrosine phosphorylation through 6 hours. alw-ii-41-27 also dose-dependently inhibited the epha2 phosphorylation induced by ligand. when the epha2 was depleted by rnai in nsclc cell lines, cells were much less sensitive to alw-ii-41-27.it was suggested that epha2 plays an oncogenic role according to results in lung cancers. in mice bearing non–small cell lung cancers (nsclcs), intraperitoneal injection with alw-ii-41-27 at a dose of 15 mg/kg twice daily for 14 days significantly resulted in an inhibition of the growth of h358 tumors. alw-ii-41-27 significantly increased the apoptosis of tumors compared with the vehicle alone or ng-25. this was similar to the effect of the genetic ablation of epha2. compared with treatments with vehicle alone or ng-25, treatment with alw-ii-41-27 did not result in significant differences in the vessel density or proliferation of tumors [2].

References

[1]. marialuisa moccia, qingsong liu, teresa guida, et al. identification of novel small molecule inhibitors of oncogenic ret kinase. plos one, 2015, 10(6):e0128364.
[2]. katherine r. amato, shan wang, andrew k. hastings, et al. genetic and pharmacologic inhibition of epha2 promotes apoptosis in nsclc. journal of clinical investigation, 2014, 124(5):2037-2049.