Biological Activity
tak-285 is a potent inhibitor of her2 and egfr with ic50 value of 17 nm and 23 nm, respectively [1].egfr (epidermal growth factor receptor) and her2 are members of erbb family of receptors and play an important role in stimulating its intrinsic intracellular protein-tyrosine kinase activity. it has been shown that the over-expressions of her-2 and egfr are correlated with a variety of cancers and thus be regarded as promising target in clinic [2].tak-285 is a selective her2 and egfr inhibitor and has a different selectivity with the reported her inhibitor ast-6. when tested with a panel of breast cancer cell lines, cells over-expressed her2 (bt-474, nci-n87, sk-br-3, calu-3, and mda-mb-453) or egfr (a-431) were more sensitive to tak-285 treatment while normal expressed cell line (mrc-5) was less sensitive [1]. [3].in rat model with 4-1st (over-express her2) or a-431 (over-express egfr) subcutaneous xenograft, administration of tak-285 caused significant reduction of tumor growth with t/c values of 14% and 13%, respectively, at a dose of 12.5 mg/kg, compared with control group [1]. in a panel of human breast cancer cell lines expressing egfr, her2, her3, and her4, administration of tak-285 significantly inhibited cell proliferation in a dose-dependent manner with ic50 values range from 0.011 to 17 μm [3].it is also reported that tak-285 inhibited akt and mapk phosphorylation with ic50 value of 0.015 μm and <0.0063 μm, respectively [1].
References
[1]. nakayama, a., et al., antitumor activity of tak-285, an investigational, non-pgp substrate her2/egfr kinase inhibitor, in cultured tumor cells, mouse and rat xenograft tumors, and in an her2-positive brain metastasis model. j cancer, 2013. 4(7): p. 557-65.
[2]. lyakhov, i., et al., her2- and egfr-specific affiprobes: novel recombinant optical probes for cell imaging. chembiochem, 2010. 11(3): p. 345-50.
[3]. takagi, s., et al., her2 and her3 cooperatively regulate cancer cell growth and determine sensitivity to the novel investigational egfr/her2 kinase inhibitor tak-285. oncoscience, 2014. 1(3): p. 196-204.
