Description
As a novel allosteric, non-ATP-binding inhibitor, TAK-733 can potently and selectively inhibit MEK1/2 with IC50 of 3.2 nM.
Storage
2 years at -20 centigrade
Molecular Formula
C17H15F2IN4O4
Chemical Name
(R)-3-(2,3-dihydroxypropyl)-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione
Solubility
DSMO 101 mg/mL Water
In vitro
As a novel allosteric, non-ATP-binding inhibitor, TAK-733 can potently and selectively inhibit MEK1/2 with IC50 of 3.2 nM. TAK-733 belongs to 5-phenylamino-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione series compound.[1] TAK733 shows strong inhibition to uveal melanoma cell lines with IC50 around 10 nM. Some uveal melanoma cell line is sensitive to TAK733, with IC50 less than 1 nM. TAK733 can induce cell cycle arrest. For both TAK733-sensitive( M207) and TAK733-highly resistant cell line, TAK733,with increasing concentrations, can induce a dose-dependent G1 arrest. TAK733 can induce G1 arrest in melanoma cell lines regardless of their origin, driver oncogenic mutations and in vitro sensitivity to TAK733. TAK733 also can induce a marked dose-dependent decrease of pERK, regardless of the driver oncogenic mutation or the sensitivity or resistance.
In vivo
TAK-733 shows potent inhibition to mouse xenograft models of human cancer, such as melanoma, colorectal, NSCLC, pancreatic and breast cancer.
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