INCB28060抑制剂、激动剂(CAS号1029712-80-8)INCB28060是高活性c-MET口服活性抑制剂,IC50为0.13 nM。 Description:
IC50 Value: 0.13±0.05 nM( for recombinant human wild-type c-MET) [1]
INCB28060 is a novel orally active inhibitor (IC50: 0.13nM) of c-MET kinase. INCB28060 potently and specifically inhibits c-MET enzyme activity, c-MET-mediated signal transduction, and the c-MET-dependent neoplastic phenotype of tumor cells .
in vitro: INCB28060 exhibits picomolar enzymatic potency and is highly specific for c-MET with more than 10,000-fold selectivity over a large panel of human kinases. This inhibitor potently blocks c-MET phosphorylation and activation of its key downstream effectors in c-MET-dependent tumor cell lines [1].
in vivo: Oral dosing of INCB28060 results in time- and dose-dependent inhibition of c-MET phosphorylation and tumor growth in c-MET-driven mouse tumor models, and the inhibitor is well tolerated at doses that achieve complete tumor inhibition [1]. Activated c-MET positively regulates the activity of epidermal growth factor receptors (EGFR) and HER-3, as well as expression of their ligands. These effects are reversed with INCB28060 treatment.
Toxicity: INCB28060 was well tolerated at all doses during the treatment periods, with no evidence of overt toxicity or weight loss [1].
Clinical trial: INC-280 and Erlotinib Hydrochloride in Treating Patients With Non-small Cell Lung Cancer. Phase 1