RP1400: A Potent Met Kinase Inhibitor Suppressing Tumor Growth in Cancer Mouse Models

The c-Met proto-oncogene, which encodes the Met protein with tyrosine kinase activity, plays a critical role in cancer development due to its involvement in cell invasion and metastasis. Targeting the Met kinase signaling pathway is a promising therapeutic strategy for Met-driven cancers. RP1400 is a newly developed, selective, and potent Met kinase inhibitor with potential as a clinical candidate.

In the study, the Met kinase activity of RP1400 was evaluated using a specialized assay kit, and its antiproliferative effects were tested on various Met-amplified cancer cell lines. The inhibitor's impact on Met kinase phosphorylation and downstream signaling molecules Akt and Stat-5a was measured in specific cancer cells. The in vivo efficacy of RP1400 was assessed in mouse models of gastric cancer, glioblastoma, and hepatocellular carcinoma, and its pharmacokinetics were studied in Balb/c mice.

Results showed that RP1400 was highly potent against the Met kinase enzyme, with significant selectivity over other kinases. It effectively reduced Met phosphorylation in cancer cells and inhibited the phosphorylation of downstream signaling proteins. RP1400 also displayed strong antiproliferative activity against Met-amplified cell lines with low IC50 values. With a favorable pharmacokinetic profile, RP1400 demonstrated excellent in vivo efficacy, significantly reducing tumor growth in the tested cancer models.

The study concludes that RP1400 is a potent and selective Met kinase inhibitor with strong anti-tumor activity in preclinical models. The compound is currently undergoing toxicological evaluation, with clinical trials expected to be initiated in the first half of 2014.