Savolitinib is a potent, selective, and orally bioavailable c-Met inhibitor with IC50s of 5nM and 3nM for c-Met and p-Met, respectively[1,2]. Savolitinib is commonly used in cancer research.
In vitro, Savolitinib displayed anti‐proliferative activity against SNU‐5, SNU‐638, Hs746T, SNU‐620, GTL16 and IM95m (EC50 values of 0.6, 0.8, 1.3, 3.5, 5.6 and 14.7nM, respectively) which harbor aberrant cMet signaling[2].
In vivo, Savolitinib (0.25-30mg/kg/day; oral; 28 days) treatment led to marked decreases in tumor growth of H1993 and EBC-1 tumor xenografts[3]. Savolitinib (1, 10mg/kg/day; oral; 14–21 days) significantly reduced tumor weight in all 3 cMET‐amplified gastric cancer PDX models[2]. Savolitinib (1, 2.5 and 10.0mg/kg; oral; 21 days) dose-dependently reduced tumor growth in U87MG subcutaneous xenograft model[1]. Savolitinib (15mg/kg; oral; 15 days) reduced tumor growth, resulting in approximately 84% tumor growth inhibition (TGI) in the EGFRm MET-amplified NSCLC PDX model[4].
References:
[1]. Jia, Hong, et al. "Discovery of (S)-1-(1-(Imidazo [1, 2-a] pyridin-6-yl) ethyl)-6-(1-methyl-1 H-pyrazol-4-yl)-1 H-[1, 2, 3] triazolo [4, 5-b] pyrazine (Volitinib) as a Highly Potent and Selective Mesenchymal–Epithelial Transition Factor (c-Met) Inhibitor in Clinical Development for Treatment of Cancer." Journal of medicinal chemistry 57.18 (2014): 7577-7589.
[2]. Gavine, Paul R., et al. "Volitinib, a potent and highly selective c-Met inhibitor, effectively blocks c-Met signaling and growth in c-MET amplified gastric cancer patient-derived tumor xenograft models." Molecular oncology 9.1 (2015): 323-333.
[3]. Henry, Ryan E., et al. "Acquired savolitinib resistance in non-small cell lung cancer arises via multiple mechanisms that converge on MET-independent mTOR and MYC activation." Oncotarget 7.36 (2016): 57651.
[4]. Jones, Rhys DO, et al. "Pharmacokinetic/pharmacodynamic analysis of savolitinib plus osimertinib in an EGFR mutation–positive, MET-amplified non–small cell lung cancer model." Molecular Cancer Therapeutics 22.5 (2023): 679-690.