APS6-45 is an orally active tumor-calibrated inhibitor (TCI). APS6-45 inhibits RAS/MAPK signaling and exhibits antitumor activity[1].
APS6-45 (3-30 nM; 3 weeks) strongly suppresses TT human Medullary Thyroid Carcinoma (MTC) cells colony formation in a soft agar assay[1].APS6-45 (1 μM; 1 h) strongly inhibits RAS pathway activity signaling in human MTC cell lines TT and MZ-CRC-1[1].
APS6-45 (10 mg/kg; p.o. daily for 30 d) inhibits growth of TT tumors in mice and does not affect body weight[1].APS6-45 (0.1-160 mg/kg; a single p.o.) does not cause detectable toxic effects in mice[1].APS6-45 (20 mg/kg; a single p.o.) exhibits long half-life (5.6 h), Cmax (9.7 µM) and AUC0-24 (123.7 µM•h) in mice[1]. Animal Model: Female nude mice (6 weeks) are implanted with TT cells[1]
[1]. Sonoshita M, et, al. A whole-animal platform to advance a clinical kinase inhibitor into new disease space. Nat Chem Biol. 2018 Mar;14(3):291-298.