AXL-IN-13 is a potent and orally active AXL inhibitor (IC50: 1.6 nM, Kd: 0.26 nM). AXL-IN-13 reverses TGF-β1-induced epithelial-mesencmal transition (EMT), and inhibits cancer cell migration and invasion.
AXL-IN-13 (compound 6li) inhibits Ba/F3-TEL-AXL cell proliferation with an IC50 of 4.7 nM (determined by ELISA)[1].AXL-IN-13 also shopws binding affinities against CSF1R, FLT1/3/4, KLT, PDGFRB, TIE2[1].AXL-IN-13 (0-500 nM, 6 h) inhibits the phosphorylation of AXL in MDA-MB-231 and 4T1 cells[1].AXL-IN-13 (0-3 μM, 3 days) blocks EMT induced by TGF-β1 (10 ng/mL) in MDA-MB-231 cells[1].AXL-IN-13 (0-3 μM, 24 h) suppresses MDA-MB-231 cell migration and invasion induced by TGF-β1 (10 ng/mL)[1].
AXL-IN-13 (compound 6li) (50 or 100 mg/kg, p.o, 14 days) inhibits 4T1 tumor growth and metastasis[1].AXL-IN-13 (25 mg/kg, p.o.) displays reasonable PK profiles with an AUC of 8410.21 ng/mL•h, a T1/2 value of 4.22 h, and an oral bioavailability (F) of 14.4%[1].
References:
[1]. Chan S, et al. Discovery of 3-Aminopyrazole Derivatives as New Potent and Orally Bioavailable AXL Inhibitors. J Med Chem. 2022 Nov 24;65(22):15374-15390.