TGFβRI-IN-4

TGFβRI-IN-4 is a highly potent and orally active TGFβ receptor type I (TGFβRI) inhibitor, with IC50s of 44 nM and 42.5 nM for ALK5 and NIH3T3. TGFβRI-IN-4 can suppress tumor growth and tumor weight in tumor xenograft model[1].

Research Areas >> Cancer

IC50: 44 nM (ALK5), 42.5 nM (NIH3T3)[1]

TGFβRI-IN-4 (compound 15r) (60 mg/kg; PO; BID, for 21 days) efficiently suppresses tumor growth and tumor weight in tumor xenograft model[1]. TGFβRI-IN-4 (1 mg/kg and 10 mg/kg; IV and PO; single) exhibits good oral plasma exposure and excellent bioavailability[1]. Pharmacokinetic Parameters of TGFβRI-IN-4 in male Sprague-Dawley rats[1]. IV (1 mg/kg) PO (10 mg/kg) T1/2 (h) 0.5 1.8 CL (L/h/kg) 4.9 Cmax (ng/mL) 926.0 VSS (L/kg) 3.0 AUC0-24 (ng/mL·h) 195.2 2351.2 F (%) 120.5% Animal Model: Female BALB/C mice (5-8 weeks; injected with CT26 cells)[1] Dosage: 60 mg/kg Administration: PO; BID, for 21 days Result: Efficiently suppressed tumor growth (tumor growth inhibition = 65.7%) and tumor weight. Animal Model: Male BALB/C mice[1] Dosage: 1 mg/kg and 10 mg/kg Administration: IV and PO; single (Pharmacokinetic Analysis) Result: Exhibited good oral plasma exposure and excellent bioavailability with AUC >2000 h·ng/mL and F > 80%, respectively.

[1]. Xu G, et al. Synthesis and biological evaluation of 4-(pyridin-4-oxy)-3-(3,3-difluorocyclobutyl)-pyrazole derivatives as novel potent transforming growth factor-β type 1 receptor inhibitors. Eur J Med Chem. 2020;198:112354.