| Identification | Back Directory | [Name]
2-Pyridinemethanol, 4-[[4-[[1-cyclopropyl-3-(3,3-difluorocyclobutyl)-1H-pyrazol-4-yl]oxy]-2-pyridinyl]amino]-α,α-dimethyl- | [CAS]
2421135-03-5 | [Synonyms]
TGFβRI-IN-4
2-Pyridinemethanol, 4-[[4-[[1-cyclopropyl-3-(3,3-difluorocyclobutyl)-1H-pyrazol-4-yl]oxy]-2-pyridinyl]amino]-α,α-dimethyl- | [Molecular Formula]
C23H25F2N5O2 | [MOL File]
2421135-03-5.mol | [Molecular Weight]
441.48 |
| Hazard Information | Back Directory | [Uses]
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]. | [in vivo]
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. |
| [References]
[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. DOI:10.1016/j.ejmech.2020.112354 |
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