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ChemicalBook--->CAS DataBase List--->2376928-82-2

2376928-82-2

2376928-82-2 Structure

2376928-82-2 Structure
IdentificationBack Directory
[Name]

1H-Pyrazole-4-carboxamide, N-cyclohexyl-3-[[3-fluoro-4-[[6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-quinolinyl]oxy]phenyl]amino]-1-methyl-
[CAS]

2376928-82-2
[Synonyms]

1H-Pyrazole-4-carboxamide, N-cyclohexyl-3-[[3-fluoro-4-[[6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-quinolinyl]oxy]phenyl]amino]-1-methyl-
[Molecular Formula]

C34H41FN6O5
[MOL File]

2376928-82-2.mol
[Molecular Weight]

632.72
Chemical PropertiesBack Directory
[Boiling point ]

795.4±60.0 °C(Predicted)
[density ]

1.33±0.1 g/cm3(Predicted)
[form ]

Solid
[pka]

14.15±0.20(Predicted)
[color ]

Off-white to light yellow
Hazard InformationBack Directory
[Uses]

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-mesenchymal transition (EMT), and inhibits cancer cell migration and invasion[1].
[in vivo]

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].

Animal Model:Xenograft model derived from highly metastatic 4T1 cells.[1]
Dosage:50 or 100 mg/kg
Administration:Oral administration (p.o.)
Result:Suppressed 4T1 tumor growth with a tumor growth inhibition (TGI) of 78.0 and 95.9% at 50 and 100 mg/kg, respectively.
Inhibited the phosphorylation of AXL.
Showed that liver is one of the most common sites of breast cancer metastasis.
Animal Model:Rats[1]
Dosage:5 mg/kg (i.v.), 25 mg/kg (p.o.)
Administration:Intravenous injection (i.v.), oral administration (p.o.)
Result:Pharmacokinetic parameters of AXL-IN-13 (Compound 6li).
parameters T1/2 (h)Cmax (ng/mL)AUClastF (%)
5 mg/kg (i.v.)3.31 12280.4411684.24
25 mg/kg (p.o.)4.22887.75 8410.2114.4
[IC 50]

Axl; PDGFRβ: 2.3 nM (Kd)
[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. DOI:10.1021/acs.jmedchem.2c01346
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