| Identification | Back 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 Properties | Back 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 Information | Back 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.
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| 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) | AUClast | F (%) | |
| 5 mg/kg (i.v.) | 3.31 | 12280.44 | 11684.24 | | |
| 25 mg/kg (p.o.) | 4.22 | 887.75 | 8410.21 | 14.4 |
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| [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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