TL4830031 (compound 8i), a quinolone antibiotic derivatives, is a potent Axl inhibitor with an IC50 value of 26 nM. TL4830031 inhibits the phosphorylation of Axl. TL4830031 inhibits cell invasion and migration. TL4830031 can be used for cancer research[1].
TL4830031 (compound 8i) binds to Axl with a Kd value of 1.1 nM. TL4830031 exhibits a 25 fold less potency against Mer with a Kd value of 25 nM, while it is much less potent to Tyro3 with a Kd value of 750 nM[1].
TL4830031 (0-5000 nM; 4 h; MDA-MB-231 cells) inhibits the phosphorylation of Axl (pAxl (Tyr702)) and the downstream Akt(pAkt(Thr308)) in a dose-dependent manner[1].
TL4830031 (0-5000 nM; 4 h) reverses the expression of the EMT markers induced by TGF-β1 in MDA-MB-231 cells[1].
TL4830031 (0-5000 nM; 24 h) suppresses migration and invasion of MDA-MB-231 cells[1].
Western Blot Analysis[1]
| Cell Line: | MDA-MB-231 cells |
| Concentration: | 0, 8, 40, 200, 1000 and 5000 nM |
| Incubation Time: | 4 hours |
| Result: | Inhibited the phosphorylation of Axl (pAxl (Tyr702)) and the downstream Akt (pAkt(Thr308)) at a low concentration. |
Western Blot Analysis[1]
| Cell Line: | MDA-MB-231 cells |
| Concentration: | 0, 40, 200, 1000 and 5000 nM |
| Incubation Time: | 4 hours |
| Result: | Increased the expression of epithelial marker E-cadherin and decreased the expression of mesenchymal marker N-cadherin in MDA-MB-231 cells. |
TL4830031 (compound 8i) (0-800 mg/kg; p.o.; daily, for 7 d; ICR mice) has toxicity to liver and kidney in ICR mice[1].
TL4830031 (2.5-50 mg/kg; p.o. and i.v.; SD rats) exhibits reasonable pharmacokinetic (PK) properties with an AUC0-∞ value of 25944.7 μg/mL.h and a T1/2 value of 5.68 h at an oral dose of 25 mg/kg. The Cmax (2386.9 µg/L=3.6 µM) occurred at 4.0 h postdose[1].
| Animal Model: | ICR mice[1] |
| Dosage: | 0, 50, 100, 200, 400, 600 and 800 mg/kg |
| Administration: | Oral administration; daily, for 7 days |
| Result: | Had toxicity to liver and kidney at 200 mg/kg, 400 mg/kg and 800 mg/kg administration. |
| Animal Model: | SD rats[1] | |||||||||||||||||||||
| Dosage: | 2.5 and 25 mg/kg | |||||||||||||||||||||
| Administration: | Oral administration (2.5 mg/kg) and intravenous injection (25 mg/kg) | |||||||||||||||||||||
| Result: |
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[1]. Tan L, et, al. Quinolone antibiotic derivatives as new selective Axl kinase inhibitors. Eur J Med Chem. 2019 Mar 15;166:318-327.