| Description |
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].
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| Related Catalog |
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| In Vitro |
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.
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| In Vivo |
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: 1.19 Administration p.o. (25 mg/kg) i.v. (2.5 mg/kg) AUC0-∞ (μg/mL·h) 25944.7 20680.6 Cmax (ng/mL) 2386.9 4358.2 T1/2 (h) 5.68 4.26 Tmax (h) 4.0 CLz (L/h/kg) 0.12 BA (%) 12.5
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| References |
[1]. Tan L, et, al. Quinolone antibiotic derivatives as new selective Axl kinase inhibitors. Eur J Med Chem. 2019 Mar 15;166:318-327.
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