AXL-IN-13 是一种有效的、具有口服活性的AXL抑制剂 (IC50: 1.6 nM，Kd: 0.26 nM)。AXL-IN-13 逆转 TGF-β1 诱导的上皮间质转化 (EMT)，并抑制癌细胞迁移和侵袭。
| 生物活性 | AXL-IN-13 is a potent and orally activeAXLinhibitor (IC50: 1.6 nM,Kd: 0.26 nM). AXL-IN-13 reverses TGF-β1-induced epithelial-mesenchymal transition (EMT), and inhibitscancercell migration and invasion[1]. |
| IC50& Target[1] | |
体外研究
(In Vitro) | AXL-IN-13 (化合物 6li) 抑制 Ba/F3-TEL-AXL 细胞增殖，IC50为 4.7 nM (通过 ELISA 测定)[1].
AXL-IN-13 还显示对 CSF1R、FLT1/3/4、KLT、PDGFRB、TIE2 的结合亲和力[1]。
AXL-IN-13 (0-500 nM，6 小时) 抑制 MDA-MB-231 和 4T1 细胞中 AXL 的磷酸化[1]。
AXL-IN-13 (0-3 μM，3 天) 阻断 MDA-MB-231 细胞中 TGF-β1 (10 ng/mL) 诱导的 EMT[1]。
AXL-IN-13 (0-3 μM，24 小时) 抑制 TGF-β1 (10 ng/mL) 诱导的 MDA-MB-231 细胞迁移和侵袭[1]。
Western Blot Analysis[1] | Cell Line: | MDA-MB-231 cells | | Concentration: | 0, 0.11, 0.33, 1, 3 μM. | | Incubation Time: | 3 days | | Result: | Restored the protein levels of E-cadherin and N-cadherin to control levels. |
Cell Migration Assay[1] | Cell Line: | MDA-MB-231 cell | | Concentration: | 0, 0.11, 0.33, 1, 3 μM. | | Incubation Time: | 24 h | | Result: | Inhibited cell migration at 1 and 3 μM.
Inhibited the invasion of MDA-MB-231 cells by 22.6, 34.8, 56.5, and 70.4% at the concentrations of 0.11, 0.33, 1.0, and 3.0 μM, respectively. |
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体内研究
(In Vivo) | AXL-IN-13 (化合物 6li) (50 或 100 mg/kg，口服，14 天) 抑制 4T1 肿瘤生长和转移[1]。
AXL-IN-13 (25 mg/kg, 口服) 显示出较好的 PK 曲线，AUC 为 8410.21 ng/mL/h，T1/2值为 4.22 h，口服生物利用度 (F) 为 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) | 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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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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