Glesatinib hydrochloride (MGCD265 hydrochloride) 是一种具有口服活性的,有效的MET/SMO双抑制剂。 Glesatinib hydrochloride 是一种酪氨酸激酶抑制剂,可拮抗非小细胞肺癌 (NSCLC) 中 P 糖蛋白介导的多药耐药性 (MDR)。
生物活性 | Glesatinib hydrochloride (MGCD265 hydrochloride) is an orally active, potentMET/SMOdual inhibitor. Glesatinib hydrochloride, a tyrosine kinase inhibitor, antagonizesP-glycoprotein(P-gp) mediated multidrug resistance (MDR) in non-small cell lungcancer(NSCLC)[1][2]. |
体外研究 (In Vitro) | Glesatinib hydrochloride (MGCD265 hydrochloride; 0.01-5 μM; for 72 hours) results in a dose-dependent inhibition of cancer cell growth and shows the low IC50value of 0.08 μM on NSCLC H1299 cells[1]. Glesatinib hydrochloride (0.01, 0.1, 0.5, 1 μM) significantly increases by several-fold the percentage of apoptotic cells in NSCLC H1299 cells[1]. Glesatinib hydrochloride has the cytotoxicity to P-gp overexpressing cancer cells KB-C2, SW620/Ad300, HEK293/ABCB1, and their parent cells KB-3-1, SW620, HEK293 cells with the IC50s fell between 5 and 10 μM[1]. Glesatinib hydrochloride (1, 3 μM; 120 mins) increases the intracellular [3H]-Paclitaxel accumulation and inhibits [3H]-Paclitaxel efflux in cancer cell lines overexpressing P-gp[2]. Glesatinib hydrochloride (0-40 μM) stimulates the ATPase activity of P-gp transporters in a dose-dependent manner[2].
Cell Proliferation Assay[1] Cell Line: | NSCLC H1299 cells | Concentration: | 0.01, 0.1, 1, 2, 5 μM | Incubation Time: | For 72 hours | Result: | Resulted in a dose-dependent inhibition of cancer cell growth and showed the lowest IC50value of 0.08 μM. |
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体内研究 (In Vivo) | Glesatinib hydrochloride (MGCD265 hydrochloride; 15 mg/kg/day; orally; 40 weeks) causes a significant decrease in tumor size[1].
Animal Model: | 4–6-week old female balb/c athymic (nu/nu) mice with HCC827 NSCLC tumor xenografts[1] | Dosage: | 15 mg/kg | Administration: | Orally; daily; 40 weeks | Result: | Caused a significant decrease in tumor size. |
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运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | 4°C, sealed storage, away from moisture *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture) |
溶解性数据 | In Vitro: DMSO : 50 mg/mL(76.20 mM;Need ultrasonic) H2O :< 0.1 mg/mL (ultrasonic;warming;heat to 60℃)(insoluble) 配制储备液 1 mM | 1.5240 mL | 7.6200 mL | 15.2400 mL | 5 mM | 0.3048 mL | 1.5240 mL | 3.0480 mL | 10 mM | 0.1524 mL | 0.7620 mL | 1.5240 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 储备液的保存方式和期限:-80℃, 6 months; -20℃, 1 month (sealed storage, away from moisture)。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液,再依次添加助溶剂: ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用;
以下溶剂前显示的百 分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂: 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.5 mg/mL (3.81 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (3.81 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂: 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.5 mg/mL (3.81 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (3.81 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。 3. 请依序添加每种溶剂: 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (3.81 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (3.81 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。 *以上所有助溶剂都可在本网站选购。
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