Sitravatinib (MGCD516) 是一种有口服活性的受体酪氨酸激酶 (RTK) 抑制剂。抑制 Axl,MER,VEGFR3,VEGFR2,VEGFR1,KIT,FLT3,DDR2,DDR1,TRKA,和 TRKB,IC50分别为 1.5 nM,2 nM,2 nM,5 nM,6 nM,6 nM,8 nM,0.5 nM,29 nM,5 nM,和 9 nM。Sitravatinib 单独使用即具有有效的抗肿瘤功效,且通过促进抗肿瘤免疫微环境增强了 PD-1 阻断的活性。
生物活性 | Sitravatinib (MGCD516) is an orally bioavailablereceptor tyrosine kinase (RTK)inhibitor withIC50s of 1.5 nM, 2 nM, 2 nM, 5 nM, 6 nM, 6 nM, 8 nM, 0.5 nM, 29 nM, 5 nM, and 9 nM for Axl, MER, VEGFR3, VEGFR2, VEGFR1, KIT,FLT3,DDR2,DDR1,TRKA,TRKB, respectively[1]. Sitravatinib shows potent single-agent antitumor efficacy and enhances the activity ofPD-1blockade through promoting an antitumor immune microenvironment[2]. |
IC50& Target | VEGFR3 2 nM (IC50) | VEGFR1 6 nM (IC50) | VEGFR2 5 nM (IC50) | TrkA 5 nM (IC50) | TrkB 9 nM (IC50) | DDR1 29 nM (IC50) | DDR2 0.5 nM (IC50) | Axl 1.5 nM (IC50) | MER 2 nM (IC50) | FLT3 8 nM (IC50) | KIT 6 nM (IC50) |
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体外研究 (In Vitro) | Sitravatinib (0.01 nM-10 μM; 14 days) reduces colony formation in a dose-dependent manner in KLN205 and E0771 cell lines[2]. Sitravatinib (0.001-10 μM; 5 days) inhibits tumor cell viability with IC50s of approximately 1 μM in KLN205, E0771 and CT1B-A5 cell lines[2].
Cell Viability Assay[2] Cell Line: | KLN205, E0771, CT1B-A5 cells | Concentration: | 0.001, 0.01, 0.1, 1, 10 μM | Incubation Time: | 5 days | Result: | Inhibited KLN205, E0771, CT1B-A5 cells with IC50s of approximately 1 μM. |
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体内研究 (In Vivo) | Sitravatinib (20 mg/kg; p.o.; once per day for 6 days) significantly inhibits tumor progression and induces tumor regression in C57BL/6 mice bearing CT1B-A5 cells model[2].
Animal Model: | 6-week-old C57BL/6 mice (bearing CT1B-A5 cells)[2] | Dosage: | 20 mg/kg | Administration: | Oral administration; once per day for 6 days | Result: | Significantly inhibited tumor progression and induced tumor regression. |
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运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | Powder | -20°C | 3 years | | 4°C | 2 years | In solvent | -80°C | 6 months | | -20°C | 1 month |
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溶解性数据 | In Vitro: DMSO : ≥ 32 mg/mL(50.82 mM) *"≥" means soluble, but saturation unknown. 配制储备液 1 mM | 1.5881 mL | 7.9405 mL | 15.8811 mL | 5 mM | 0.3176 mL | 1.5881 mL | 3.1762 mL | 10 mM | 0.1588 mL | 0.7941 mL | 1.5881 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。-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: 5% DMSO 40%PEG300 5%Tween-80 50% saline Solubility: 2.75 mg/mL (4.37 mM); Suspended solution; Need ultrasonic 2. 请依序添加每种溶剂: 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: 2.5 mg/mL (3.97 mM); Suspended solution; Need ultrasonic
此方案可获得 2.5 mg/mL (3.97 mM) 的均匀悬浊液,悬浊液可用于口服和腹腔注射。 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。 3. 请依序添加每种溶剂: 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: 2.5 mg/mL (3.97 mM); Suspended solution; Need ultrasonic
此方案可获得 2.5 mg/mL (3.97 mM) 的均匀悬浊液,悬浊液可用于口服和腹腔注射。 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。 4. 请依序添加每种溶剂: 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (3.97 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (3.97 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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