| 生物活性 | Dovitinib (CHIR-258) is an orally active, potentmulti-targeted tyrosine kinase (RTK)inhibitor withIC50s of 1, 2, 36, 8/9, 10/13/8, 27/210 nM forFLT3,c-Kit,CSF-1R,FGFR1/FGFR3,VEGFR1/VEGFR2/VEGFR3andPDGFRα/PDGFRβ, respectively. Dovitinib has potent antitumor activity[1][2]. |
| IC50& Target[1] | FLT3 1 nM (IC50) | c-Kit 2 nM (IC50) | FGFR1 8 nM (IC50) | FGFR3 9 nM (IC50) | VEGFR3 8 nM (IC50) | VEGFR1 10 nM (IC50) | VEGFR2 13 nM (IC50) | PDGFRβ 27 nM (IC50) | PDGFRα 210 nM (IC50) | CSF-1R 36 nM (IC50) |
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体外研究
(In Vitro) | Dovitinib (CHIR-258) shows more than 10-fold inhibition InsR (IC50=2 μM), EGFR1 (IC50=2 μM), c-Met (IC50>3 μM), EphrinA2 (EphA2; IC50=4 μM), Tie2 (IC50=4 μM), IGFR1 (IC50>10 μM), and HER2 (IC50>10 μM)[1].
Dovitinib (12.5-400 nM; 48 hours) potently inhibits the FGF-stimulated growth of WT and F384L-FGFR3-expressing B9 cells with IC50 values of 25 nM[1].
Dovitinib (100, 500 nM; 96 hours) inhibits FGF-mediated ERK1/2 phosphorylation and induces apoptosis of FGFR3-expressing human myeloma cell lines[1].
Dovitinib (72 hours) inhibits cell proliferation of KMS11 (FGFR3-Y373C), OPM2 (FGFR3-K650E), and KMS18 (FGFR3-G384D) cells with IC50 of values of 90 nM (KMS11 and OPM2) and 550 nM, respectively[1].
Dovitinib (100 nM) augments Dexamethasone (0.5 μM) cytotoxicity in KMS11 cells[1].
Dovitinib significantly reduces the basal phosphorylation levels of FGFR-1, FGFR substrate 2α (FRS2-α) and ERK1/2 but not Akt in both SK-HEP1 and 21-0208 cells[2].
Dovitinib enhances the BMP-2-induced alkaline phosphatase (ALP) induction, which is a representative marker of osteoblast differentiation. Dovitinib also stimulates the translocation of phosphorylated Smad1/5/8 into the nucleus and phosphorylation of mitogen-activated protein kinases, including ERK1/2 and p38[3].
Dovitinib strongly inhibits both the interaction of TNIK with ATP (Ki, 13 nM) and the activation of Wnt signaling effectors such as β-catenin and TCF4. Dovitinib also induces caspase-dependent apoptosis in IM-9 cells without significant cytotoxicity in PBMCs[4].
Cell Viability Assay[1] | Cell Line: | WT and F384L-FGFR3-expressing B9 cells | | Concentration: | 12.5, 25, 50, 100, 200, 300, 400 nM | | Incubation Time: | 48 hours | | Result: | Potently inhibited the FGF-stimulated growth of the cells. |
Apoptosis Analysis[1] | Cell Line: | KMS11, OPM2, and KMS18 cells | | Concentration: | 100 nM or 500 nM | | Incubation Time: | 96 hours | | Result: | Induced apoptosis of FGFR3-expressing human myeloma cell lines. |
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体内研究
(In Vivo) | Dovitinib (CHIR-258; 10-60 mg/kg/day; gavage; for 21 days) has a significant antitumor effect[1].
Dovitinib (50 and 75 mg/kg) results in 97% and 98% tumor growth inhibition, respectively, and the maximal efficacy is at 50 mg/kg[2].
| Animal Model: | 6- to 8-week-old female BNX mice with KMS11 cells[1] | | Dosage: | 10, 30, 60 mg/kg | | Administration: | Gavage; daily for 21 days | | Result: | Had a significant antitumor effect in all 3 dose groups with 48%, 78.5%, and 94% growth inhibition in the 10 mg/kg, 30 mg/kg, and 60 mg/kg treatment. |
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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 : 25 mg/mL(63.71 mM;Need ultrasonic and warming) 配制储备液 | 1 mM | 2.5482 mL | 12.7411 mL | 25.4823 mL | | 5 mM | 0.5096 mL | 2.5482 mL | 5.0965 mL | | 10 mM | 0.2548 mL | 1.2741 mL | 2.5482 mL |
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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： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.5 mg/mL (6.37 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (6.37 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 (6.37 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (6.37 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 (6.37 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (6.37 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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