ODM-203 是一种口服有效的，具有选择性的FGFR/VEGFR抑制剂，其对FGFR3/1/2和VEGFR3/2/1/4的IC50值分别为 6, 11, 16, 5, 9, 26 和 35 nM。ODM-203 具有很强的抗肿瘤活性，并能激活肿瘤微环境中的免疫反应。
| 生物活性 | ODM-203 is an orally active and selectiveFGFR/VEGFRinhibitor withIC50values of 6, 11, 16, 5, 9, 26 and 35 nM forFGFR3/1/2andVEGFR3/2/1/4, respectively. ODM-203 has strong anti-tumour activity and activates immune responses in the tumour microenvironment[1]. |
| IC50& Target[1] | FGFR1 11 nM (IC50) | FGFR2 16 nM (IC50) | FGFR3 6 nM (IC50) | FGFR4 35 nM (IC50) | VEGFR1 26 nM (IC50) | VEGFR2 9 nM (IC50) | VEGFR3 5 nM (IC50) | DDR1 6 nM (IC50) | RET 8 nM (IC50) | SIK3 23 nM (IC50) | PDGFRa 35 nM (IC50) | MINK1 41 nM (IC50) | MAP4K4 49 nM (IC50) |
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体外研究
(In Vitro) | ODM-203 (eight-dose concentration series up to 3 μM; 96 h) potently inhibits FGFR signaling and proliferation in several FGFR-dependent cell lines[1].
ODM-203 (eight-dose concentration series up to 3 μM; 10 days) inhibits endothelial tubule formation[1].
ODM-203 (1, 10, 100, 1000 nM; 1 h) inhibiting FGFR and VEGFR cellular signaling in HUVEC cells[1].
Cell Viability Assay[1] | Cell Line: | H1581 (ATCC-CRL-5878), SNU16 (ATCC-CRL-5974) and RT4 (HTB2) cells | | Concentration: | Eight-dose concentration series up to 3 μM | | Incubation Time: | 96 h | | Result: | Suppressed cell proliferation in a dose-dependent manner in H1581 (IC50=104 nM), SNU16 (IC50=132 nM) and RT4 cells (IC50=192 nM). |
Cell Viability Assay[1] | Cell Line: | HUVECs and human umbilical vein endothelial cells (co-culture) | | Concentration: | Eight-dose concentration series up to 3 μM | | Incubation Time: | 10 days (media and test agents were replaced every 2-3 days) | | Result: | Inhibited endothelial tubule formation in a dose-dependent manner at non-toxic concentrations with an IC50value of 33 nM. |
Western Blot Analysis[1] | Cell Line: | HUVEC cells | | Concentration: | 1, 10, 100, 1000 nM | | Incubation Time: | 1 h | | Result: | Suppressed both FGFR and VEGFR signaling. |
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体内研究
(In Vivo) | ODM-203 (20, 40 mg/kg; p.o.; single daily for 21 days) inhibits FGFR phosphorylation and tumor growth in several FGFR-dependent xenografts by suppressing FGFR signaling in tumors[1].
ODM-203 (7, 20, 40 mg/kg; p.o.; single daily for 21 days) shows strong anti-tumor activity in a VEGFR-dependent angiogenic orthotopic syngenic model (Renca) and suppresses angiogenesis[1].
ODM-203 (20, 40 mg/kg; p.o.; single daily for 5 days) activates immune response in the tumor microenvironment[1].
| Animal Model: | Athymic Nude-Foxn1nu female mice (9-week-old; subcutaneous xenograft models)[1]. | | Dosage: | 20, 40 mg/kg | | Administration: | Oral administration; single daily for 21 days. | | Result: | Significantly inhibited tumour growth for 21 consecutive days.
Showed tumor growth inhibition (TGI) in RT4 xenografts was 37% and 92% with dosage of 20 and 40 mg/kg, respectively. |
| Animal Model: | Male balb/c mice (8-week-old; orthotopic renca syngenic model)[1]. | | Dosage: | 7, 20, 40 mg/kg | | Administration: | Oral administration; single daily for 21 days. | | Result: | Showed tumor growth inhibition were 39%, 58% and 75% for dosage of 7, 20 and 40 mg/kg, respectively.
Inhibited formation of lung metastasis, and suppressed angiogenesis. |
| Animal Model: | Male balb/c male mice (5 to 7-week-old; renca subcutaneous tumor model)[1]. | | Dosage: | 20, 40 mg/kg | | Administration: | Oral administration; single daily for 5 days. | | Result: | Resulted in an increase in the percentage of total and CD4 T cells.
Decreased the expression of immune check points PD-1 and PD-L1 and increased IFN-γ expression on both CD8 T cells and NK cells. |
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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 : 66.67 mg/mL(131.88 mM;Need ultrasonic) 配制储备液 | 1 mM | 1.9781 mL | 9.8904 mL | 19.7808 mL | | 5 mM | 0.3956 mL | 1.9781 mL | 3.9562 mL | | 10 mM | 0.1978 mL | 0.9890 mL | 1.9781 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: ≥ 2.08 mg/mL (4.11 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.11 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.8 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: ≥ 2.08 mg/mL (4.11 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.11 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.8 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: ≥ 2.08 mg/mL (4.11 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.11 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 20.8 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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