Tasquinimod
(Synonyms: 他喹莫德; ABR-215050) 目录号 : GC14340
An orally-active anti-cancer compound
Cas No.:254964-60-8
Sample solution is provided at 25 µL, 10mM.
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Tasquinimod is an orally administered quinoline-3-carboxamide with potent antiangiogenic and antitumorigenic ability that has shown promise in the treatment of advanced prostate cancers [1].
Treatment with tasquinimod leads to a remarkable up-regulation in the expression of TSP-1 and down-regulation of VEGF and HIF-1α. The antiangiogenic activities of tasquinimod are therefore due to the dual inhibition of S100A9/TLR4 in MDSCs and the inhibition of HDAC4/N-CoR/HDACs deacetylation of HIF1-α in both endothelial and tumor cells, inhibiting hypoxia induced angiogenesis.
Human endothelial and prostate cancer cells in culture and human prostate cancer xenografts growing in castrated male nude mice were evaluated for their response to radiation alone and in combination with tasquinimod. Due to its potent reduction of the hypoxic response in endothelial cells, cancer cells, TAMs and MDSCs, tasquinimod inhibits tumor angiogenesis while sparing already formed vasculature. The data obtained in vivo and in vitro highlights a potent anticancer effect as a monotherapy in addition to greatly improving the response to combination therapies with docetaxel, androgen deprivation therapy or radiotherapy [1, 3].
At clinically relevant drug levels, tasquinimod significantly enhances anti-cancer efficacy of fractionated radiation with optimal timing for initiating daily tasquinimod treatment being after completion of the fractionated radiation. Phase I and II studies of tasquinimod have demonstrated tasquinimod to be well-tolerated and lead to significant improvements in progression-free survival from metastasis, by a period of 4.3 months, in patients with minimally symptomatic CRPC. The result highlights tasquinimod as an extremely promising and much needed therapeutic tool for use in CRPC [1, 2].
References:
[1]. Williamson SC, Hartley AE, Heer R. A review of tasquinimod in the treatment of advanced prostate cancer. Drug Design Development And Therapy, 2013, 7: 167-174.
[2]. Olsson A, Bjork A, Vallon-Christersson J, et al. Tasquinimod (ABR-215050), a quinoline-3-carboxamide anti-angiogenic agent, modulates the expression of thrombospondin-1 in human prostate tumors. Molecular Cancer, 2010, 9: 107.
[3]. Dalrymple SL, Becker RE, Zhou HM, et al. Tasquinimod prevents the angiogenic rebound induced by fractionated radiation resulting in an enhanced therapeutic response of prostate cancer xenografts. Prostate, 2012, 72(6): 638-648.
| Cell experiment [1]: | |
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Cell lines |
LNCaP cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
24 h; 50 μM |
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Applications |
Generated microarray data based on four separate biological replicates showed a drug-induced effect of 50μM tasquinimod on gene expression in LNCaP cells when cultured in vitro for 24 h. The expression data achieved by RT-PCR were consistent with the microarray analysis data with a significant up-regulation of THBS1, GDF15 and CYP1A1 whereas CXCR4 and AGER1 did not change expression significantly. |
| Animal experiment [2]: | |
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Animal models |
Male athymic Nude BALB/c mice (age 8 weeks) |
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Dosage form |
10 mg/kg /day; oral taken |
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Applications |
To investigate whether an early treatment could inhibit tumor establishment in addition to the previously shown effects on tumor growth, treatment was initiated directly at subcutaneous inoculation of LNCaP cells and compared to treatment starting 1 week after inoculation, when tumor growth already was established. In the control group the take rate was 100%. By direct treatment the tumor take rate was decreased to 12.5 % by tasquinimod (10 mg/kg/day) compared to 87.5% in the group treated from 1 week after inoculation (P |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Olsson A, Björk A, Vallon-Christersson J, et al. Research Tasquinimod (ABR-215050), a quinoline-3-carboxamide anti-angiogenic agent, modulates the expression of thrombospondin-1 in human prostate tumors[J]. 2010. [2] Jennbacken K, Welen K, Olsson A, et al. Inhibition of metastasis in a castration resistant prostate cancer model by the quinoline‐3‐carboxamide tasquinimod (ABR‐215050)[J]. The Prostate, 2012, 72(8): 913-924. |
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| Cas No. | 254964-60-8 | SDF | |
| 别名 | 他喹莫德; ABR-215050 | ||
| 化学名 | 4-hydroxy-5-methoxy-N,1-dimethyl-2-oxo-N-[4-(trifluoromethyl)phenyl]quinoline-3-carboxamide | ||
| Canonical SMILES | CN1C2=C(C(=CC=C2)OC)C(=C(C1=O)C(=O)N(C)C3=CC=C(C=C3)C(F)(F)F)O | ||
| 分子式 | C20H17F3N2O4 | 分子量 | 406.36 |
| 溶解度 | ≥ 20.318 mg/mL in DMSO, ≥ 4.75 mg/mL in EtOH with ultrasonic and warming | 储存条件 | Store at -20°C |
| General tips | 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°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4609 mL | 12.3044 mL | 24.6087 mL |
| 5 mM | 0.4922 mL | 2.4609 mL | 4.9217 mL |
| 10 mM | 0.2461 mL | 1.2304 mL | 2.4609 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet