GLPG1690
(Synonyms: Ziritaxestat) 目录号 : GC19168
GLPG1690(Ziritaxestat) 是一种新型的autotaxin (ATX)抑制剂，IC50为131 nM, Ki为15 nM。它能有效阻止特发性肺纤维化的进展。
Cas No.:1628260-79-6
Sample solution is provided at 25 µL, 10mM.
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GLPG1690(Ziritaxestat) is a novel autotaxin (ATX) inhibitor with an IC50 of 131 nM and a Ki of 15 nM. It effectively halts the progression of idiopathic pulmonary fibrosis [1-2].
GLPG1690 (20 nM; 68-96h) inhibits the proliferation of TSC2-deficient cells where ATX is upregulated. Additionally, GLPG1690 suppresses the migration and anchorage-independent growth of TSC2-deficient cells[3].
GLPG1690(i.g; 50 or 100 mg/kg; every 12 hours for 19 days) reduces plasma ATX activity and lysophosphatidic acid (LPA) concentration in mice. Furthermore, GLPG1690 enhances the inhibition of cancer cell proliferation in vivo when combined with irradiation[4]. GLPG1690 reverses lysophosphatidylcholine (LPC)-induced endothelial dysfunction in mice[5].
References:
[1]. Desroy N, Housseman C, et,al. Discovery of 2-[[2-Ethyl-6-[4-[2-(3-hydroxyazetidin-1-yl)-2-oxoethyl]piperazin-1-yl]-8-methylimidazo[1,2-a]pyridin-3-yl]methylamino]-4-(4-fluorophenyl)thiazole-5-carbonitrile (GLPG1690), a First-in-Class Autotaxin Inhibitor Undergoing Clinical Evaluation for the Treatment of Idiopathic Pulmonary Fibrosis. J Med Chem. 2017 May 11;60(9):3580-3590. doi: 10.1021/acs.jmedchem.7b00032. Epub 2017 May 1. PMID: 28414242.
[2]. Maher TM, van der Aar EM, et,al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of GLPG1690, a novel autotaxin inhibitor, to treat idiopathic pulmonary fibrosis (FLORA): a phase 2a randomised placebo-controlled trial. Lancet Respir Med. 2018 Aug;6(8):627-635. doi: 10.1016/S2213-2600(18)30181-4. Epub 2018 May 20. PMID: 29792287.
[3]. Feng Y, Mischler WJ, et,al. Therapeutic Targeting of the Secreted Lysophospholipase D Autotaxin Suppresses Tuberous Sclerosis Complex-Associated Tumorigenesis. Cancer Res. 2020 Jul 1;80(13):2751-2763. doi: 10.1158/0008-5472.CAN-19-2884. Epub 2020 May 11. PMID: 32393662; PMCID: PMC7335343.
[4]. Tang X, Wuest M, et,al. Inhibition of Autotaxin with GLPG1690 Increases the Efficacy of Radiotherapy and Chemotherapy in a Mouse Model of Breast Cancer. Mol Cancer Ther. 2020 Jan;19(1):63-74. doi: 10.1158/1535-7163.MCT-19-0386. Epub 2019 Sep 23. PMID: 31548293.
[5]. Janovicz A, Majer A, et,al. Autotaxin-lysophosphatidic acid receptor 5 axis evokes endothelial dysfunction via reactive oxygen species signaling. Exp Biol Med (Maywood). 2023 Oct;248(20):1887-1894. doi: 10.1177/15353702231199081. Epub 2023 Oct 14. PMID: 37837357; PMCID: PMC10792427.
GLPG1690(Ziritaxestat)是一种新型的autotaxin (ATX)抑制剂，IC50为131 nM, Ki为15 nM。它能有效阻止特发性肺纤维化的进展[1-2]。
GLPG1690(20 nM;68-96h)抑制ATX上调的TSC2缺陷细胞的增殖。此外，GLPG1690还能抑制TSC2缺陷细胞的迁移和不依赖锚定的生长[3]。
GLPG1690 (i.g; 50 or 100 mg/kg; every 12 hours for 19 days) 降低小鼠血浆ATX活性和溶血磷脂酸(LPA)浓度。此外，GLPG1690在体内与辐照联合使用时，可增强对癌细胞增殖的抑制作用[4]。GLPG1690逆转溶血磷脂酰胆碱(LPC)诱导的小鼠内皮功能障碍[5]。
| Cell experiment [1]: | |
Cell lines | (Human renal angiomyolipoma-derived) TSC2-deficient cells |
Preparation Method | Cell were treated with specified concentration GLPG1690(Ziritaxestat). |
Reaction Conditions | 20 nM; 68-96h |
Applications | GLPG1690 inhibits the growth of TSC2-deficient cells where ATX is overexpressed. |
| Animal experiment [2]: | |
Animal models | BALB/c mice (4T1 tumor model) |
Preparation Method | GLPG1690 was finely ground in a mortar and suspended at a concentration of 10 mg/mL in 0.5% methyl cellulose. Mice were administered GLPG1690 by gavage at doses of 50 or 100 mg/kg, using 10 mL/kg of body weight. Control mice received the vehicle, which was 0.5% methyl cellulose. |
Dosage form | i.g;50 or 100 mg/kg; every 12 hours for 19days |
Applications | GLPG1690 decreases the activity of plasma ATX and the concentration of lysophosphatidic acid (LPA). |
References: | |
| Cas No. | 1628260-79-6 | SDF | |
| 别名 | Ziritaxestat | ||
| Canonical SMILES | N#CC1=C(C2=CC=C(F)C=C2)N=C(N(C3=C(CC)N=C4C(C)=CC(N5CCN(CC(N6CC(O)C6)=O)CC5)=CN43)C)S1 | ||
| 分子式 | C30H33FN8O2S | 分子量 | 588.7 |
| 溶解度 | DMSO : 41.67 mg/mL (70.78 mM);Water : < 0.1 mg/mL (insoluble) | 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 | 1.6987 mL | 8.4933 mL | 16.9866 mL |
| 5 mM | 0.3397 mL | 1.6987 mL | 3.3973 mL |
| 10 mM | 0.1699 mL | 0.8493 mL | 1.6987 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: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet