GLPG1690 (Synonyms: Ziritaxestat) |
カタログ番号GC19168
One-Click Copy Product Info
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GLPG1690（Ziritaxestat）は、IC50 131 nM、Ki 15nMの新規オートタキシン（ATX）阻害剤である。特発性肺線維症の進行を効果的に阻止する
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1628260-79-6
Sample solution is provided at 25 µL, 10mM.
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GLPG1690（Ziritaxestat）は、IC50 131 nM、Ki 15nMの新規オートタキシン（ATX）阻害剤である。特発性肺線維症の進行を効果的に阻止する。
GLPG1690 (20 nM; 68-96h)は、ATXが発現上昇しているTSC2欠損細胞の増殖を阻害する。さらに、GLPG1690 は TSC2 欠損細胞の遊走およびアンカレッジ非依存性増殖を抑制する。
GLPG1690（50または100 mg/kg、12時間毎、19日間）は、マウスの血漿中ATX活性およびリゾホスファチジン酸（LPA）濃度を低下させる。さらに、GLPG1690 は、放射線照射と併用すると、in vivo でのがん細胞増殖の抑制を増強する。GLPG1690は、マウスにおいてリゾホスファチジルコリン（LPC）誘発性の内皮機能障害を回復させる。
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.
| 細胞実験[1]: | |
細胞株 | (ヒト腎血管筋脂肪腫由来）TSC2欠損細胞 |
準備方法 | 細胞を所定濃度のGLPG1690(Ziritaxestat)で処理した。 |
反応条件 | 20 nM; 68-96h |
アプリケーション | GLPG1690 は、ATX が過剰発現している TSC2 欠損細胞の増殖を阻害する。 |
| 動物実験 [2]: | |
動物モデル | BALB/cマウス（4T1腫瘍モデル） |
準備方法 | GLPG1690を乳鉢で微粉砕し、0.5%メチルセルロースに10 mg/mLの濃度で懸濁した。マウスにGLPG1690を50または100 mg/kgの用量で、10 mL/kg体重で経口投与した。対照マウスには0.5%メチルセルロースのビークルを投与した。 |
投与形態 | i.g; 50または100 mg/kg；12時間ごと、19日間 |
アプリケーション | GLPG1690は、血漿中ATX活性およびリゾホスファチジン酸（LPA）濃度を低下させる。 |
参考文献: [1]: 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. [2]: 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. | |
| Cas No. | 1628260-79-6 | SDF | |
| 同義語 | 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 | ||
| Formula | C30H33FN8O2S | M.Wt | 588.7 |
| 溶解度 | DMSO : 41.67 mg/mL (70.78 mM);Water : < 0.1 mg/mL (insoluble) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.6987 mL | 8.4933 mL | 16.9866 mL |
| 5 mM | 339.7 μL | 1.6987 mL | 3.3973 mL |
| 10 mM | 169.9 μL | 849.3 μL | 1.6987 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 34 reference(s) in Google Scholar.)