GLPG1690 (Synonyms: Ziritaxestat) |
رقم الكتالوجGC19168
One-Click Copy Product Info
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GLPG1690 (GLPG1690) هو مثبط أوتوتاكسين (ATX) الأول في فئته ، مع IC50 من 131 نانومتر و Ki من 15 نانومتر.
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) 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.
| 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 | |
| المرادفات | 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 |
| الذوبان | 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 | |||
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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)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
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.)