GLPG1690 (Synonyms: Ziritaxestat) |
Katalog-Nr.GC19168
One-Click Copy Product Info
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GLPG1690(Ziritaxestat) ist ein neuartiger Autotaxin (ATX)-Inhibitor mit einem IC50 von 131 nM und einem Ki von 15 nM. Es stoppt effektiv das Fortschreiten der idiopathischen Lungenfibrose.
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) ist ein neuartiger Autotaxin (ATX)-Inhibitor mit einem IC50 von 131 nM und einem Ki von 15 nM. Es stoppt effektiv das Fortschreiten der idiopathischen Lungenfibrose [1-2].
GLPG1690 (20 nM; 68-96 Stunden) hemmt die Proliferation von TSC2-defizienten Zellen, bei denen ATX hochreguliert wird. Zusätzlich unterdrückt GLPG1690 das migrations- und verankerungsunabhängige Wachstum von TSC2-defizienten Zellen[3].
GLPG1690(i.g; 50 oder 100 mg/kg; alle 12 Stunden für 19 Tage) reduziert die ATX-Aktivität im Plasma und die Intensität von Lysophosphatidsäure (LPA) bei Mäusen. Darüber hinaus erhöht GLPG1690 kehrt die durch Lysophosphatidylcholin (LPC) induzierte endotheliale Dysfunktion bei Mäusen um[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.
| Zellexperiment [1]: | |
Zelllinien | (Von menschlichen renalen Angiomyolipom abgeleitet) TSC2-defiziente Zellen |
Vorbereitungsmethode | Die Zellen wurden mit einer bestimmten Konzentration GLPG1690 (Zirtaxetat) behandelt. |
Reaktionsbedingungen | 20 nM; 68-96 Stunden |
Anwendungen | GLPG1690 hemmt das Wachstum von TSC2-defizienten Zellen, bei denen ATX überexprimiert wird. |
| Tierversuch [2]: | |
Tiermodelle | BALB/c-Mäuse (4T1-Tumormodell) |
Vorbereitungsmethode | GLPG1690 wurde in einem Mörser fein gemahlen und in einer Konzentration von 10 mg/ml in 0,5% Methylcellulose suspendiert. Mäusen wurde GLPG1690 durch Sonde in Dosen von 50 oder 100 mg/kg Körpergewicht verwendet wurden. Kontrollmäuse erhielten das Vehikel, das aus 0,5% Methylcellulose bestand. |
Dosierungsform | i.g;50 oder 100 mg/kg; alle 12 Stunden für 19 Tage |
Anwendungen | GLPG1690 verringert die Aktivität von Plasma-ATX und die Konzentration von Lysophosphatidsäure (LPA). |
References: | |
| Cas No. | 1628260-79-6 | SDF | |
| Überlieferungen | 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 |
| Löslichkeit | 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)
g
μL
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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.)