GLPG1690 (Synonyms: Ziritaxestat) |
Catalog No.GC19168
One-Click Copy Product Info
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GLPG1690(Ziritaxestat) est un nouveau inhibiteur de l'autotaxine, sa valeur d'IC50 est 131nM et celle de Ki est 15nM. Ce qui arrête efficacement la progression de la fibrose pulmonaire idiopathique.
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) est un nouveau inhibiteur de l'autotaxine, sa valeur d'IC50 est 131nM et celle de Ki est 15nM. Ce qui arrête efficacement la progression de la fibrose pulmonaire idiopathique[1-2].
GLPG1690 (20 nM; 68-96h) inhibe la prolifération des cellules TSC2 - déficientes où la régulation d'ATX est augmentée. D'ailleur, GLPG1690 supprime la migration et la croissance ancrage-indépendante des cellules TSC2-déficientes[3].
GLPG1690(i.g; 50 ou 100 mg/kg; toutes les 12 heures pendant 19 jours) réduit l'activité d' ATX plasmatique et la concentration en acide lysophosphatidique (LPA) dans les rats. De plus, GLPG1690 renforce l'inhibition de la prolifération cellulaire cancéreuse in vivo quand ce qui est combiné à l'irradiation[4]. GLPG1690 annule la dysfonction endothéliale lysophosphatidylcholine (LPS) - induite dans les rats[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.
| Expériences cellulaires [1]: | |
Lignées cellulaires | Cellules TSC2 - déficientes ( angiomyolipome rénal humain - dérvées) |
Méthode de préparation | Les cellules ont été traitées par GLPG1690 à la concentration spécifiée (Ziritaxestat). |
Conditions de réaction | 20 nM; 68-96h |
Domaines d'application | GLPG1690 inhibe la croissance des cellules TSC2-déficientes où ATX est surexprimé. |
| Expériences animales [2]: | |
Modèles animaux | Rats BALB/c (modèle tumoral 4T1) |
Méthode de préparation | GLPG1690 a été finement moulu dans un mortier et a été suspendu à la concentration de 10 mg/mL dans 0,5% méthylcellulose. Les rats ont été administrés par GLPG1690 par gavage aux doses de 50 ou 100 mg/kg, le volume de gavage est 10 mL/kg de poids corporel. Les rats de témoin ont été administrés par véhicule qui est 0,5% méthylcellulose |
Forme de dosage | i.g;50 ou 100 mg/kg; toutes les 12 heures pendant 19 jours |
Domaines d'application | GLPG1690 réduit l'activité d'ATX plasmatique et la concentration en acide lysophosphatidique (LPA). |
References: | |
| Cas No. | 1628260-79-6 | SDF | |
| Synonymes | 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 |
| Solubility | 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
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.)