GLPG1690 (Synonyms: Ziritaxestat) |
Catalog No.GC19168
One-Click Copy Product Info
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GLPG1690(Ziritaxestat)는 IC50 131nM, Ki 15nM를 가지는 새로운 자세크리트 운동인자(ATX) 억제제이다. 이것은 특이성 폐섬유화의 진행을 효과적으로 멈추고 있다.
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)는 IC50 131nM, Ki 15nM를 가지는 새로운 자세크리트 운동인자(ATX) 억제제이다. 이것은 특이성 폐섬유화의 진행을 효과적으로 멈추고 있다.
GLPG1690(20nM; 68-96시간)은 ATX가 상승 조절되는 TSC2 결핍 세포의 증식을 억제한다. 또한 GLPG1690은 TSC2 결핍 세포의 이동과 댐핑 없이 자라는 성장을 억제한다[3].
GLPG1690(구강 투여; 50 또는 100 mg/kg; 12시간마다 19일간)은 쥐의 혈장에서ATX활성과 녹색 인산(LPA) 농도를 낮추었다. 또한 GLPG1690은 방사선치료와 결합하여 쥐 내에서 암세포 증식의 억제를 강화한다[4]. GLPG1690은 쥐에서 녹색 인산화 콜린(LPC)으로 인한 내피 기능 장애를 반전시켰다[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.
| 세포 실험 [1]: | |
세포 라인 | (인간 신장 혈관지방종의 세포에서 유래된) TSC2 결핍 세포 |
제조 방법 | 세포는 지정된 농도의 GLPG1690(Ziritaxestat)로 처리되었습니다. |
반응 조건 | 20 nM; 68-96시간 동안 |
응용 분야 | GLPG1690은 ATX가 과표현되는 TSC2 결핍 세포의 성장을 억제합니다. |
| 동물 실험 [2]: | |
동물 모형 | BALB/c 쥐 (4T1 암 모형) |
제조 방법 | GLPG1690은 모루에서 세게 분쇄되어 0.5% 메틸 셀룰로즈에서 10 mg/mL의 농도로 흩뿌렸습니다. 쥐는 구강 주사로 GLPG1690을 50 또는 100 mg/kg의 용량으로 투여받았으며, 체중에 따라 10 mL/kg의량으로 주었습니다. 대조군 쥐는 0.5% 메틸 셀룰로즈를 운반하였습니다. |
제형 | i.g;50 나 100 mg/kg; 19일 동안 매일 12시간 |
응용 분야 | GLPG1690은 혈장ATX활성과 녹색 인산(LPA) 농도를 낮추습니다. |
참고문헌: [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. | |
| Cas No. | 1628260-79-6 | SDF | |
| Synonyms | 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 | |||
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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.)