Firategrast |
Catalog No.GC14804
One-Click Copy Product Info
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Firategrast is an orally bioavailable α4β1 (VLA-4) /α4β7 integrin antagonist.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 402567-16-2
Sample solution is provided at 25 µL, 10mM.
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Firategrast is an orally bioavailable α4β1 (VLA-4) /α4β7 integrin antagonist. Firategrast can inhibit the binding of integrins to related ligands, including vascular cell adhesion protein 1 (VCAM-1) and mucosal addressin cell adhesion molecule 1 (MAdCAM-1). Firategrast can reduce the migration of lymphocytes to the central nervous system (CNS) and decrease the activity of multiple sclerosis (MS)[1][2].
In vitro, treatment of Chronic Lymphocytic Leukemia Peripheral Blood Mononuclear Cells (CLL PBMCs) with Firategrast (500nM; 1h) significantly reduced CLL cells adhesion to fibronectin[3].
In vivo, Firategrast (30mg/kg/d; p.o.; days 2–21 or 7–21 post-transplantation) significantly reduced both the splenic leukemic burden and spleen weight in adoptive transfer CLL mouse model[4]. Firategrast (100mg/kg; i.v.; single dose) disrupted HSPC (Hematopoietic Stem and Progenitor Cell) –VCAM-1 adhesion in the bone marrow niche and subsequently elevated peripheral white blood cells (WBC) and colony-forming units in culture (CFU-C) counts in DBA/2J mice[5].
References:
[1] Grove RA, Shackelford S, Sopper S, et al. Leukocyte counts in cerebrospinal fluid and blood following firategrast treatment in subjects with relapsing forms of multiple sclerosis. Eur J Neurol. 2013;20(7):1032-1042.
[2] Miller D H, Weber T, Grove R, et al. Firategrast for relapsing remitting multiple sclerosis: a phase 2, randomised, double-blind, placebo-controlled trial. The Lancet Neurology, 2012, 11(2): 131-139.
[3] Herman SE, Mustafa RZ, Jones J, Wong DH, Farooqui M, Wiestner A. Treatment with Ibrutinib Inhibits BTK- and VLA-4-Dependent Adhesion of Chronic Lymphocytic Leukemia Cells In Vivo. Clin Cancer Res. 2015;21(20):4642-4651.
[4] Szenes E, Härzschel A, Decker S, et al. TCL1 transgenic mice as a model for CD49d-high chronic lymphocytic leukemia. Leukemia. 2020;34(9):2498-2502.
[5] Karpova D, Rettig MP, Ritchey J, et al. Targeting VLA4 integrin and CXCR2 mobilizes serially repopulating hematopoietic stem cells. J Clin Invest. 2019;129(7):2745-2759.
| Cell experiment [1]: | |
Cell lines | Chronic Lymphocytic Leukemia Peripheral Blood Mononuclear Cells (CLL PBMC) |
Preparation Method | PBMCs were plated at 107 cells/mL in 500µL into 24-well fibronectin coated plates. Cells were incubated with 500nM Firategrast for 1 hour at 37°C. The plates were centrifuged at 400×g for one minute and cells were left to adhere for 1 hour at 37°C. Non-adhered cells were removed by washing three times with PBS. Wells were imaged using the EVOS fl microscope. Quantification of the number of adhered CLL PBMCs was done using the Image J software. |
Reaction Conditions | 500nM; 1h |
Applications | Treatment of CLL PBMCs with Firategrast significantly reduced CLL cells adhesion to fibronectin |
| Animal experiment [2]: | |
Animal models | Adoptive transfer CLL mouse model |
Preparation Method | Adoptive transfer CLL mouse model :Wild-type C57BL/6J mice were transplanted intravenously with ~5 Mio splenocytes from a TCL1-tg mouse. Mice were treated with vehicle (0.9% NaCl; 1% HP-β-CD) or Firategrast, 30 mg/kg/d in drinking water, starting two or seven days post transplantation. Mice were sacrificed 21 days after transplantation. |
Dosage form | 30mg/kg/d; p.o.; 2-21d or 7-21d |
Applications | Firategrast-treated mice showed an overall reduction of leukemic cells in the spleen, accompanied by significant spleen weight reduction. |
References: | |
| Cas No. | 402567-16-2 | SDF | |
| Chemical Name | (2S)-2-[(2,6-difluorobenzoyl)amino]-3-[4-[4-(ethoxymethyl)-2,6-dimethoxyphenyl]phenyl]propanoic acid | ||
| Canonical SMILES | CCOCC1=CC(=C(C(=C1)OC)C2=CC=C(C=C2)CC(C(=O)O)NC(=O)C3=C(C=CC=C3F)F)OC | ||
| Formula | C27H27F2NO6 | M.Wt | 499.5 |
| Solubility | ≥ 50 mg/mL in DMSO, ≥ 90.8 mg/mL in EtOH with gentle warming | 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 | 2.002 mL | 10.01 mL | 20.02 mL |
| 5 mM | 400.4 μL | 2.002 mL | 4.004 mL |
| 10 mM | 200.2 μL | 1.001 mL | 2.002 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: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)