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| 5mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
Firategrast (formerly SB683699; T0047; SB-683699; T-0047) is a novel, potent and orally bioavailable alpha4 beta1/alpha4 beta7 (α4β1/α4β7) integrin antagonist designed to reduce trafficking of lymphocytes into the central nervous system (CNS). Thus, it is used as a drug for the treatment of multiple sclerosis (MS) which is found to be caused by the migration of leucocytes (such as monocytes, T cells, B cells and dendritic cells) into CNS. Firategrast could decrease multiple sclerosis (MS) activity, but may compromise CNS immune surveillance. Firategrast treatment was associated with modest decreases in median CSF total, CD4, CD8 and CD19 lymphocyte counts. The generally small magnitude of decreases suggests that sufficient numbers of lymphocytes can access the subarachnoid space, preserving CNS immune surveillance.
| ln Vitro |
Firategrast (0.1–10 µM; 1 hour) dramatically lowers the adhesion of CLL (chronic lymphocytic leukemia) cells[2]. Firategrast is an effective inhibitor of Integrin α4β1 (VLA-4) with an IC50 value of 198 nM. It works by preventing soluble VCAM/Fc chimeric protein (sVCAM-1) from attaching itself to G2 acute lymphoblastic leukemia (ALL) cells. CD49d (α4) and CD29 (β1) make up VLA-4[1][4].
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| ln Vivo |
Leukemic cells in the spleen are generally reduced when firategrast (30 mg/kg/day in drinking water; starting 2 or 7 days post transplantation and continuing for 21 days) is administered[3].
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| Animal Protocol |
Animal/Disease Models: Female Wild-type C57BL/6J mice (8 -12 weeks) with primary TCL1-tg splenocytes[3]
Doses: 30 mg/kg Route of Administration: Drinking water; daily; starting 2 or 7 days post transplantation to 21 days Experimental Results: demonstrated an overall reduction of leukemic cells in the spleen, accompanied by significant spleen weight reduction. |
| References |
[1]. Moses O. Evbuomwan, et al. Generation and Characterization of Novel VLA-4 Inhibitors for Stem Cell Mobilization in Combination with a CXCR2 Agonist. Blood (2017) 130 (Supplement 1): 3197.
[2]. Sarah E M Herman, et al. Treatment with Ibrutinib Inhibits BTK- and VLA-4-Dependent Adhesion of Chronic Lymphocytic Leukemia Cells In Vivo. Clin Cancer Res. 2015 Oct 15;21(20):4642-51. [3]. Eva Szenes, et al. TCL1 transgenic mice as a model for CD49d-high chronic lymphocytic leukemia. Leukemia. 2020 Sep;34(9):2498-2502. [4]. H Rahimi, et al. Aberrant regulation of the integrin very late antigen-4 in systemic lupus erythematosus. Lupus. 2013 Mar;22(3):297-306. |
| Molecular Formula |
C27H27F2NO6
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| Molecular Weight |
499.5
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| CAS # |
402567-16-2
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| Related CAS # |
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| SMILES |
O=C(O)[C@@H](NC(C1=C(F)C=CC=C1F)=O)CC2=CC=C(C3=C(OC)C=C(COCC)C=C3OC)C=C2
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| Synonyms |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 0.2 mg/mL (0.40 mM) in 1% SBE-beta-CD (add these co-solvents sequentially from left to right, and one by one), clear solution; with heating and sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0020 mL | 10.0100 mL | 20.0200 mL | |
| 5 mM | 0.4004 mL | 2.0020 mL | 4.0040 mL | |
| 10 mM | 0.2002 mL | 1.0010 mL | 2.0020 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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