| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 50mg | |||
| 100mg | |||
| Other Sizes |
| Targets |
Lifitegrast targets the integrin lymphocyte function-associated antigen-1 (LFA-1) on T cells. By blocking the interaction between LFA-1 and its ligand ICAM-1, it prevents T cell adhesion and subsequent inflammatory signaling.
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| ln Vitro |
Lifitegrast (SAR 1118) reduces the total inflammatory response by inhibiting the binding of two crucial cell surface proteins, lymphocyte function-associated antigen 1 and intercellular adhesion molecule 1, which in turn decreases T cell-mediated inflammation [1]. With an IC50 of 2.98 nM, liditelegrast potently prevents Jurkat T cell adhesion to ICAM-1[1].
In vitro, Lifitegrast sodium inhibits Jurkat T cell attachment to ICAM-1 with an IC50 of 2.98 nM. It inhibits the secretion of key inflammatory cytokines, including T-cell regulating cytokines IL-2 and IL-4 and several other cytokines associated with the clinical severity of dry eye (IL-1α, IL-1β, IL-10, IFN-γ, MIP-1α and TNF-α). |
| ln Vivo |
When silicone hydrogel lenses are present, ligifegrast exhibits strong anti-inflammatory efficacy against corneal irritation brought on by antibiotic-killed Pseudomonas aeruginosa and Staphylococcus aureus. The best dosage is two or three pre-applies of 1% solution[2].
In vivo, Lifitegrast has potent anti-inflammatory activity on corneal inflammation induced by antibiotic-killed P. aeruginosa and S. aureus in the presence of a silicone hydrogel lens. Topical ocular administration (≥0.1%) reduces neutrophil infiltration to the corneal stroma in a mouse model of corneal inflammation. In clinical studies, lifitegrast 5.0% significantly improves clinical signs and biomarkers in dry eye disease within 12 weeks of treatment. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays typically measure the displacement of a radiolabeled ligand or the inhibition of cell adhesion. For Lifitegrast, binding to LFA-1 is assessed using surface plasmon resonance or ELISA-based methods to determine the IC50 for inhibition of ICAM-1/LFA-1 interaction.
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| Cell Assay |
In vitro cellular assays evaluate the antiproliferative or anti-inflammatory effects of Lifitegrast using human T-cell lines such as Jurkat cells. Cells are cultured and treated with varying concentrations of the compound, and adhesion to ICAM-1-coated plates is measured. The IC50 is calculated from dose-response curves. Cytokine secretion profiles are also assessed via ELISA.
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| Animal Protocol |
In vivo animal experiments are conducted in mouse models of corneal inflammation. Lifitegrast is administered topically as an ophthalmic solution at concentrations of 0.1% to 5%, and corneal inflammation is assessed by measuring neutrophil infiltration and inflammatory cytokine levels. Efficacy in diabetic retinopathy models has also been explored using rat models.
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| ADME/Pharmacokinetics |
Lifitegrast sodium has a molecular formula of C29H23Cl2N2NaO7S and a molecular weight of 637.46. When administered as a 5% ophthalmic solution, it is rapidly absorbed into the plasma with a mean Tmax of 0.09 hours, but systemic exposure is extremely low (Cmax = 1.70 ng/mL). The compound is highly bound to plasma proteins (98.9%) and is minimally metabolized by CYP enzymes, with excretion primarily via feces.
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| Toxicity/Toxicokinetics |
In preclinical safety studies, Lifitegrast showed no relevant inhibition of key CYP isozymes at therapeutic concentrations. Long-term postmarketing analysis confirms its safety for dry eye treatment, showing no new safety signals in nearly 800,000 patient treatment-years. Common adverse effects are typically ocular in nature, such as instillation site irritation.
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| References |
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| Additional Infomation |
Lifitegrast sodium is the sodium salt form of Lifitegrast, a tetrahydroisoquinoline derivative and an antagonist of lymphocyte function-associated antigen-1 (LFA-1), available as an ophthalmic solution for the treatment of dry eye syndrome (DED; dry keratoconjunctivitis; dry eye syndrome). Although the exact mechanism of action of Lifitegrast in treating dry eye is not fully elucidated, after intraocular administration, it targets and binds to integrin LFA-1 (a protein present on the surface of leukocytes). This prevents the interaction between LFA-1 and its ligand, intercellular adhesion molecule-1 (ICAM-1). Since ICAM-1 may be overexpressed in the corneal and conjunctival tissues of patients with dry eye, blocking the LFA-1/ICAM-1 interaction with Lifitegrast may inhibit T cell adhesion to ICAM-1 and potentially block the formation of immune synapses. This may prevent T cell proliferation, activation, and migration in the corneal and conjunctival tissues, as well as the release of pro-inflammatory cytokines. This may reduce inflammation, protect the corneal surface from inflammation-mediated damage, and alleviate symptoms of dry eye.
Lifitegrast was approved by the U.S. FDA in July 2016 for the treatment of signs and symptoms of dry eye disease. It is also known by the synonyms SAR-1118 and SHP-606. The compound is supplied as a 5% ophthalmic solution for twice-daily dosing. The EMA marketing authorization application was withdrawn in June 2020. |
| Molecular Formula |
C29H23CL2N2NAO7S
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|---|---|
| Molecular Weight |
637.46289563179
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| Exact Mass |
636.05
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| CAS # |
1119276-80-0
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| Related CAS # |
Lifitegrast;1025967-78-5
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| PubChem CID |
56963348
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
6.233
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
42
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| Complexity |
1110
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CS(=O)(=O)C1=CC=CC(=C1)C[C@@H](C(=O)[O-])NC(=O)C2=C(C=C3CN(CCC3=C2Cl)C(=O)C4=CC5=C(C=C4)C=CO5)Cl.[Na+]
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| InChi Key |
BPWOKOSRORLLIN-BQAIUKQQSA-M
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| InChi Code |
InChI=1S/C29H24Cl2N2O7S.Na/c1-41(38,39)20-4-2-3-16(11-20)12-23(29(36)37)32-27(34)25-22(30)13-19-15-33(9-7-21(19)26(25)31)28(35)18-6-5-17-8-10-40-24(17)14-18;/h2-6,8,10-11,13-14,23H,7,9,12,15H2,1H3,(H,32,34)(H,36,37);/q;+1/p-1/t23-;/m0./s1
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| Chemical Name |
sodium
(S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoate
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| Synonyms |
SAR-1118 SAR 1118-023SAR 1118 SAR1118-02 SAR1118Lifitegrast sodium SAR-1118-023 Xiidra
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
H2O : ~100 mg/mL (~156.87 mM)
DMSO : ~100 mg/mL (~156.87 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.92 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (3.92 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5687 mL | 7.8436 mL | 15.6873 mL | |
| 5 mM | 0.3137 mL | 1.5687 mL | 3.1375 mL | |
| 10 mM | 0.1569 mL | 0.7844 mL | 1.5687 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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