Synonym
Lifitegrast sodium; SAR-1118-023; SAR 1118-023; SAR1118-02; SAR-1118; SAR 1118; SAR1118; Xiidra;
IUPAC/Chemical Name
sodium (S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoate
InChi Key
BPWOKOSRORLLIN-BQAIUKQQSA-M
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
SMILES Code
CS(=O)(c1cc(C[C@H](NC(c2c(Cl)c(CCN(C(c(cc3)cc4c3cco4)=O)C5)c5cc2Cl)=O)C([O-])=O)ccc1)=O.[Na+]
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>3 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Lifitegrast (SAR 1118) sodium is a potent integrin antagonist.
In vitro activity:
Herein, this study presents a first account of the structural dynamics which characterizes the inhibitory effect of a novel LFA-1 antagonist, Lifitegrast (SAR1118), upon binding to the I-domain allosteric site (IDAS) using molecular dynamics simulation. Findings from this study revealed that the inhibitor stabilized the closed conformation and reversed the open conformation to a low ICAM-affinity state (closed) as evidenced by the upward movement of the α7 helix and corresponding transitions at the active site.
Reference: Comput Biol Chem. 2018 Apr;73:49-56. https://pubmed.ncbi.nlm.nih.gov/29427909/
In vivo activity:
To determine if lifitegrast inhibits corneal inflammation induced by tobramycin-killed S. aureus, mice were given 1% lifitegrast topically at 15, 3, and 1 h before abrading the cornea and inducing inflammation with tobramycin-killed S. aureus. As shown in Fig. 3B, neutrophil numbers, corneal haze, and corneal thickness were significantly lower in lifitegrast compared with control mice, indicating that lifitegrast also inhibits corneal inflammation induced by killed S. aureus.
Reference: J Ocul Pharmacol Ther. 2013 May;29(4):395-402. https://pubmed.ncbi.nlm.nih.gov/23215542/
Preparing Stock Solutions
The following data is based on the
product
molecular weight
637.46
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Sella R, Cohen-Tayar Y, Noguchi T, Finburgh EN, Lian RR, Abbas AA, Hakim DF, Bu JJ, Zhao J, Shaw P, Bahar I, Afshari NA. The Effect of Anti-Inflammatory Topical Ophthalmic Treatments on In Vitro Corneal Epithelial Cells. Transl Vis Sci Technol. 2022 Sep 1;11(9):16. doi: 10.1167/tvst.11.9.16. PMID: 36129699; PMCID: PMC9513739.
2. Abdullahi M, Olotu FA, Soliman ME. Allosteric inhibition abrogates dysregulated LFA-1 activation: Structural insight into mechanisms of diminished immunologic disease. Comput Biol Chem. 2018 Apr;73:49-56. doi: 10.1016/j.compbiolchem.2018.02.002. Epub 2018 Feb 5. PMID: 29427909.
3. Sun Y, Zhang R, Gadek TR, O'Neill CA, Pearlman E. Corneal inflammation is inhibited by the LFA-1 antagonist, lifitegrast (SAR 1118). J Ocul Pharmacol Ther. 2013 May;29(4):395-402. doi: 10.1089/jop.2012.0102. Epub 2012 Dec 5. PMID: 23215542; PMCID: PMC3643258.
4. Rao VR, Prescott E, Shelke NB, Trivedi R, Thomas P, Struble C, Gadek T, O'Neill CA, Kompella UB. Delivery of SAR 1118 to the retina via ophthalmic drops and its effectiveness in a rat streptozotocin (STZ) model of diabetic retinopathy (DR). Invest Ophthalmol Vis Sci. 2010 Oct;51(10):5198-204. doi: 10.1167/iovs.09-5144. Epub 2010 May 5. PMID: 20445119; PMCID: PMC3066602.
In vitro protocol:
1. Sella R, Cohen-Tayar Y, Noguchi T, Finburgh EN, Lian RR, Abbas AA, Hakim DF, Bu JJ, Zhao J, Shaw P, Bahar I, Afshari NA. The Effect of Anti-Inflammatory Topical Ophthalmic Treatments on In Vitro Corneal Epithelial Cells. Transl Vis Sci Technol. 2022 Sep 1;11(9):16. doi: 10.1167/tvst.11.9.16. PMID: 36129699; PMCID: PMC9513739.
2. Abdullahi M, Olotu FA, Soliman ME. Allosteric inhibition abrogates dysregulated LFA-1 activation: Structural insight into mechanisms of diminished immunologic disease. Comput Biol Chem. 2018 Apr;73:49-56. doi: 10.1016/j.compbiolchem.2018.02.002. Epub 2018 Feb 5. PMID: 29427909.
In vivo protocol:
1. Sun Y, Zhang R, Gadek TR, O'Neill CA, Pearlman E. Corneal inflammation is inhibited by the LFA-1 antagonist, lifitegrast (SAR 1118). J Ocul Pharmacol Ther. 2013 May;29(4):395-402. doi: 10.1089/jop.2012.0102. Epub 2012 Dec 5. PMID: 23215542; PMCID: PMC3643258.
2. Rao VR, Prescott E, Shelke NB, Trivedi R, Thomas P, Struble C, Gadek T, O'Neill CA, Kompella UB. Delivery of SAR 1118 to the retina via ophthalmic drops and its effectiveness in a rat streptozotocin (STZ) model of diabetic retinopathy (DR). Invest Ophthalmol Vis Sci. 2010 Oct;51(10):5198-204. doi: 10.1167/iovs.09-5144. Epub 2010 May 5. PMID: 20445119; PMCID: PMC3066602.
1: Haber SL, Benson V, Buckway CJ, Gonzales JM, Romanet D, Scholes B. Lifitegrast: a novel drug for patients with dry eye disease. Ther Adv Ophthalmol. 2019 Aug 22;11:2515841419870366. doi: 10.1177/2515841419870366. eCollection 2019 Jan-Dec. Review. PubMed PMID: 31489402; PubMed Central PMCID: PMC6710705.
2: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from http://www.ncbi.nlm.nih.gov/books/NBK500874/ PubMed PMID: 29999933.
3: Lollett IV, Galor A. Dry eye syndrome: developments and lifitegrast in perspective. Clin Ophthalmol. 2018 Jan 15;12:125-139. doi: 10.2147/OPTH.S126668. eCollection 2018. Review. PubMed PMID: 29391773; PubMed Central PMCID: PMC5774475.
4: Donnenfeld ED, Perry HD, Nattis AS, Rosenberg ED. Lifitegrast for the treatment of dry eye disease in adults. Expert Opin Pharmacother. 2017 Oct;18(14):1517-1524. doi: 10.1080/14656566.2017.1372748. Epub 2017 Sep 4. Review. PubMed PMID: 28841079.
5: Godin MR, Gupta PK. Lifitegrast ophthalmic solution in the treatment of signs and symptoms of dry eye disease: design, development, and place in therapy. Clin Ophthalmol. 2017 May 22;11:951-957. doi: 10.2147/OPTH.S117188. eCollection 2017. Review. PubMed PMID: 28579745; PubMed Central PMCID: PMC5449132.
6: Hussar DA, Cheeseman RS 2nd. Lifitegrast, Bezlotoxumab, and Sugammadex sodium. J Am Pharm Assoc (2003). 2017 Mar - Apr;57(2):284-287. doi: 10.1016/j.japh.2017.02.004. Review. PubMed PMID: 28285777.
7: Keating GM. Lifitegrast Ophthalmic Solution 5%: A Review in Dry Eye Disease. Drugs. 2017 Feb;77(2):201-208. doi: 10.1007/s40265-016-0681-1. Review. PubMed PMID: 28058622.
8: Semba CP, Gadek TR. Development of lifitegrast: a novel T-cell inhibitor for the treatment of dry eye disease. Clin Ophthalmol. 2016 Jun 10;10:1083-94. doi: 10.2147/OPTH.S110557. eCollection 2016. Review. PubMed PMID: 27354762; PubMed Central PMCID: PMC4910612.
9: Perez VL, Pflugfelder SC, Zhang S, Shojaei A, Haque R. Lifitegrast, a Novel Integrin Antagonist for Treatment of Dry Eye Disease. Ocul Surf. 2016 Apr;14(2):207-15. doi: 10.1016/j.jtos.2016.01.001. Epub 2016 Jan 22. Review. PubMed PMID: 26807723.
