Synonym
SAR-1118; SAR 1118; SAR1118; Lifitegrast, brand name: Xiidra.
IUPAC/Chemical Name
(S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid
InChi Key
JFOZKMSJYSPYLN-QHCPKHFHSA-N
InChi Code
InChI=1S/C29H24Cl2N2O7S/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)/t23-/m0/s1
SMILES Code
O=C(O)[C@@H](NC(C1=C(Cl)C2=C(CN(C(C3=CC=C4C=COC4=C3)=O)CC2)C=C1Cl)=O)CC5=CC=CC(S(=O)(C)=O)=C5
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, not in water
Shelf Life
>2 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) is an integrin lymphocyte function-associated antigen-1 (LFA-1; αLβ2) antagonist which inhibits Jurkat T cell attachment to ICAM-1 with an IC50 of 2.98 nM.
In vitro activity:
The ability of SAR 1118 to inhibit Jurkat T-cell binding with recombinant human ICAM-1 and to inhibit cytokine release from human peripheral blood mononuclear cells (PBMCs) stimulated by staphylococcal enterotoxin B was measured. SAR 1118 demonstrated concentration-dependent inhibition of Jurkat T-cell attachment, inhibition of lymphocyte activation, and release of inflammatory cytokines, particularly the Th1, Th2, and Th17 T-cell cytokines IFN-γ, IL-2, and IL-17F, respectively.
Reference: Invest Ophthalmol Vis Sci. 2011 May 16;52(6):3174-80. https://iovs.arvojournals.org/article.aspx?articleid=2165671
In vivo activity:
10 dogs diagnosed with idiopathic KCS (keratoconjunctivitis sicca) were treated with SAR 1118 1% topical ophthalmic solution three times daily for 12 weeks. Schirmer's tear test (STT) was used to measure tear production. Mean STT values increased from 3.4 mm during week 1 to 5.8 mm at week 12 (P < 0.025). No SAR 1118-related adverse events were observed. SAR 1118 appears to be an effective anti-inflammatory treatment for KCS.
Reference: Invest Ophthalmol Vis Sci. 2011 May 16;52(6):3174-80. https://iovs.arvojournals.org/article.aspx?articleid=2165671
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
30.0 |
15.24 |
| DMF |
30.0 |
15.24 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
615.48
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. Murphy CJ, Bentley E, Miller PE, McIntyre K, Leatherberry G, Dubielzig R, Giuliano E, Moore CP, Phillips TE, Smith PB, Prescott E, Miller JM, Thomas P, Scagliotti R, Esson D, Gadek T, O'Neill CA. The pharmacologic assessment of a novel lymphocyte function-associated antigen-1 antagonist (SAR 1118) for the treatment of keratoconjunctivitis sicca in dogs. Invest Ophthalmol Vis Sci. 2011 May 16;52(6):3174-80. doi: 10.1167/iovs.09-5078. PMID: 21330663.
In vitro protocol:
1. Murphy CJ, Bentley E, Miller PE, McIntyre K, Leatherberry G, Dubielzig R, Giuliano E, Moore CP, Phillips TE, Smith PB, Prescott E, Miller JM, Thomas P, Scagliotti R, Esson D, Gadek T, O'Neill CA. The pharmacologic assessment of a novel lymphocyte function-associated antigen-1 antagonist (SAR 1118) for the treatment of keratoconjunctivitis sicca in dogs. Invest Ophthalmol Vis Sci. 2011 May 16;52(6):3174-80. doi: 10.1167/iovs.09-5078. PMID: 21330663.
In vivo protocol:
1. Murphy CJ, Bentley E, Miller PE, McIntyre K, Leatherberry G, Dubielzig R, Giuliano E, Moore CP, Phillips TE, Smith PB, Prescott E, Miller JM, Thomas P, Scagliotti R, Esson D, Gadek T, O'Neill CA. The pharmacologic assessment of a novel lymphocyte function-associated antigen-1 antagonist (SAR 1118) for the treatment of keratoconjunctivitis sicca in dogs. Invest Ophthalmol Vis Sci. 2011 May 16;52(6):3174-80. doi: 10.1167/iovs.09-5078. PMID: 21330663.
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.
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