Lifitegrast
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| Non-proprietary name | Lifitegrast | |||||||||||||||||||||
| other names |
( S ) -2- [2- (Benzofuran-6-carbonyl) -5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido] -3- [3- (methylsulfonyl) phenyl] propanoic acid |
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| Molecular formula | C 29 H 24 Cl 2 N 2 O 7 S | |||||||||||||||||||||
| Brief description |
White to off-white powder |
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| Molar mass | 615.5 g · mol -1 | |||||||||||||||||||||
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | ||||||||||||||||||||||
Lifitegrast is a medicine used in the treatment of dry eye ( keratoconjunctivitis sicca ). Lifitegrast is one of the integrin antagonists and intervenes in immunological inflammatory processes that play a role in dry eye syndrome.
properties
Lifitegrast is a white to off-white powder that is soluble in water. The molecule has a chiral center.
Mechanism of action
Lifitegrast binds to the integrin leukocyte function antigen 1 (LFA-1), a protein found on the surface of T cells and other white blood cells ( leukocytes ), and prevents the binding to its ligand intercellular adhesion molecular 1 (ICAM-1 ). The T cell-mediated inflammatory reaction triggered by LFA-1 / ICAM-1 interaction is slowed down. ICAM-1 is over- expressed in the cornea and conjunctiva in dry eyes .
In -vitro studies have shown that Lifitegrast prevents the adhesion of T cells of a human cell line to ICAM-1 and suppresses the release of inflammatory cytokines in mononuclear cells of the peripheral blood . The exact mechanism of action in vivo is not known.
application areas
Lifitegrast is indicated as a 5% eye drop solution to treat the signs and symptoms of dry eye syndrome. For this application, it was approved by the FDA for the US market under the name Xiidra in July 2016 .
Admission Studies
For approval, more than 1000 patients were examined over twelve weeks in four randomized, placebo-controlled clinical studies. Endpoints were the symptoms of dry eyes , which were recorded using the Eye Dryness Score (EDS) and the Ocular Discomfort Score (ODS), and the signs of inflammation, which were determined using a specific staining method, Corneal Fluorescein Staining (CFS), and the Schirmer Tear Test (STT) were measured. In all four studies, Xiidra was shown to be effective against the symptoms of dry eyes or inflammation of the conjunctiva.
Side effects
The most common side effects reported were eye irritation, taste disturbances ( dysgeusia ) and reduced visual acuity, which occurred in 5 to 25% of the treated patients.
Commercial preparations
- Shire plc / Takeda Pharmaceutical : Xiidra (USA)
Individual evidence
- ↑ a b c d Xiidra Prescribing Information , July 2016.
- ↑ a b Biomol.de: Lifitegrast, CAS 1025967-78-5 | Cayman Chemical | Biomol.de , accessed on November 5, 2019
- ↑ Billion dollar deal from Novartis. In: bazonline.ch . May 9, 2019, accessed June 1, 2019 .