Discovery and Development of Potent LFA-1/ICAM-1 Antagonist SAR 1118 as an Ophthalmic Solution for Treating Dry Eye
2012; American Chemical Society; Volume: 3; Issue: 3 Linguagem: Inglês
10.1021/ml2002482
ISSN1948-5875
AutoresMin Zhong, Thomas R. Gadek, Minna Bui, Shen Wang, John P. Burnier, Kenneth J. Barr, Emily J. Hanan, Johan D. Oslob, Chul H. Yu, Jiang Zhu, Michelle R. Arkin, Marc Evanchik, W. Mike Flanagan, Ute Hoch, Jennifer Hyde, Saileta Prabhu, Jeffrey A. Silverman, Jasmin Wright,
Tópico(s)Corneal Surgery and Treatments
ResumoLFA-1/ICAM-1 interaction is essential in support of inflammatory and specific T-cell regulated immune responses by mediating cell adhesion, leukocyte extravasation, migration, antigen presentation, formation of immunological synapse, and augmentation of T-cell receptor signaling. The increase of ICAM-1 expression levels in conjunctival epithelial cells and acinar cells was observed in animal models and patients diagnosed with dry eye. Therefore, it has been hypothesized that small molecule LFA-1/ICAM-1 antagonists could be an effective topical treatment for dry eye. In this letter, we describe the discovery of a potent tetrahydroisoquinoline (THIQ)-derived LFA-1/ICAM-1 antagonist (SAR 1118) and its development as an ophthalmic solution for treating dry eye.
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