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Discovery and Development of Potent LFA-1/ICAM-1 Antagonist SAR 1118 as an Ophthalmic Solution for Treating Dry Eye

Min Zhong1, Thomas R Gadek2, Minna Bui1

  • 1Sunesis Pharmaceuticals, Inc. , 395 Oyster Point Boulevard, Suite 400, South San Francisco, California 94080, United States.

ACS Medicinal Chemistry Letters
|June 6, 2014
PubMed

LFA-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.

Keywords:
LFA-1/ICAM-1 antagonistSAR 1118dry eyeophthalmic solutiontetrahydroisoquinoline derivative

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