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

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

  • ACS Med Chem Lett. 2012 Jan 31;3(3):203-6. doi: 10.1021/ml2002482.
Min Zhong 1,  Thomas R Gadek 2,  Minna Bui 1,  Wang Shen 1,  John Burnier 2,  Kenneth J Barr 1,  Emily J Hanan 1,  Johan D Oslob 1,  Chul H Yu 1,  Jiang Zhu 1,  Michelle R Arkin 1,  Marc J Evanchik 1,  W Mike Flanagan 1,  Ute Hoch 1,  Jennifer Hyde 1,  Saileta Prabhu 1,  Jeffrey A Silverman 1,  Jasmin Wright 1
Affiliations

Affiliations

  • 1 Sunesis Pharmaceuticals, Inc. , 395 Oyster Point Boulevard, Suite 400, South San Francisco, California 94080, United States.
  • 2 SARcode Bioscience, Inc. , 1000 Marina Boulevard, Suite 250, Brisbane, California 94005, United States.
PMID: 24900456 DOI: 10.1021/ml2002482
Abstract

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 antagonist; SAR 1118; dry eye; ophthalmic solution; tetrahydroisoquinoline derivative.

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