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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 Medicinal Chemistry Letters 3(3): 203-206

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.


PMID: 24900456

DOI: 10.1021/ml2002482

Other references

Anonymous, 1952: International Congress on Lighting; 26-30 Sept 51. Concours Medical 74(8): 685-90 Contd

Mizandrontsev I.B.; Mizandrontseva K.N., 2002: Carbonates in Lake Baikal. Pages 228-229 2002

Reggianini, O., 1950: Contribution to the study of enzymes hydrolyzing chondroitinsulfuric acid. Bollettino Dell'istituto Sieroterapico Milanese 29(11-12): 456-460

Bremer, M., 2012: Radical prostatectomy versus observation for localized prostate cancer. Strahlentherapie und Onkologie 188(12): 1159-1160

Lepine, P.; Atanasiu, P., 1956: Antigenic and vaccinating power of Newcastle virus inactivated by beta-propiolactone. Annales de L'institut Pasteur 91(1): 100-102

Rio, M.C.S.atolin; Castro, M.M.; Kinoshita, L.S., 2002: Distribution and anatomical characterization on the foliar colleters of Prestonia coalita Woodson. A structural study on the foliar colleters of Prestonia coalita (Vell.) Woodson was conducted in order to establish their number and positions, to describe their structure, to determine in which stage of leaf development secretion starts and to co...

Cox, S.Natasha., 2015: Intracellular signaling of CTLs. Extracellular signals are transmitted to intracellular targets thanks to a complex network of interacting proteins that regulate a large number of cellular processes. The signaling mechanisms that occur in CTLs are initiated by T cell receptors (T...

Gauthier, Geraldine F., 1967: On the localization of sarcotubular ATPase activity in mammalian skeletal muscle. ATPase activity of the sarcoplasmic reticulum was demonstrated at the level of the light microscope. Although this membrane system is usually viewed as ultrastructural in its dimensions, it was possible to identify sarcotubular enzymic activity in...

Bottimer, L.J., 1926: Notes on some Lepidoptera from eastern Texas. Rearing and host records, with notes on habits and parasites, of. 40 species are reported, including CHAETOCAMPA Busck (p. 804) (Cosmopterygidae), for C. crotonella* (p. 804), reared from leaf galls and seed of Croton engelmannii. Gelechiidae: Iso...

Isobe, M., 2014: 111th Scientific Meeting of the Japanese Society of Internal Medicine: Symposium: 2. Perspective of treatment in the vascular lesion of various organs: 1) Current diagnosis and therapy of Takayasu arteritis. Nihon Naika Gakkai Zasshi. Journal of the Japanese Society of Internal Medicine 103(9): 2131-2136