| Autor: |
Kelly TA; Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877, USA. tkelly@rdg.boehringer-ingelheim.com, Jeanfavre DD, McNeil DW, Woska JR Jr, Reilly PL, Mainolfi EA, Kishimoto KM, Nabozny GH, Zinter R, Bormann BJ, Rothlein R |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 1999 Nov 15; Vol. 163 (10), pp. 5173-7. |
| Abstrakt: |
LFA-1 (CD18,CD11a) is a cell-adhesion molecule that mediates critical immunological processes. In this paper we report the discovery and characterization of (R)-5-(4-bromobenzyl)-3-(3, 5-dichlorophenyl)-1,5-dimethylimidazolidine-2,4-dione (BIRT 377), an orally bioavailable small molecule that interacts specifically with LFA-1 via noncovalent binding to the CD11a chain and prevents LFA-1 from binding to its ligand, ICAM-1. BIRT 377 inhibits lymphocyte activity both in vitro and in vivo, in functional assays that require LFA-1-mediated cell adhesion. These results demonstrate that LFA-1-mediated leukocyte adhesion can be antagonized with noncharged, low m.w. molecules and suggest that the potential therapeutic value of adhesion inhibitors can be attained with a small, orally bioavailable compound. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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