Synthetic 20 base phosphorothioate antisense oligonucleotide designed to inhibit expression of intercellular adhesion molecule-1 (ICAM-1), a key mediator of inflammation. Prepn: C. F. Bennett, C. K. Mirabelli, WO 9405333; eidem, US 5514788 (1994, 1996 both to Isis). Purifn and scale up: R. R. Deshmukh et al., Nucleosides Nucleotides Nucleic Acids 20, 567 (2001). ICAM-1 inhibition in cell culture: C. F. Bennett et al., J. Immunol. 152, 3530 (1994). Clinical pharmacokinetics: J. M. Glover et al., J. Pharmacol. Exp. Ther. 282, 1173 (1997). ELISA determn in plasma: R. Z. Yu et al., Anal. Biochem. 304, 19 (2002). Clinical evaluation in Crohn's disease: B. R. Yacyshyn et al., Gut 51, 30 (2002); in ulcerative colitis: S. J. H. van Deventer et al., ibid. 53, 1646 (2004). Review of toxicology: S. P. Henry et al., Toxicol. Pathol. 27, 95-100 (1999); A. A. Levin, Biochim. Biophys. Acta 1489, 69-84 (1999); of pharmacology and clinical development: W. R. Shanahan, Jr., Expert Opin. Invest. Drugs 8, 1417-1429 (1999); C. F. Barish, Expert Opin. Biol. Ther. 5, 1387-1391 (2005).
Anti-inflammatory.
Anti-inflammatory (Biological Response Modifier); Anti-inflammatory (Gastrointestinal)