Target Validation Information
TTD ID	T57011
Target Name	ICAM1 messenger RNA (ICAM1 mRNA)
Type of Target	Successful
Drug Potency against Target	A-286982	Drug Info	IC50 = 44 nM	[1]
Action against Disease Model	Alicaforsen	Drug Info	Immunotoxicity studies were performed in mice to elucidate the nature of effects of ISIS 2302 on mammalian immune function. ISIS 2302 (1, 5, 20, or 50 mg/kg/dose) was administered intravenously every other day for 27 days. The pro-inflammatory properties of the drug were observed at doses > or = 20 mg/kg. A dose-dependent increase in spleen weight was associated with increased absolute splenocyte and B-lymphocyte counts after the 50 mg/kg/dose regimen. The mitogenic response of B-lymphocytes to bacterial lipopolysaccharide was increased after the 20 and 50 mg/kg/doses but antibody-forming cell activities remained unchanged. Total ser uM IgG concentration was decreased after the 20 and 50 mg/kg/dose regimens but IgM titers were unchanged. Increases in IL-6, IL-12, andMCP-1 as well as NK cell activity were observed after administration of 20 and 50 mg/kg/dose. Cytotoxic T-lymphocyte activity was decreased by the 50 mg/kg/dose regimen. Other changes in immune function were not observed in ISIS 2302-dosed mice	[2]
References
REF 1	Discovery of tetrahydroisoquinoline (THIQ) derivatives as potent and orally bioavailable LFA-1/ICAM-1 antagonists. Bioorg Med Chem Lett. 2010 Sep 1;20(17):5269-73.
REF 2	Assessment of the effects of ISIS 2302, an anti-sense inhibitor of human ICAM-1, on cellular and humoral immunity in mice. J Immunotoxicol. 2006 Dec 1;3(4):199-211.

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