PT  - JOURNAL ARTICLE
AU  - Kurt Vermeire
AU  - Thomas W. Bell
AU  - Heung-Jin Choi
AU  - Qi Jin
AU  - Meinrado F. Samala
AU  - Andrej Sodoma
AU  - Erik De Clercq
AU  - Dominique Schols
TI  - The Anti-HIV Potency of Cyclotriazadisulfonamide Analogs Is Directly Correlated with Their Ability to Down-Modulate the CD4 Receptor
AID  - 10.1124/mol.63.1.203
DP  - 2003 Jan 01
TA  - Molecular Pharmacology
PG  - 203--210
VI  - 63
IP  - 1
4099  - http://molpharm.aspetjournals.org/content/63/1/203.short
4100  - http://molpharm.aspetjournals.org/content/63/1/203.full
SO  - Mol Pharmacol2003 Jan 01; 63
AB  - 9-Benzyl-3-methylene-1,5-di-p-toluenesulfonyl-1,5,9-triazacyclododecane (CADA) has been identified as a novel antiviral lead compound with significant anti-human immunodeficiency virus and anti-human herpesvirus 7 activity. Surprisingly, this compound selectively decreased the expression of the CD4 glycoprotein, the primary receptor needed for the entry of both viruses. Herein, we describe the CD4 down-modulating and antiviral potencies of more than 25 CADA derivatives. Flow cytometric evaluation of cellular CD4 receptor expression in T cells demonstrated the specific CD4 down-modulating capacity of the CADA derivatives, with IC50 values similar to those obtained in the antiviral assays. The close correlation observed between the CD4 down-regulating and anti-HIV potencies of the CADA derivatives further points to CD4 receptor down-modulation as the primary mode of antiviral action for this group of compounds.