Title: Improving potencies and properties of CD4 down-modulating CADA analogs
Authors: Bell, Thomas W ×
Demillo, Violeta G
Schols, Dominique
Vermeire, Kurt #
Issue Date: Jan-2012
Publisher: Informa Healthcare
Series Title: Expert Opinion on Drug Discovery vol:7 issue:1 pages:39-48
Abstract: Introduction: CADA is a synthetic small molecule that inhibits HIV replication in cell cultures through down-modulating cell surface CD4 by inhibiting cotranslational translocation of nascent CD4 across the ER membrane in a signal sequence-specific manner. Analogs have been prepared mainly to increase potency and investigate the mechanism of action. Areas covered: This article reviews progress on discovery of more potent CADA analogs, including symmetrical and unsymmetrical compounds, as well as fluorescent derivatives. The article also discusses some properties of CADA and a more potent analog (KKD023) that are relevant to drug development, including aqueous solubility, permeability, metabolism and oral bioavailability. Expert opinion: Further studies on CADA analogs should focus on improving both potency and drug-like properties, and on elucidating the detailed mechanism of action. Solubility and permeability may be improved by reducing molecular weight, decreasing molecular flexibility and symmetry, or by a prodrug approach inducing active transport. Identifying the molecular mechanism of CD4 down-modulation may aid in assessing potential side effects of such immunomodulatory/anti-HIV drugs, and it could potentially lead to a general approach to designing drugs for specifically down-modulating other cell-surface proteins.
ISSN: 1746-0441
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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