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Abstract

In this study, the authors apply a computer-based strategy to screen thousands of small-molecule, nonpeptidic organic compounds in the Available Chemicals Directory database and to select a series of potential candidates as ligands of the proposed CD4 D1 surface pocket. Then, several cell-based models are used to determine the actual biological functions of these compounds. A small molecule designated A5 (N-((pyridine-4-yl)methylene)thiophene-2-carbohydrazide) was obtained by a virtual screening followed by 3 cell-based functional assays. The results show that A5 could specifically block the CD4—major histocompatibility complex II binding in a rosetting assay, inhibit the mixed lymphocyte reaction—induced T-cell proliferation in a concentration-dependent manner, and reduce the PMA plus ionomycin—stimulated interleukin-2 secretion from peripheral blood mononuclear cells. (Journal of Biomolecular Screening 2007:800-808)

Keywords

CD4—MHC II interaction computer-aided screening novel CD4 D1 inhibitor cell-based functional assays

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A5,a New Small-Molecule Inhibitor of CD4 D1 Obtained from a Computer-Aided Screening Method,Contributes to the Inhibition of CD4 + T-cell Function

Abstract

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