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
He Xiao*,
Jian-Nan Feng,
Zu-Yin Yu,
Lei Zhang,
Ming Yu,
Xin-Hua He,
Song Li,
Bei-Fen Shen,
and
Yan Li
Institution of Beijing basical medical sciences
* To whom correspondence should be addressed. E-mail: yinher2001{at}yahoo.com.
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Abstract |
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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 XXXX:xx-xx)
