title: 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: 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.
authors.affiliation: Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing, China.
authors.lastname: He Xiao
authors.forename: Jian-Nan
authors.initials: JN
authors.lastname: Feng
authors.forename: Zu-Yin
authors.initials: ZY
authors.lastname: Yu
authors.lastname: Lei Zhang
authors.lastname: Ming Yu
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: He
authors.lastname: Song Li
authors.forename: Bei-Fen
authors.initials: BF
authors.lastname: Shen
authors.lastname: Yan Li
mesh_terms: D000465:Algorithms; D015704:CD4 Antigens / Q000187:drug effects*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D017076:Computer-Aided Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D008954:Models, Biological; D008958:Models, Molecular; D011725:Pyridines / Q000494:pharmacology*; D012397:Rosette Formation; D058924:Thienopyridines; D013876:Thiophenes / Q000494:pharmacology*
chemical_list: D015704:CD4 Antigens; D007376:Interleukin-2; C525029:N-((pyridine-4-yl)methylene)thiophene-2-carbohydrazide; D011725:Pyridines; D058924:Thienopyridines; D013876:Thiophenes