title: Discovery of small molecular inhibitors targeting HIV-1 gp120-CD4 interaction drived from BMS-378806.
abstract: The HIV-1 entry into host cells is a complex, multi-factors involved, and multi-step process. Especially, the attachment of HIV-1 envelope glycoprotein gp120 to the host cell receptor CD4 is the first key step during entry process, representing a promising antiviral therapeutic target. Among the HIV-1 attachment inhibitors blocking the interaction between gp120 and CD4 cells, BMS-378806 and NBD-556 are two representative small molecular chemical entities. Particularly, BMS-378806 and its derivatives are newly identified class of orally bioavailable HIV-1 inhibitors that interfere gp120-CD4 interaction. In this review, we focused on describing the structure-activity relationships (SARs), structural modifications, in vitro or even in vivo pharmacodynamics and pharmacokinetics of BMS-378806 and its analogues as HIV-1 gp120 attachment inhibitors. In addition, the brief SARs, structural modifications of NBD-556 and its derivatives targeting the "Phe-43 cavity" as CD4 mimics were also described.
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, 250012, Jinan, Shandong, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, 250012, Jinan, Shandong, PR China.
authors.forename: Boshi
authors.initials: B
authors.lastname: Huang
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, 250012, Jinan, Shandong, PR China. Electronic address: zhanpeng1982@163.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhan
authors.affiliation: Rega Institute for Medical Research, K.U. Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, 250012, Jinan, Shandong, PR China. Electronic address: xinyongllab@163.com.
authors.forename: Xinyong
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000737:chemistry / Q000378:metabolism*; D055808:Drug Discovery; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C477855:BMS-378806; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D010879:Piperazines; D054852:Small Molecule Libraries
keywords: AIDS; Attachment inhibitors; BMS-378806; Drug design; HIV-1; NBD-556; gp120