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A new class of HIV-1 inhibitors and the target identification via proteomic profiling
Ge, Ying-Zi1; Zhou, Bin1; Xiao, Ruo-Xuan1; Yuan, Xiao-Jing1; Zhou, Hu1; Xu, Ye-Chun1; Wainberg, Mark A.2; Han, Ying-Shan2; Yue, Jian-Min1
2018-11
Source PublicationSCIENCE CHINA-CHEMISTRY
ISSN1674-7291
Volume61Issue:11Pages:1430-1439
AbstractAnti-HIV screening with the MT-4/MTT assay on a focused library of structurally diverse natural products has led to the discovery of a group of steroids with potent activities, which include four new ergostane-type steroids, named amotsterols A-D (1-4), together with two known analogs. Among them, the most potent amotsterol D (4) exhibited anti-HIV activity against wildtype and some clinically relevant multidrug resistant HIV-1 strains. Subsequent studies on its target identification through a proteomic approach found that compound 4 might target PKM2, a rate limiting enzyme of glycolysis, in host cells to restrict HIV replication. The docking model of compound 4 to PKM2 showed that the two hydroxyl groups of 4 form hydrogen bonds with the two parallel Y390 in each subunit of PKM2 separately, and the ring C of 4 is sandwiched between the two parallel aromatic rings of F26. The identified hit compound may have the potential to be further developed as a novel anti-HIV agent. These results demonstrated that an integrated approach, which combines new chemical structures and phenotypic screening with a proteomic approach, could not only identify novel HIV-1 inhibitors, but also elucidate the unknown targets of compound interactions in antiviral drug discovery.
Keywordergostane-type steroids anti-HIV target identification PKM2
WOS KeywordINTEGRASE INHIBITORS ; NATURAL-PRODUCTS ; STABILITY DARTS ; DRUG DISCOVERY ; TRICHILIA-CONNAROIDES ; LIMONOIDS ; STEROLS ; PKM2 ; RESISTANCE ; ACTIVATORS
SubtypeArticle
DOI10.1007/s11426-018-9283-3
Indexed BySCIE ; EI
Language英语
Funding ProjectNational Natural Science Foundation of China[21532007] ; National Natural Science Foundation of China[U1302222] ; "Personalized Medicines-Molecular Signature-based Drug Discovery and Development" Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020321] ; Canadian Institutes for Health Research (CIHR)[00000000]
WOS Research AreaChemistry
WOS SubjectChemistry, Multidisciplinary
WOS IDWOS:000450158400015
PublisherSCIENCE PRESS
EI Accession Number20182605385789
EI KeywordsHydrogen bonds ; Outsourcing
Citation statistics
Cited Times:3[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://119.78.100.183/handle/2S10ELR8/279514
Collection天然药物化学研究室_岳建民课题组
分析化学研究室_周虎课题组
Corresponding AuthorHan, Ying-Shan; Yue, Jian-Min
Affiliation1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China;
2.McGill Univ, Jewish Gen Hosp, AIDS Ctr, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada
First Author AffilicationState Key Laboratory of Drug Research
Corresponding Author AffilicationState Key Laboratory of Drug Research
Recommended Citation
GB/T 7714
Ge, Ying-Zi,Zhou, Bin,Xiao, Ruo-Xuan,et al. A new class of HIV-1 inhibitors and the target identification via proteomic profiling[J]. SCIENCE CHINA-CHEMISTRY,2018,61(11):1430-1439.
APA Ge, Ying-Zi.,Zhou, Bin.,Xiao, Ruo-Xuan.,Yuan, Xiao-Jing.,Zhou, Hu.,...&Yue, Jian-Min.(2018).A new class of HIV-1 inhibitors and the target identification via proteomic profiling.SCIENCE CHINA-CHEMISTRY,61(11),1430-1439.
MLA Ge, Ying-Zi,et al."A new class of HIV-1 inhibitors and the target identification via proteomic profiling".SCIENCE CHINA-CHEMISTRY 61.11(2018):1430-1439.
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