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BioAssay: AID 427793

Inhibition of HIV1 (isolate YU2) envelope glycoprotein 120-mediated membrane fusion between virus-transfected african green monkey COS cells and human TZM-bl cells by luciferase-based cell-cell fusion assay in absence of IC9564

Betulinic acid (BA) derivatives can inhibit human immunodeficiency virus type 1 (HIV-1) entry or maturation depending on side chain modifications. While BA derivatives with antimaturation activity have attracted considerable interest, the anti-HIV-1 profile and molecular mechanism of BA derivatives with anti-HIV-1 entry activity (termed BA entry inhibitors) have not been well defined. In this more ..
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 Tested Compounds
 Tested Compounds
All(2)
 
 
Unspecified(2)
 
 
 Tested Substances
 Tested Substances
All(2)
 
 
Unspecified(2)
 
 
 Related BioAssays
 Related BioAssays
AID: 427793
Data Source: ChEMBL (579137)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-26
Modify Date: 2013-11-16

Data Table ( Complete ):           All
Target
Sequence: RecName: Full=Envelope glycoprotein gp160; AltName: Full=Env polyprotein; Contains: RecName: Full=Surface protein gp120; Short=SU; AltName: Full=Glycoprotein 120; Short=gp120; Contains: RecName: Full=Transmembrane protein gp41; Short=TM; AltName: Full=Glycoprotein 41; Short=gp41; Flags: Precursor
Description ..   
Protein Family: Envelope glycoprotein GP120
Comment ..   

Related Protein 3D Structures     More BioActivity Data..
Tested Compounds:
Description:
Title: Betulinic acid derivatives that target gp120 and inhibit multiple genetic subtypes of human immunodeficiency virus type 1.

Abstract: Betulinic acid (BA) derivatives can inhibit human immunodeficiency virus type 1 (HIV-1) entry or maturation depending on side chain modifications. While BA derivatives with antimaturation activity have attracted considerable interest, the anti-HIV-1 profile and molecular mechanism of BA derivatives with anti-HIV-1 entry activity (termed BA entry inhibitors) have not been well defined. In this study, we have found that two BA entry inhibitors, IC9564 and A43D, exhibited a broad spectrum of anti-HIV-1 activity. Both compounds inhibited multiple strains of HIV-1 from clades A, B, and C at submicromolar concentrations. Clade C viruses were more sensitive to the compounds than clade A and B viruses. Interestingly, IC9564 at subinhibitory concentrations could alter the antifusion activities of other entry inhibitors. IC9564 was especially potent in increasing the sensitivity of HIV-1 YU2 Env-mediated membrane fusion to the CCR5 inhibitor TAK-779. Results from this study suggest that the V3 loop of gp120 is a critical determinant for the anti-HIV-1 activity of IC9564. IC9564 escape viruses contained mutations near the tip of the V3 loop. Moreover, IC9564 could compete with the binding of V3 monoclonal antibodies 447-52D and 39F. IC9564 also competed with the binding of gp120/CD4 complexes to chemokine receptors. In summary, these results suggest that BA entry inhibitors can potently inhibit a broad spectrum of primary HIV-1 isolates by targeting the V3 loop of gp120.
(PMID: 17954689)
Categorized Comment
ChEMBL Assay Type: Binding

ChEMBL Assay Data Source: Scientific Literature

ChEMBL Target ID: 102457

ChEMBL Target Type: Target is a single protein chain

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1IC50 activity commentIC50 activity commentString
2IC50 standard flagIC50 standard flagInteger
3IC50 qualifierIC50 qualifierString
4IC50 published valueIC50 published valueFloatng/ml
5IC50 standard valueIC50 standard valueFloatug.mL-1

Data Table (Concise)
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