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BioAssay: AID 776500

Antagonist activity at CCR5 (unknown origin) expressed in MOLT4 cells transfected with Gqi5 assessed as inhibition of RANTES-induced calcium ion mobilization after 15 mins by microplate reader method

Accumulating evidence has shown multiple roles that chemokine receptor CCR5 may play to promote the progression of several types of cancer. The mechanism of such promotion is believed to involve chronic inflammation that creates a microenvironment which enhances tumor survival. Therefore, blocking CCR5 function with an antagonist may provide a novel treatment of cancers such as prostate cancer. more ..
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 Tested Compounds
 Tested Compounds
All(24)
 
 
Active(6)
 
 
Unspecified(18)
 
 
 Tested Substances
 Tested Substances
All(24)
 
 
Active(6)
 
 
Unspecified(18)
 
 
AID: 776500
Data Source: ChEMBL (986898)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2014-05-03
Modify Date: 2014-08-25

Data Table ( Complete ):           View Active Data    View All Data
Target
Sequence: RecName: Full=C-C chemokine receptor type 5; Short=C-C CKR-5; Short=CC-CKR-5; Short=CCR-5; Short=CCR5; AltName: Full=CHEMR13; AltName: Full=HIV-1 fusion coreceptor; AltName: CD_antigen=CD195
Description ..   
Comment ..   

Gene:CCR5     Conserved Domain     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: 6
Description:
Title: Design, syntheses, and characterization of pharmacophore based chemokine receptor CCR5 antagonists as anti prostate cancer agents.

Abstract: Accumulating evidence has shown multiple roles that chemokine receptor CCR5 may play to promote the progression of several types of cancer. The mechanism of such promotion is believed to involve chronic inflammation that creates a microenvironment which enhances tumor survival. Therefore, blocking CCR5 function with an antagonist may provide a novel treatment of cancers such as prostate cancer. Currently, several CCR5 antagonists are available, but all have been optimized for their inhibitory activity on HIV-1 cellular membrane invasion process rather than inhibition on cytoplasmic signaling pathways. Thus, there is need to develop CCR5 antagonists focusing on blockage of CCR5 downstream signaling and inhibition of CCR5 related prostate cancer proliferation and progression. In this report, a pharmacophore analysis was conducted based on docking studies of several known CCR5 antagonists in a CCR5 homology model. A unique structural skeleton for CCR5 antagonist was constructed and functionalized, resulting in a new series of small molecules to be synthesized and characterized. A combination of CCR5 calcium flux inhibition, anti prostate cancer cell proliferation, basal cytotoxicity, and in vivo animal model studies were applied to screen the newly synthesized compounds. Results from this study provided a potential lead compound for future CCR5 antagonist development focusing on prostate cancer therapy.
(PMID: 24095757)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.
Categorized Comment - additional comments and annotations
From BioAssay Depositor:
Assay Type: Binding
Target Type: Target is a single protein chain
Assay Data Source: Scientific Literature
BAO: Assay Format: cell-based format
Assay Test Type: In vitro
Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1IC50*IC50 PubChem standard valueFloatμM
3BEIBinding Efficiency Index(nM)Float
2SEISurface Efficiency Index(nM)Float
4LELigand EfficiencyFloat
5LLELipophilic Ligand EfficiencyFloat
6IC50 activity commentIC50 activity commentString
7IC50 standard flagIC50 standard flagInteger
8IC50 qualifierIC50 qualifierString
9IC50 published valueIC50 published valueFloatμM
10IC50 standard valueIC50 standard valueFloatnM
11IC50 data validityIC50 data validityString
12Inhibition activity commentInhibition activity commentString
13Inhibition standard flagInhibition standard flagInteger
14Inhibition qualifierInhibition qualifierString
15Inhibition published valueInhibition published valueFloat
16Inhibition standard valueInhibition standard valueFloat
17Inhibition data validityInhibition data validityString

* Activity Concentration.

Data Table (Concise)
Data Table ( Complete ):     View Active Data    View All Data
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