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BioAssay: AID 763729

Inhibition of human recombinant cathepsin S using Z-Val-Val-Arg-AMC as substrate at 50 uM preincubated for 10 mins prior to substrate addition measured after 30 mins by fluorescence spectrophotometric analysis relative to control

We disclose the discovery of a novel series of tetrahydropyrido-pyrazoles that are potent inhibitors of tumour necrosis factor-alpha (TNF-alpha), nitric oxide and cannabinoid receptor subtype 1 (CB#). We report herein the synthesis and neuropharmacological screening results of the titled compounds in two acute pain and two neuropathic pain models in rodents. Particularly the analogue more ..
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 Tested Compounds
 Tested Compounds
All(3)
 
 
Unspecified(3)
 
 
 Tested Substances
 Tested Substances
All(3)
 
 
Unspecified(3)
 
 
 Related BioAssays
 Related BioAssays
AID: 763729
Data Source: ChEMBL (975997)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2014-05-03
Modify Date: 2014-08-24

Data Table ( Complete ):           View All Data
Target
Sequence: RecName: Full=Cathepsin S; Flags: Precursor
Description ..   
Protein Family: Peptidase_C1A
Comment ..   

Gene:CTSS     Related Protein 3D Structures     More BioActivity Data..
Tested Compounds:
Description:
Title: Discovery of novel tetrahydro-pyrazolo [4,3-c] pyridines for the treatment of neuropathic pain: synthesis and neuropharmacology.

Abstract: We disclose the discovery of a novel series of tetrahydropyrido-pyrazoles that are potent inhibitors of tumour necrosis factor-alpha (TNF-alpha), nitric oxide and cannabinoid receptor subtype 1 (CB#). We report herein the synthesis and neuropharmacological screening results of the titled compounds in two acute pain and two neuropathic pain models in rodents. Particularly the analogue N-(4-bromophenyl)-3-tert-butyl-5-ethyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-1-carboxamide (8a) exhibited pronounced acute antinociceptive efficacy, also being effective in chronic constriction injury (ED## = 23.8 mg/kg) and partial sciatic nerve injury (ED## = 29.0 mg/kg) models with CB# receptor activity (IC## = 49.6 nM) and inhibitory effect on TNF-alpha (86.4% inhibition at 100 mg/kg). These results suggest the importance of the development of this lead as multi-targeted treatment strategy for neuropathic pain.
(PMID: 23807113)
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
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Inhibition activity commentInhibition activity commentString
2Inhibition standard flagInhibition standard flagInteger
3Inhibition qualifierInhibition qualifierString
4Inhibition published valueInhibition published valueFloat%
5Inhibition standard valueInhibition standard valueFloat%

Data Table (Concise)
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Classification
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