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BioAssay: AID 258919

Inhibition of leukotriene D4 at 100 nM

Serotonin 5-HT(2) receptor agonists have been identified as a potential new class of agents for the treatment of ocular hypertension and glaucoma. The initially reported tryptamine analogues displayed either poor solution stability, potent central nervous system activity, or both of these undesirable characteristics and were unacceptable for clinical evaluation. A series of more ..
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 Tested Compounds
 Tested Compounds
All(1)
 
 
Unspecified(1)
 
 
 Tested Substances
 Tested Substances
All(1)
 
 
Unspecified(1)
 
 
 Related BioAssays
 Related BioAssays
AID: 258919
Data Source: ChEMBL (329449)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-24
Modify Date: 2013-11-18

Data Table ( Complete ):           All
Target
Sequence: RecName: Full=Cysteinyl leukotriene receptor 1; Short=CysLTR1; AltName: Full=Cysteinyl leukotriene D4 receptor; Short=LTD4 receptor; AltName: Full=G-protein coupled receptor HG55; AltName: Full=HMTMF81
Description ..   
Protein Family: Serpentine type 7TM GPCR chemoreceptor Srx
Comment ..   

Gene:CYSLTR1     Related Protein 3D Structures     More BioActivity Data..
Tested Compound:
Description:
Title: 1-((S)-2-aminopropyl)-1H-indazol-6-ol: a potent peripherally acting 5-HT2 receptor agonist with ocular hypotensive activity.

Abstract: Serotonin 5-HT(2) receptor agonists have been identified as a potential new class of agents for the treatment of ocular hypertension and glaucoma. The initially reported tryptamine analogues displayed either poor solution stability, potent central nervous system activity, or both of these undesirable characteristics and were unacceptable for clinical evaluation. A series of 1-(2-aminopropyl)-1H-indazole analogues was synthesized and evaluated for their suitability for consideration as clinical candidates. 1-((S)-2-Aminopropyl)-1H-indazol-6-ol (9) was identified as a peripherally acting potent 5-HT(2) receptor agonist (EC(50) = 42.7 nM, E(max) = 89%) with high selectivity for the 5-HT(2) receptors relative to other serotonergic receptor subtypes and other families of receptors and has significantly greater solution stability than alpha-methyl-5-hydroxytryptamine. Additionally, 9 potently lowers intraocular pressure in conscious ocular hypertensive monkeys (-13 mmHg, 33%); this reduction appears to be through a local rather than a centrally mediated effect. Compound 9 appears to be an excellent 5-HT(2) receptor agonist for conducting further studies directed toward a clinical proof-of-concept study for this class of ocular hypotensive agents.
(PMID: 16392816)
Categorized Comment
ChEMBL Assay Type: Binding

ChEMBL Assay Data Source: Scientific Literature

ChEMBL Target ID: 179

ChEMBL Target Type: Target is a single protein chain

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)
Classification
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