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BioAssay: AID 76209

Inhibitory activity of compound in guinea pig ileum tissue

In order to test the theory that high mu-activity of opioid peptides could be elicited by the presence of an amino-terminal L-Tyr residue and a Phe aromatic ring held in the proper relative spatial disposition, a novel series of hybrid retro peptides were prepared in which L-Tyr was linked to N-acyl Phe through a variety of diamine spacers. These compounds were evaluated for opioid agonist and more ..
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Active(1)
 
 
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AID: 76209
Data Source: ChEMBL (73384)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-21
Modify Date: 2014-05-18

Data Table ( Complete ):           View Active Data    View All Data
BioActive Compound: 1
Description:
Title: Minimum-structure enkephalin analogues incorporating L-tyrosine, D(or L)-phenylalanine, and a diamine spacer.

Abstract: In order to test the theory that high mu-activity of opioid peptides could be elicited by the presence of an amino-terminal L-Tyr residue and a Phe aromatic ring held in the proper relative spatial disposition, a novel series of hybrid retro peptides were prepared in which L-Tyr was linked to N-acyl Phe through a variety of diamine spacers. These compounds were evaluated for opioid agonist and antagonist activity in the guinea pig ileum (GPI) in vitro assay. Analogues containing a 1,2-ethanediamine spacer, which conferred a Tyr-Phe separation distance closest to that found in Phe3 opioid peptides, were more potent agonists than the corresponding analogues containing a 1,3-propanediamine spacer. Agonist activity was observed for both L-Phe and D-Phe analogues, consistent with the known activity for both Phe stereochemistries for certain Phe3 opioid peptide analogues. Concerning the diamine spacer, conformational constraints imposed by 4-aminopiperidine and 4-(aminomethyl)piperidine as well as the presence of a hydroxyl group eliminated activity, but the presence of gem-dimethyl substitution next to the nitrogen attached to Tyr increased activity substantially for the D-Phe derivatives. Removal of the N-acetyl group from Phe did not eliminate activity. Naloxone Ke values determined for six of the most potent analogues are indicative of predominantly mu-agonism, but the D-Phe compounds 3a and 6a (1.4-2.1 nM) appear to be more mu-selective than the L-Phe compounds 2b, 3b, 5b, and 6b (3.3-4.4 nM), even though the latter are more potent agonists. Compounds 3a and 3b, which were found to be 10 and 21 times more potent, respectively, than morphine in the GPI, are two of the most structurally simple yet potent opioid peptide analogues described to date.
(PMID: 2754695)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Putative Target:

ChEMBL Target ID: 50512
Target Type: ORGANISM
Pref Name: Cavia porcellus
Organism: Cavia porcellus
Tax ID: 10141
Confidence: Target assigned is non-molecular
Relationship Type: Non-molecular target assigned
Categorized Comment - additional comments and annotations
From ChEMBL:
Assay Type: Functional
Assay Data Source: Scientific Literature
BAO: Assay Format: organism-based format
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1IC50*IC50 PubChem standard valueFloatμM
2IC50 activity commentIC50 activity commentString
3IC50 standard flagIC50 standard flagInteger
4IC50 qualifierIC50 qualifierString
5IC50 published valueIC50 published valueFloatnM
6IC50 standard valueIC50 standard valueFloatnM

* Activity Concentration.

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