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BioAssay: AID 637388

Ratio of rosiglitazone ED50 to compound ED50 for po dosed diabetic KK-Ay mouse model

A novel series of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives were synthesized and (S)-2-[(2E,4E)-hexadienoyl]-7-(2-{5-methyl-2-[(1E)-5-methylhexen-1-yl]oxazol-4-yl}ethoxy)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (14i) was identified as a potent human peroxisome proliferator-activated receptor gamma (PPARgamma) selective agonist (EC(50)=0.03 muM) and human 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: 637388
Data Source: ChEMBL (794836)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-09-09
Modify Date: 2014-05-25

Data Table ( Complete ):           View All Data
Tested Compound:
Description:
Title: Novel (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids: peroxisome proliferator-activated receptor gamma selective agonists with protein-tyrosine phosphatase 1B inhibition.

Abstract: A novel series of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives were synthesized and (S)-2-[(2E,4E)-hexadienoyl]-7-(2-{5-methyl-2-[(1E)-5-methylhexen-1-yl]oxazol-4-yl}ethoxy)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (14i) was identified as a potent human peroxisome proliferator-activated receptor gamma (PPARgamma) selective agonist (EC(50)=0.03 muM) and human protein-tyrosine phosphatase 1B (PTP-1B) inhibitor (IC(50)=1.18 muM). C(max) after oral administration of 14i at 10mg/kg was 2.2 mug/ml (4.5 muM) in male SD rats. Repeated administration of 14i and rosiglitazone for 14 days dose-dependently decreased plasma glucose levels, ED(50)=4.3 and 23 mg/kg/day, respectively, in male KK-A(y) mice. In female SD rats, repeated administration of 14i at 12.5-100mg/kg/day for 28 days had no effect on the hematocrit value (Ht) and red blood cell count (RBC), while rosiglitazone significantly decreased them from 25mg/kg/day. In conclusion, 14i showed about a fivefold stronger hypoglycemic effect and fourfold or more weaker hemodilution effect than rosiglitazone, indicating that 14i is 20-fold or more safer than rosiglitazone. Compound 14i is a promising candidate for an efficacious and safe anti-diabetic drug targeting PPARgamma and PTP-1B.
(PMID: 22197396)
Comment
Putative Target:

ChEMBL Target ID: 50594
Target Type: ORGANISM
Pref Name: Mus musculus
Organism: Mus musculus
Tax ID: 10090
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
1Ratio ED50 activity commentRatio ED50 activity commentString
2Ratio ED50 standard flagRatio ED50 standard flagInteger
3Ratio ED50 qualifierRatio ED50 qualifierString
4Ratio ED50 published valueRatio ED50 published valueFloat
5Ratio ED50 standard valueRatio ED50 standard valueFloat

Data Table (Concise)
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