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BioAssay: AID 637432

Cmax in Sprague-Dawley rat at 10 mg/kg after 0.5 to 8 hrs by HPLC analysis

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(2)
 
 
Active(2)
 
 
 Tested Substances
 Tested Substances
All(2)
 
 
Active(2)
 
 
 Related BioAssays
 Related BioAssays
AID: 637432
Data Source: ChEMBL (794880)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-09-09
Modify Date: 2014-05-25

Data Table ( Complete ):           Active    All
BioActive Compounds: 2
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
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: 50597
Target Type: ORGANISM
Pref Name: Rattus norvegicus
Organism: Rattus norvegicus
Tax ID: 10116
Confidence: Target assigned is non-molecular
Relationship Type: Non-molecular target assigned
Categorized Comment
Assay Type: ADME

Assay Data Source: Scientific Literature

Assay Test Type: In vivo

BAO: Assay Format: organism-based format

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Cmax activity commentCmax activity commentString
2Cmax standard flagCmax standard flagInteger
3Cmax qualifierCmax qualifierString
4Cmax published valueCmax published valueFloatμM
5Cmax standard valueCmax standard valueFloatnM

Data Table (Concise)
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