Bookmark and Share
BioAssay: AID 632621

Inhibition of human B-lymphoblastoid cell microsomal CYP2C9 (Cys) assessed as Tolbutamide hydroxylation preincubated for 5 mins with substrate

A novel naphthylmethylimidazole derivative 1 and its related compounds were identified as 17,20-lyase inhibitors. Based on the structure-activity relationship around the naphthalene scaffold and the results of a docking study of 1a in the homology model of 17,20-lyase, the 6,7-dihydro-5H-pyrrolo[1,2-c]imidazole derivative (+)-3c was synthesized and identified as a potent and highly selective more ..
_
   
 Tested Compounds
 Tested Compounds
All(1)
 
 
Unspecified(1)
 
 
 Tested Substances
 Tested Substances
All(1)
 
 
Unspecified(1)
 
 
 Related BioAssays
 Related BioAssays
AID: 632621
Data Source: ChEMBL (790069)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-09-09
Modify Date: 2014-05-24

Data Table ( Complete ):           All
Target
Sequence: RecName: Full=Cytochrome P450 2C9; AltName: Full=(R)-limonene 6-monooxygenase; AltName: Full=(S)-limonene 6-monooxygenase; AltName: Full=(S)-limonene 7-monooxygenase; AltName: Full=CYPIIC9; AltName: Full=Cytochrome P-450MP; AltName: Full=Cytochrome P450 MP-4; AltName: Full=Cytochrome P450 MP-8; AltName: Full=Cytochrome P450 PB-1; AltName: Full=S-mephenytoin 4-hydroxylase
Description ..   
Protein Family: Cytochrome P450
Comment ..   

Gene:CYP2C9     Related Protein 3D Structures     More BioActivity Data..
Tested Compound:
Description:
Title: Discovery of orteronel (TAK-700), a naphthylmethylimidazole derivative, as a highly selective 17,20-lyase inhibitor with potential utility in the treatment of prostate cancer.

Abstract: A novel naphthylmethylimidazole derivative 1 and its related compounds were identified as 17,20-lyase inhibitors. Based on the structure-activity relationship around the naphthalene scaffold and the results of a docking study of 1a in the homology model of 17,20-lyase, the 6,7-dihydro-5H-pyrrolo[1,2-c]imidazole derivative (+)-3c was synthesized and identified as a potent and highly selective 17,20-lyase inhibitor. Biological evaluation of (+)-3c at a dose of 1mg/kg in a male monkey model revealed marked reductions in both serum testosterone and dehydroepiandrosterone concentrations. Therefore, (+)-3c (termed orteronel [TAK-700]) was selected as a candidate for clinical evaluation and is currently in phase III clinical trials for the treatment of castration-resistant prostate cancer.
(PMID: 21978946)
Categorized Comment
Assay Type: ADME

Assay Data Source: Scientific Literature

Target Type: Target is a single protein chain

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)
Classification
PageFrom: