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BioAssay: AID 537009

Displacement of [3H]AL-11 from human IRAP expressed in CHO-K1 cells after 30 mins by liquid scintillation counting in absence of 30 mM EDTA/600 uM 1,10-Phe

The insulin-regulated aminopeptidase (IRAP) localized in areas of the brain associated with memory and learning is emerging as a new promising therapeutic target for the treatment of memory dysfunctions. The angiotensin II metabolite angiotensin IV (Ang IV, Val(1)-Tyr(2)-Ile(3)-His(4)-Pro(5)-Phe(6)) binds with high affinity to IRAP and inhibits this aminopeptidase (K(i) = 62.4 nM). Furthermore, more ..
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 Tested Compounds
 Tested Compounds
All(12)
 
 
Active(12)
 
 
 Tested Substances
 Tested Substances
All(12)
 
 
Active(12)
 
 
AID: 537009
Data Source: ChEMBL (684890)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2011-09-18
Modify Date: 2014-08-23

Data Table ( Complete ):           View Active Data    View All Data
Target
Sequence: RecName: Full=Leucyl-cystinyl aminopeptidase; Short=Cystinyl aminopeptidase; AltName: Full=Insulin-regulated membrane aminopeptidase; AltName: Full=Insulin-responsive aminopeptidase; Short=IRAP; AltName: Full=Oxytocinase; Short=OTase; AltName: Full=Placental leucine aminopeptidase; Short=P-LAP; Contains: RecName: Full=Leucyl-cystinyl aminopeptidase, pregnancy serum form
Description ..   
Protein Family: Peptidase M1 Aminopeptidase N family incudes tricorn interacting factor F3, Endoplasmic reticulum aminopeptidase 1 (ERAP1), Aminopeptidase Q (APQ)
Comment ..   

Gene:LNPEP     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: 12
Description:
Title: Disulfide cyclized tripeptide analogues of angiotensin IV as potent and selective inhibitors of insulin-regulated aminopeptidase (IRAP).

Abstract: The insulin-regulated aminopeptidase (IRAP) localized in areas of the brain associated with memory and learning is emerging as a new promising therapeutic target for the treatment of memory dysfunctions. The angiotensin II metabolite angiotensin IV (Ang IV, Val(1)-Tyr(2)-Ile(3)-His(4)-Pro(5)-Phe(6)) binds with high affinity to IRAP and inhibits this aminopeptidase (K(i) = 62.4 nM). Furthermore, Ang IV has been demonstrated to enhance cognition in animal models and is believed to play an important role in cognitive processes. It is herein reported that displacement of the C-terminal tripeptide His(4)-Pro(5)-Phe(6) with a phenylacetic acid functionality combined with a constrained macrocyclic system in the N-terminal affords potent IRAP inhibitors that are less peptidic in character than the hexapeptide Ang IV. Configurational analysis of three pairs of diastereomeric Ang IV analogues was performed using a combination of solution NMR spectroscopic methods, Monte Carlo conformational searches, and NAMFIS calculations. The compounds encompassing l-amino acids only (4, 8, and 12) showed significantly higher bioactivity compared to their lld-epimers (5, 9, and 13). The best inhibitors in the series, compounds 8 and 12, incorporating a 13- and 14-membered disulfide ring system, respectively, and both with a beta(3)-homotyrosine residue (beta(3)hTyr) replacing Tyr(2), exhibit K(i) values of 3.3 and 5.2 nM, respectively.
(PMID: 21047126)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.
Categorized Comment - additional comments and annotations
From BioAssay Depositor:
Assay Type: Binding
Target Type: Target is a single protein chain
Assay Data Source: Scientific Literature
BAO: Assay Format: cell-based format
Assay Cell Type: CHO-K1
Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Ki*Ki PubChem standard valueFloatμM
3BEIBinding Efficiency Index(nM)Float
2SEISurface Efficiency Index(nM)Float
4LELigand EfficiencyFloat
5LLELipophilic Ligand EfficiencyFloat
6Ki activity commentKi activity commentString
7Ki standard flagKi standard flagInteger
8Ki qualifierKi qualifierString
9Ki published valueKi published valueFloatnM
10Ki standard valueKi standard valueFloatnM

* Activity Concentration.

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