Bookmark and Share
BioAssay: AID 601497

Inhibition of catalytic activity of recombinant human IRAP transfected in human HEK-293 cells assessed as clevage of substrate L-leucine-p-nitroanilide to L-leucine and p-nitroaniline measured every 5 mins for 10 to 50 mins by spectrophotometric analysis

Macrocyclic analogues of angiotensin IV (Ang IV, Val(1)-Tyr(2)-Ile(3)-His(4)-Pro(5)-Phe(6)) targeting the insulin-regulated aminopeptidase (IRAP) have been designed, synthesized, and evaluated biologically. Replacement of His(4)-Pro(5)-Phe(6) by a 2-(aminomethyl)phenylacetic acid (AMPAA) moiety and of Val(1) and Ile(3) by amino acids bearing olefinic side chains followed by macrocyclization more ..
_
   
 Tested Compounds
 Tested Compounds
All(16)
 
 
Active(16)
 
 
 Tested Substances
 Tested Substances
All(16)
 
 
Active(16)
 
 
 Related BioAssays
 Related BioAssays
AID: 601497
Data Source: ChEMBL (751648)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-02-15
Modify Date: 2013-11-17

Data Table ( Complete ):           Active    All
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: 16
Description:
Title: Potent macrocyclic inhibitors of insulin-regulated aminopeptidase (IRAP) by olefin ring-closing metathesis.

Abstract: Macrocyclic analogues of angiotensin IV (Ang IV, Val(1)-Tyr(2)-Ile(3)-His(4)-Pro(5)-Phe(6)) targeting the insulin-regulated aminopeptidase (IRAP) have been designed, synthesized, and evaluated biologically. Replacement of His(4)-Pro(5)-Phe(6) by a 2-(aminomethyl)phenylacetic acid (AMPAA) moiety and of Val(1) and Ile(3) by amino acids bearing olefinic side chains followed by macrocyclization provided potent IRAP inhibitors. The impact of the ring size and the type (saturated versus unsaturated), configuration, and position of the carbon-carbon bridge was assessed. The ring size generally affects the potency more than the carbon-carbon bond characteristics. Replacing Tyr(2) by beta(3)hTyr or Phe is accepted, while N-methylation of Tyr(2) is deleterious for activity. Removal of the carboxyl group in the C-terminal slightly reduced the potency. Inhibitors 7 (K(i) = 4.1 nM) and 19 (K(i) = 1.8 nM), both encompassing 14-membered ring systems connected to AMPAA, are 10-fold more potent than Ang IV and are also more selective over aminopeptidase N (AP-N). Both compounds displayed high stability against proteolysis by metallopeptidases.
(PMID: 21476495)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Categorized Comment
ChEMBL Assay Type: Binding

ChEMBL Assay Data Source: Scientific Literature

ChEMBL Target ID: 11239

ChEMBL Target Type: Target is a single protein chain

Result Definitions
Show more
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Ki*Ki PubChem standard valueFloatμM
2BEIBinding Efficiency Index(nM)Float
3SEISurface 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)
Classification
PageFrom: