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BioAssay: AID 627430

Irreversible inhibition of PAD2 assessed as residual activity measured after 20 hrs by colorimetric assay

Protein arginine deiminase (PAD) activity is upregulated in a number of human diseases, including rheumatoid arthritis, ulcerative colitis, and cancer. These enzymes, there are five in humans (PADs 1-4 and 6), regulate gene transcription, cellular differentiation, and the innate immune response. Building on our successful generation of F- and Cl-amidine, which irreversibly inhibit all of the more ..
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 Tested Compounds
 Tested Compounds
All(3)
 
 
Inconclusive(3)
 
 
 Tested Substances
 Tested Substances
All(3)
 
 
Inconclusive(3)
 
 
 Related BioAssays
 Related BioAssays
AID: 627430
Data Source: ChEMBL (776936)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-09-09
Modify Date: 2014-05-26

Data Table ( Complete ):           All
Tested Compounds:
Description:
Title: The development of N-alpha-(2-carboxyl)benzoyl-N(5)-(2-fluoro-1-iminoethyl)-l-ornithine amide (o-F-amidine) and N-alpha-(2-carboxyl)benzoyl-N(5)-(2-chloro-1-iminoethyl)-l-ornithine amide (o-Cl-amidine) as second generation protein arginine deiminase (PAD) inhibitors.

Abstract: Protein arginine deiminase (PAD) activity is upregulated in a number of human diseases, including rheumatoid arthritis, ulcerative colitis, and cancer. These enzymes, there are five in humans (PADs 1-4 and 6), regulate gene transcription, cellular differentiation, and the innate immune response. Building on our successful generation of F- and Cl-amidine, which irreversibly inhibit all of the PADs, a structure-activity relationship was performed to develop second generation compounds with improved potency and selectivity. Incorporation of a carboxylate ortho to the backbone amide resulted in the identification of N-alpha-(2-carboxyl)benzoyl-N(5)-(2-fluoro-1-iminoethyl)-l-ornithine amide (o-F-amidine) and N-alpha-(2-carboxyl)benzoyl-N(5)-(2-chloro-1-iminoethyl)-l-ornithine amide (o-Cl-amidine), as PAD inactivators with improved potency (up to 65-fold) and selectivity (up to 25-fold). Relative to F- and Cl-amidine, the compounds also show enhanced potency in cellulo. As such, these compounds will be versatile chemical probes of PAD function.
(PMID: 21882827)
Comment
Putative Target:

ChEMBL Target ID: 104332
Target Type: SINGLE PROTEIN
Pref Name: Protein-arginine deiminase type-2
Synonyms: PAD-H19;Peptidylarginine deiminase II;Protein-arginine deiminase type II;Protein-arginine deiminase type-2;
Gene Name: KIAA0994 ;PADI2;PDI2;
Protein Accession: Q9Y2J8;
Protein GI: 7531171;
Organism: Homo sapiens
Tax ID: 9606
Target Classification: enzyme
Confidence: Homologous single protein target assigned
Relationship Type: Homologous protein target assigned
Categorized Comment
Assay Type: Binding

Assay Data Source: Scientific Literature

BAO: Assay Format: biochemical format

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Kinact activity commentKinact activity commentString
2Kinact standard flagKinact standard flagInteger
3Kinact qualifierKinact qualifierString
4Kinact published valueKinact published valueFloat
5Kinact standard valueKinact standard valueFloat

Data Table (Concise)
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