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BioAssay: AID 627431

Irreversible inhibition of PAD3 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(4)
 
 
Inconclusive(1)
 
 
Unspecified(3)
 
 
 Tested Substances
 Tested Substances
All(4)
 
 
Inconclusive(1)
 
 
Unspecified(3)
 
 
 Related BioAssays
 Related BioAssays
AID: 627431
Data Source: ChEMBL (776937)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-09-09
Modify Date: 2014-08-25

Data Table ( Complete ):           View All Data
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: 104333
Target Type: SINGLE PROTEIN
Pref Name: Protein-arginine deiminase type-3
Synonyms: Peptidylarginine deiminase III;Protein-arginine deiminase type III;Protein-arginine deiminase type-3;
Gene Name: PADI3;PDI3;
Protein Accession: Q9ULW8;
Protein GI: 56757696;
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

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/min
5Kinact standard valueKinact standard valueFloat/min

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