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BioAssay: AID 456399

Inhibition of human recombinant carbonic anhydrase 5A by stopped flow CO2 hydration method

We have investigated the enzyme inhibition characteristics of a natural product (NP)-based phenolic library against a panel of human carbonic anhydrases (hCAs, EC 4.2.1.1) which included hCAs I and II (cytosolic) and hCA VA/VB (mitochondrial isoforms). Most of these compounds were weak, micromolar inhibitors of the two cytosolic hCAs (K(I)s >10 microM) but showed good hCA VA/VB inhibitory more ..
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 Tested Compounds
 Tested Compounds
All(30)
 
 
Active(30)
 
 
 Tested Substances
 Tested Substances
All(30)
 
 
Active(30)
 
 
AID: 456399
Data Source: ChEMBL (607457)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-07-30
Modify Date: 2014-05-26

Data Table ( Complete ):           Active    All
Target
Sequence: RecName: Full=Carbonic anhydrase 5A, mitochondrial; AltName: Full=Carbonate dehydratase VA; AltName: Full=Carbonic anhydrase VA; Short=CA-VA; Flags: Precursor
Description ..   
Protein Family: alpha_CA_V
Comment ..   

Gene:CA5A     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: 30
Description:
Title: Carbonic anhydrase inhibitors. Identification of selective inhibitors of the human mitochondrial isozymes VA and VB over the cytosolic isozymes I and II from a natural product-based phenolic library.

Abstract: We have investigated the enzyme inhibition characteristics of a natural product (NP)-based phenolic library against a panel of human carbonic anhydrases (hCAs, EC 4.2.1.1) which included hCAs I and II (cytosolic) and hCA VA/VB (mitochondrial isoforms). Most of these compounds were weak, micromolar inhibitors of the two cytosolic hCAs (K(I)s >10 microM) but showed good hCA VA/VB inhibitory activity with inhibition constants in the range of 70-125 nM. The selectivity ratios for inhibiting the mitochondrial over the cytosolic isoforms for these phenol derivatives were in the range of 120-3800, making them the most isoform-selective compounds for inhibiting hCA VA/VB known to date. The CA VA/VB enzymes are involved in biosynthetic processes such as gluconeogenesis, lipogenesis and ureagenesis, and no pharmacological inhibitors with good selectivity are currently available. Thus the NP inhibitors identified during these studies are excellent leads for obtaining even more effective compounds that selectively target mitochondrial hCAs, and also have the potential to be used as tools for understanding the physiological processes that are regulated by the two mitochondrial CA isoforms.
(PMID: 19962903)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Categorized Comment
Assay Type: Binding

Assay Data Source: Scientific Literature

BAO: Assay Format: biochemical format

Target Type: Target is a single protein chain

Protein Target Class: enzyme lyase

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

Data Table (Concise)
Classification
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