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BioAssay: AID 456400

Inhibition of human recombinant carbonic anhydrase 5B 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: 456400
Data Source: ChEMBL (607458)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-07-30
Modify Date: 2014-08-25

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

Gene:CA5B     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 - additional comments and annotations
From BioAssay Depositor:
Assay Type: Binding
Target Type: Target is a single protein chain
Assay Data Source: Scientific Literature
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)
Data Table ( Complete ):     View Active Data    View All Data
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