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BioAssay: AID 238832

Inhibition constant of anion against human carbonic anhydrase isozyme hCA IX; NT = not tested

A detailed inhibition study of five carbonic anhydrase (CA, EC 4.2.1.1) isozymes with inorganic phosphates, carbamoyl phosphate, the antiviral phosphonate foscarnet as well as formate is reported. The cytosolic isozyme hCA I was weakly inhibited by neutral phosphate, strongly inhibited by carbamoyl phosphate (K(I) of 9.4 microM), and activated by hydrogen- and dihydrogenphosphate, foscarnet and more ..
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 Tested Compounds
 Tested Compounds
All(1)
 
 
Inconclusive(1)
 
 
 Tested Substances
 Tested Substances
All(1)
 
 
Inconclusive(1)
 
 
 Related BioAssays
 Related BioAssays
AID: 238832
Data Source: ChEMBL (302926)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-24
Modify Date: 2014-08-23

Data Table ( Complete ):           View All Data
Target
Sequence: RecName: Full=Carbonic anhydrase 9; AltName: Full=Carbonate dehydratase IX; AltName: Full=Carbonic anhydrase IX; Short=CA-IX; Short=CAIX; AltName: Full=Membrane antigen MN; AltName: Full=P54/58N; AltName: Full=Renal cell carcinoma-associated antigen G250; Short=RCC-associated antigen G250; AltName: Full=pMW1; Flags: Precursor
Description ..   
Protein Family: alpha_CA_IX
Comment ..   

Gene:CA9     Related Protein 3D Structures     More BioActivity Data..
Tested Compound:
Description:
Title: Carbonic anhydrase inhibitors. Interaction of isozymes I, II, IV, V, and IX with phosphates, carbamoyl phosphate, and the phosphonate antiviral drug foscarnet.

Abstract: A detailed inhibition study of five carbonic anhydrase (CA, EC 4.2.1.1) isozymes with inorganic phosphates, carbamoyl phosphate, the antiviral phosphonate foscarnet as well as formate is reported. The cytosolic isozyme hCA I was weakly inhibited by neutral phosphate, strongly inhibited by carbamoyl phosphate (K(I) of 9.4 microM), and activated by hydrogen- and dihydrogenphosphate, foscarnet and formate (best activator foscarnet, K(A)=12 microM). The cytosolic isozyme hCA II was weakly inhibited by all the investigated anions, with carbamoyl phosphate showing a K(I) of 0.31 mM. The membrane-associated isozyme hCA IV was the most sensitive to inhibition by phosphates/phosphonates, showing a K(I) of 84 nM for PO(4)(3-), of 9.8 microM for HPO(4)(2-), and of 9.9 microM for carbamoyl phosphate. Foscarnet was the best inhibitor of this isozyme (K(I) of 0.82 mM) highly abundant in the kidneys, which may explain some of the renal side effects of the drug. The mitochondrial isozyme hCA V was weakly inhibited by all phosphates/phosphonates, except carbamoyl phosphate, which showed a K(I) of 8.5 microM. Thus, CA V cannot be the isozyme involved in the carbamoyl phosphate synthetase I biosynthetic reaction, as hypothesized earlier. Furthermore, the relative resistance of CA V to inhibition by inorganic phosphates suggests an evolutionary adaptation of this mitochondrial isozyme to the presence of high concentrations of such anions in these energy-converting organelles, where high amounts of ATP are produced by ATP synthetase, from ADP and inorganic phosphates. The transmembrane, tumor-associated isozyme hCA IX was on the other hand slightly inhibited by all these anions.
(PMID: 15501037)
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
1Ki activity commentKi activity commentString
2Ki standard flagKi standard flagInteger
3Ki qualifierKi qualifierString
4Ki published valueKi published valueFloatmM
5Ki standard valueKi standard valueFloat

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