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BioAssay: AID 318345

Activation of human recombinant CA9 catalytic domain by stopped-flow CO2 hydration method

The first activation study of the human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms associated to tumors, hCA IX and XII, with a small library of natural and non-natural amino acids as well as aromatic/heterocyclic amines is reported. hCA IX was activated efficiently by dopamine, adrenaline and heterocyclic amines possessing aminoethyl-/aminomethyl-moieties (K(A)s of 9 nM-1.07 microM), whereas more ..
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 Tested Compounds
 Tested Compounds
All(18)
 
 
Active(16)
 
 
Unspecified(2)
 
 
 Tested Substances
 Tested Substances
All(18)
 
 
Active(16)
 
 
Unspecified(2)
 
 
AID: 318345
Data Source: ChEMBL (466371)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-25
Modify Date: 2014-05-25

Data Table ( Complete ):           Active    All
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..
BioActive Compounds: 16
Description:
Title: Carbonic anhydrase activators: activation of the human tumor-associated isozymes IX and XII with amino acids and amines.

Abstract: The first activation study of the human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms associated to tumors, hCA IX and XII, with a small library of natural and non-natural amino acids as well as aromatic/heterocyclic amines is reported. hCA IX was activated efficiently by dopamine, adrenaline and heterocyclic amines possessing aminoethyl-/aminomethyl-moieties (K(A)s of 9 nM-1.07 microM), whereas the best hCA XII activators were serotonin, L-adrenaline, 4-(2-aminoethyl)-morpholine and d-Phe (K(A) of 0.24-0.41 microM). Precise steric and electronic requirements are needed to be present in the molecules of effective hCA IX/hCA XII activators, in order to assure an adequate fit within the enzyme active site cavity for the formation of the enzyme-activator complex, and for an efficient proton transfer process within this complex, leading to the release of a proton and formation of the catalytically active, zinc-hydroxide species of the enzyme. Selective activation of these CA isoforms might be useful to develop pharmacologic tools or to understand whether some of these biogenic amines/amino acids may influence the progression of tumors overexpressing CA IX and/or CA XII.
(PMID: 18294854)
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
1KA activity commentKA activity commentString
2KA standard flagKA standard flagInteger
3KA qualifierKA qualifierString
4KA published valueKA published valueFloatμM
5KA standard valueKA standard valueFloatnM

Data Table (Concise)
Classification
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