Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.1.1.67 (
thiopurine methyltransferase
)
551
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Thiopurine drugs are used in the treatment of inflammatory bowel disease--as are sulphasalazine and its metabolite 5-aminosalicylic acid (ASA). S-Methylation catalyzed by
thiopurine methyltransferase
(
TPMT
) is a major pathway in the metabolism of thiopurines. The hypothesis was tested that
TPMT
might be inhibited by sulphasalazine or isomers of ASA.
Sulphasalazine
as well as 3-, 4- and 5-ASA inhibited recombinant human
TPMT
, with IC50 values of 78, 99, 2600 and 1240 microM, respectively. Kinetic studies demonstrated that the inhibition of
TPMT
by sulphasalazine and ASA isomers was non-competitive with regard to the thiopurine substrate, 6-MP, and was uncompetitive with regard to the methyl donor for the reaction, S-adenosyl-L-methionine. Our observations raise the possibility of a clinically significant drug-drug interaction in patients treated simultaneously with sulphasalazine and thiopurine drugs.
...
PMID:Sulphasalazine inhibition of thiopurine methyltransferase: possible mechanism for interaction with 6-mercaptopurine and azathioprine. 764 Jan 56
