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:3.4.24.23 (
MMP
)
4,246
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
6-Methoxypurine arabinoside (ara-M) is a highly selective inhibitor of varicella-zoster virus (VZV). It belongs to a class of purine arabinosides whose anti-VZV activity in vitro correlates with substrate utilization by the VZV-encoded thymidine kinase (TK) (D. R. Averett, G. W. Koszalka, J. A. Fyfe, G. B. Roberts, D. J. M. Purifoy, and T. A. Krenitsky, Antimicrob Agents Chemother. 35:851-857, 1991). In this study, the mechanism of action of
ara
-M was explored. VZV-infected human fibroblasts selectively accumulated
ara
-M and its phosphorylated metabolites, whereas in uninfected fibroblasts or in those infected with a TK-deficient strain of VZV, there was virtually no cellular uptake of
ara
-M. The major intracellular metabolite of
ara
-M in VZV-infected cells was identified as the triphosphate of adenine arabinoside (ara-ATP). Appreciable levels of
ara
-ADP, ara-AMP, and
ara
-
MMP
were also detected. However, di- or triphosphorylated forms of
ara
-M were not detected. Moreover, in VZV-infected cells, the concentrations of
ara
-ATP which accumulated in the presence of
ara
-M were up to eightfold higher than those generated with
ara
-A itself. In contrast, in uninfected cells, the levels of
ara
-ATP which accumulated in the presence of
ara
-M were barely detectable. Clearly, Ara-M activation was dependent on the activity of the virus-encoded TK, while
ara
-A anabolism resulted primarily from the activity of host cell enzymes. Therefore,
ara
-M selectively generates the DNA polymerase inhibitor
ara
-ATP in the VZV-infected cell.
...
PMID:Selective anabolism of 6-methoxypurine arabinoside in varicella-zoster virus-infected cells. 172 79
BHAC-
MMP
therapy, a combination of behenoyl-
ara
-C, mitoxantrone, 6-mercaptopurine and prednisolone, was applied to 49 patients with acute leukemia for remission induction. Complete remission was obtained in 6 out of 11 previously untreated patients (55%), and in 16 of 38 pretreated patients (42%). Median duration of complete remission was 41 weeks in previously treated patients, while 67% of untreated patients were still in complete remission. Most frequent side effects other than hematological toxicities were gastrointestinal disturbances, and GPT elevation etc., although most of these were not severe. In conclusion, BHAC-
MMP
therapy seems to be very promising for remission induction or for possible intensification treatment for acute leukemia.
...
PMID:[A phase III study of BHAC-MMP (behenoyl-ara-C, mitoxantrone, 6-mercaptopurine prednisolone) in acute leukemia. Hanshin Cooperative Study Group of Hematological Disorders]. 353 Jan 40
