SYNERGISTIC EFFECTS WITH INHIBITORS OF DENOVO PYRIMIDINE SYNTHESIS, ACIVICIN, AND N-(PHOSPHONACETYL)-L-ASPARTIC ACID
- 1 January 1981
- journal article
- research article
- Vol. 41 (9) , 3419-3423
Abstract
Acivicin, an inhibitor of L-glutamine-dependent amidotransferases, is active against the murine L1210 and P388 leukemia models. Cytidine triphosphate synthetase has been proposed as the primary target for this agent. Acivicin evidently is also an inhibitor of de novo pyrimidine biosynthesis. This inhibition results in the depletion of pyrimidine deoxyribonucleoside triphosphate pools and explains the effect of this agent on DNA synthesis. Acivicin is synergistic with N-(phosphonacetyl)-L-aspartic acid, another inhibitor of de novo pyrimidine synthesis. The combination of these agents results in a more than additive depletion of deoxycytidine triphosphate pools which may account for their synergism in inhibiting cellular growth. Thus, the inhibition of de novo pyrimidine synthesis by acivicin may be useful in modulating the effects of certain antimetabolites or other inhibitors of this pathway.This publication has 6 references indexed in Scilit:
- THERAPEUTIC EFFECTS OF ACIVICIN AND N-(PHOSPHONACETYL)-L-ASPARTIC ACID IN A BIOCHEMICALLY DESIGNED TRIAL AGAINST A N-(PHOSPHONACETYL)-L-ASPARTIC ACID-RESISTANT VARIANT OF THE LEWIS LUNG-CARCINOMA1981
- MECHANISM OF RESISTANCE OF VARIANTS OF THE LEWIS LUNG-CARCINOMA TO N-(PHOSPHONACETYL)-L-ASPARTIC ACID1981
- THERAPY FOR MOUSE-TUMORS AND HUMAN-TUMOR XENOGRAFTS WITH THE ANTI-TUMOR ANTIBIOTIC AT-1251979
- BIOCHEMICAL AND PHARMACOLOGICAL EFFECTS OF THE FERMENTATION-DERIVED ANTI-TUMOR AGENT, (ALPHA-S,5S)-ALPHA-AMINO-3-CHLORO-4,5-DIHYDRO-5-ISOXAZOLEACETIC ACID (AT-125)1979
- EFFECTS OF N-(PHOSPHONACETYL)-L-ASPARTATE ON MURINE TUMORS AND NORMAL TISSUES INVIVO AND INVITRO AND RELATIONSHIP OF SENSITIVITY TO RATE OF PROLIFERATION AND LEVEL OF ASPARTATE-TRANSCARBAMYLASE1978
- SYNERGY, ADDITIVISM AND ANTAGONISM IN IMMUNOSUPPRESSION - CRITICAL-REVIEW1977