Biochemical pharmacology and antitumor properties of 4-amino-8-[beta-D-ribofuranosylamino]pyrimido-[5,4-d]pyrimidine.
1. APP is activated by adenosine kinase to its 5'-phosphate (APP-MP). 2. APP-MP inhibits PRPP synthetase, and depletes cellular PRPP and purine and pyrimidine nucleotides. 3. APP inhibits synthesis of DNA and RNA, and blocks cells in G1 phase of the cell cycle. 4. APP retains full activity against MDR cells. 5. APP is equally active against quiescent and proliferating CHO cells. 6. APP has only weak activity against L1210 leukemia in vivo, but has substantial activity against mammary carcinoma 16/c. 7. In vitro, APP has a relatively high ratio of solid tumor: leukemia activity.
Jackson
R C
RC
Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105.
Boritzki
T J
TJ
Cook
P D
PD
Hook
K E
KE
Leopold
W R
WR
Fry
D W
DW
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy*; D051379:Mice; D010770:Phosphotransferases / Q000037:antagonists & inhibitors*; D011687:Purines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011741:Pyrimidine Nucleosides / Q000494:pharmacology / Q000627:therapeutic use; D012268:Ribose-Phosphate Pyrophosphokinase / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000964:Antimetabolites, Antineoplastic; C011650:NSC 283867; D011687:Purines; D011741:Pyrimidine Nucleosides; D010770:Phosphotransferases; D012268:Ribose-Phosphate Pyrophosphokinase