Inhibitors of L-asparagine synthetase, in vitro.
A systematic search has been made for inhibitors of L-asparagine synthetase (L-glutamine hydrolyzing, EC 6.3.5.4) from leukemia 5178Y/AR, a rodent neoplasm resistant to the oncolytic enzyme L-asparaginase (EC 3.5.1.1), The classes of chemicals examined in this search included substrate and product analogs, agents capable of reacting with sulfhydryl functions, and a variety of modifiers whose mechanism of interaction with proteins is known. In general, antagonists of L-glutamine and thiol reagents proved to be the most effective inhibitors of L-asparagine synthetase from this tumor source. Within these groups, certain structural prerequisites to inhibition are reported. Attempts to correlate oncolytic potency with enzyme-inhibitory potency were unsuccesful.
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000641:Ammonia / Q000494:pharmacology; D000818:Animals; D001215:Asparaginase / Q000494:pharmacology; D001217:Aspartate-Ammonia Ligase / Q000037:antagonists & inhibitors*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D011756:Diphosphates / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D004351:Drug Resistance; D005973:Glutamine / Q000031:analogs & derivatives / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D066298:In Vitro Techniques; D007555:Isoxazoles / Q000494:pharmacology; D007942:Leukemia, Experimental / Q000201:enzymology*; D008025:Ligases / Q000037:antagonists & inhibitors*; D008314:Malonates / Q000494:pharmacology; D008670:Metals / Q000494:pharmacology; D009607:Nitrosourea Compounds / Q000494:pharmacology; D013439:Sulfhydryl Reagents / Q000494:pharmacology
D011756:Diphosphates; D007555:Isoxazoles; D008314:Malonates; D008670:Metals; D009607:Nitrosourea Compounds; D013439:Sulfhydryl Reagents; D005973:Glutamine; D001224:Aspartic Acid; D000641:Ammonia; D000255:Adenosine Triphosphate; D006493:Heparin; D001215:Asparaginase; D008025:Ligases; D001217:Aspartate-Ammonia Ligase