Acivicin

Acivicin is not a therapeutic target but rather a small molecule drug, specifically a glutamine analog and antineoplastic antibiotic originally isolated from the bacterium Streptomyces sviceus. It acts as a potent, irreversible inhibitor of several glutamine-utilizing enzymes, including gamma-glutamyltransferase (GGT) and various amidotransferases involved in de novo purine and pyrimidine biosynthesis. By mimicking glutamine, acivicin competes for the active sites of these enzymes, leading to the disruption of nucleotide synthesis and cellular metabolism, which inhibits the growth of rapidly dividing tumor cells. Although it demonstrated significant anti-tumor activity in preclinical models and entered clinical trials for various cancers, its development was largely discontinued due to dose-limiting toxicities, particularly severe central nervous system side effects such as ataxia, hallucinations, and lethargy.

Other names

AT-125U-42126L-(alphaS,5S)-alpha-Amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid

Irreversible inhibition of gamma-glutamyltransferase and various glutamine-dependent amidotransferases