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The rediscovery of DON (6-diazo-5-oxo-L-norleucine)
Abstract:
DON (6-diazo-5-oxo-L-norleucine) and azotomycin are glutamine antagonists that were tested in human malignancies in the 1950s. Azotomycin demonstrated significant activity in colorectal cancer. DON is probably the active form of azotomycin. Recent impressive results for both of these agents in human tumor xenografts (especially the CX-2 colon tumor) have stimulated renewed clinical interest in DON, the more readily available agent. DON mechanism of action, clinical pharmacology, previous clinical data, and current phase I studies are discussed.
Insights
6-diazo-5-oxo-L-norleucine (DON) and azotomycin, glutamine antagonists, show renewed interest for colorectal cancer treatment. DON, the active form, demonstrated efficacy in xenografts, prompting current clinical studies.
Area of Science:
- Oncology
- Pharmacology
- Cancer Research
Background:
- DON (6-diazo-5-oxo-L-norleucine) and azotomycin are glutamine antagonists investigated for cancer in the 1950s.
- Azotomycin showed significant activity in colorectal cancer, with DON potentially being its active form.
- Recent success in human tumor xenografts has revived interest in DON for cancer therapy.
Purpose of the Study:
- To review the mechanism of action of DON.
- To discuss the clinical pharmacology and previous clinical data of DON.
- To provide an overview of current Phase I studies involving DON.
Main Methods:
- Literature review of DON and azotomycin in cancer treatment.
- Analysis of previous clinical trial data.
- Summary of ongoing Phase I clinical studies.
Main Results:
- DON and azotomycin are glutamine antagonists with historical efficacy.
- DON demonstrated significant activity in preclinical models, particularly colon tumors.
- Renewed clinical interest is driven by recent xenograft study results.
Conclusions:
- DON is a promising agent for colorectal cancer, warranting further investigation.
- Understanding DON's mechanism and pharmacology is crucial for its clinical application.
- Current Phase I studies aim to establish DON's safety and efficacy profile.