Work

Renaissance of 6-Diazo-5-oxo-ʟ-norleucine (DON): Prodrug Strategy as a Promising Tool Leading to Potential Anticancer Drug

Year: 2025

Type: article

Abstract: The natural compound 6-diazo-5-oxo-ʟ-norleucine (DON) has shown promising anticancer activity in several preclinical and early clinical studies, but its further development has been hampered by adverse toxicity, mainly in the gastrointestinal tract. This review discusses the renaissance of DON through prodrug strategies. Using rational strategies, we have developed hundreds of tumor- and brain-targeted prodrugs with improved pharmacokinetic and pharmacodynamic properties and without severe toxicity. The most promising prodrug, sirpiglenastat, entered clinical trials in 2020 under the leadership of Dracen Pharmaceuticals and is currently being tested in combination with durvalumab in patients with fibrolamellar hepatocellular carcinoma.

Source: Chemické listy

DOI: 10.54779/chl20250274

Author: Lukáš Tenora

Institutions: Czech Academy of Sciences, Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry

Language: English

Topic: Synthesis and biological activity

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: diamond

OpenAlex ID: W4410353216

FWCI: 0.298

Cites:

Cited by: 1

Related to: 10