Doxorubicin Prodrug L-377,202

**Semantic type:** Amino Acid, Peptide, or Protein|Antibiotic|Pharmacologic Substance

**Definition:** A prodrug in which a peptide is covalently conjugated with the anthracycline antineoplastic antibiotic doxorubicin. This complex is hydrolyzed by the enzyme prostate-specific antigen (PSA), resulting in the formation of doxorubicin and leucine-doxorubicin. Selective targeting of these drugs to prostate tumor cells occurs because the hydrolyzing PSA enzyme is localized to the prostate gland. Doxorubicin and leucine-doxorubicin intercalate into DNA and interacts with topoisomerase II, thereby inhibiting DNA replication and repair and RNA and protein synthesis. These agents also produce toxic free-radical intermediates and interact with cell membrane lipids causing lipid peroxidation.

**Synonyms:** - 5,12-Naphthacenedione, 10-((3-(((4R)-1-(4-carboxy-1-oxobutyl)-4-hydroxy-L-prolyl-L-alanyl-L-seryl-(2S)-2-cyclohexylglycyl-L-glutaminyl-L-seryl-L-leucyl)amino)-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy)-7,8,9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, (8S,10S)- - L-377,202 - L-377202 - L-377202