A 5-fluorodeoxyuridine prodrug as targeted therapy for prostate cancer.
A method for targeted delivery of the cytotoxic agent 5-fluorodeoxyuridine (FudR) (1) to sites of metastatic prostate cancer is described. The prodrug was synthesized by coupling the active drug (FudR) to the PSA-peptide via a self-cleaving diamino acid linker to produce HSSKLQ-Leu-Aib-FudR. This prodrug serves as a substrate for prostate specific antigen (PSA). This approach permitted efficient conversion of the inactive prodrug back to the active cytotoxic state by the enzymatic activity of PSA which is highly expressed by prostate cells.
Mhaka
Annastasiah
A
Department of Experimental Therapeutics, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA.
Denmeade
Sam R
SR
Yao
Wei
W
Isaacs
John T
JT
Khan
Saeed R
SR
D016923:Cell Death / Q000187:drug effects; D016503:Drug Delivery Systems; D005467:Floxuridine / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism; D011355:Prodrugs / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D012661:Semen / Q000201:enzymology; D014407:Tumor Cells, Cultured
D010446:Peptide Fragments; D011355:Prodrugs; D005467:Floxuridine; D017430:Prostate-Specific Antigen