title: A 5-fluorodeoxyuridine prodrug as targeted therapy for prostate cancer.
abstract: 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.
authors.affiliation: Department of Experimental Therapeutics, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA.
authors.forename: Annastasiah
authors.initials: A
authors.lastname: Mhaka
authors.forename: Sam R
authors.initials: SR
authors.lastname: Denmeade
authors.forename: Wei
authors.initials: W
authors.lastname: Yao
authors.forename: John T
authors.initials: JT
authors.lastname: Isaacs
authors.forename: Saeed R
authors.initials: SR
authors.lastname: Khan
mesh_terms: 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
chemical_list: D010446:Peptide Fragments; D011355:Prodrugs; D005467:Floxuridine; D017430:Prostate-Specific Antigen