Synthesis and biological analysis of prostate-specific membrane antigen-targeted anticancer prodrugs

Sumith A. Kularatne, Chelvam Venkatesh, Hari Krishna R. Santhapuram, Kevin Wang, Balasubramanian Vaitilingam, Walter A. Henne, Philip Low

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

Ligand-targeted therapeutics have increased in prominence because of their potential for improved potency and reduced toxicity. However, with the advent of personalized medicine, a need for greater versatility in ligand-targeted drug design has emerged, where each tumor-targeting ligand should be capable of delivering a variety of therapeutic agents to the same tumor, each therapeutic agent being selected for its activity on a specific patient's cancer. In this report, we describe the use of a prostate-specific membrane antigen (PSMA)-targeting ligand to deliver multiple unrelated cytotoxic drugs to human prostate cancer (LNCaP) cells. We demonstrate that the PSMA-specific ligand, 2-[3-(1, 3-dicarboxy propyl)ureido] pentanedioic acid, is capable of mediating the targeted killing of LNCaP cells with many different therapeutic warheads. These results suggest that flexibility can be designed into ligand-targeted therapeutics, enabling adaptation of a single targeting ligand for the treatment of patients with different sensitivities to different chemotherapies.

Original languageEnglish (US)
Pages (from-to)7767-7777
Number of pages11
JournalJournal of Medicinal Chemistry
Volume53
Issue number21
DOIs
StatePublished - Nov 11 2010

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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