TY - JOUR
T1 - Synthesis and biological analysis of prostate-specific membrane antigen-targeted anticancer prodrugs
AU - Kularatne, Sumith A.
AU - Venkatesh, Chelvam
AU - Santhapuram, Hari Krishna R.
AU - Wang, Kevin
AU - Vaitilingam, Balasubramanian
AU - Henne, Walter A.
AU - Low, Philip
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2010/11/11
Y1 - 2010/11/11
N2 - 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.
AB - 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.
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U2 - 10.1021/jm100729b
DO - 10.1021/jm100729b
M3 - Article
C2 - 20936874
AN - SCOPUS:78149279338
SN - 0022-2623
VL - 53
SP - 7767
EP - 7777
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 21
ER -