Page 46 - I. Chemical biology and drug discovery
P. 46
[I. Chemical biology and drug discovery-25]
Preparation of novel fluorescent inhibitors with PSMA
targeting and hypoxia moiety and their evaluation in
prostate cancer
Young-Do Kwon¹, Hee-Kwon Kim¹˙*
¹Department of Nuclear Medicine, Jeonbuk National University, Jeonju 54907, Republic of Korea
Prostate cancer is commonly found cancers in men, and causes death of lots of men. It was known that prostate-
specific membrane antigen (PSMA), which is a 750 amino acid type II glycoprotein, were highly over expressed on
prostate cancer. Thus, PSMA is considered as a promising target for study of prostate cancer. Besides, hypoxia can
be found in lots of solid tumor when oxygen is decreased. Herein, novel multifunctional fluorescent PSMA inhibitors
containing PSMA target key moiety and tumor hypoxia sensitive moiety were designed. Novel PSMA inhibitors were
prepared using Lysine structure to link glutamate-urea-lysine (GUL) structure for the PSMA targeting, 2-
nitroimidazole for the hypoxia-sensitive moiety, and then imaging probes (near-infrared fluorophore) was attached
to the PSMA inhibitor moiety. PSMA binding assay indicated that novel inhibitors showed high binding affinities to
prostate cancer cell. In additions, animal studies suggested that new type of multifunction strategy can be a
promising study to enhance diagnosis and therapy of prostate cancer.
