Abstract
Several potent prostate specific membrane antigen (PSMA) inhibitors have been described recently. We generated a PSMA-specific 2-5A ligand called RBI 1033 by linking 2-5A to the N-acetylaspartylglutamate (NAAG)-based inhibitor ZJ-24. We measured the inhibitory activity of RBI 1033 to the folate hydrolase activity of PSMA. Amazingly, we found that compared to ZJ-24 (IC50 = 53.9 nM), RBI 1033 was more than 10 times more potent (IC50 = 4.78 nM) as a folate hydrolase inhibitor, while SMCC 2-5A lacking the ZJ-24 part, did not show much activity (IC50 = 1974 nM). Also, RBI 1033's affinity to PSMA was found to be 10 times higher than ZJ-24 itself.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adenine Nucleotides / chemistry
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Adenine Nucleotides / pharmacology*
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Adenine Nucleotides / therapeutic use
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Antigens, Surface / chemistry
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Antineoplastic Agents / therapeutic use
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Endoribonucleases / chemistry
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Glutamate Carboxypeptidase II / antagonists & inhibitors*
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Glutamate Carboxypeptidase II / chemistry
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Humans
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Ligands
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Male
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Prostatic Neoplasms / drug therapy*
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Prostatic Neoplasms / enzymology
Substances
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Adenine Nucleotides
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Antigens, Surface
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Antineoplastic Agents
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Ligands
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RBI 1033
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Endoribonucleases
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2-5A-dependent ribonuclease
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FOLH1 protein, human
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Glutamate Carboxypeptidase II