2-5a LIGANDS - A new concept for the treatment of prostate cancer

被引：8

作者：

Cramer, Hagen ^{[1
]}

Okicki, James R. ^{[1
]}

Rho, Taikyun ^{[1
]}

Wang, Xinning ^{[2
]}

Silverman, Robert H. ^{[2
]}

Heston, Warren D. W. ^{[2
]}

机构：

[1] Ridgeway Biosyst Inc, Cleveland, OH USA

[2] Cleveland Clin Fdn, Cleveland, OH USA

来源：

NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS | 2007年 / 26卷 / 10-12期

关键词：

PSMA; RBI; 1033; inhibitory activitty;

D O I：

10.1080/15257770701542652

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

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

引用

页码：1471 / 1477

页数：7

共 27 条

[1]

Targeted systemic therapy of prostate cancer with a monoclonal antibody to prostate-specific membrane antigen [J].