2-5A ligands--a new concept for the treatment of prostate cancer.
2-5A ligands--a new concept for the treatment of prostate cancer.
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2-5A配体——治疗前列腺癌的新概念。
DOI：
10.1080/15257770701542652
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Heston,WarrenDW
中科院分区：
文献类型：
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作者：
Cramer,Hagen;Okicki,JamesR;Rho,Taikyun;Wang,Xinning;Silverman,RobertH;Heston,WarrenDW
最近已经描述了几种有效的前列腺特异性膜抗原（PSMA）抑制剂。我们通过将2-5A连接到基于N-乙酰基谷氨酸盐（NAAG）的抑制剂ZJ-24来产生PSMA特异性2-5A配体，称为RBI 1033。我们测量了RBI 1033对PSMA的叶酸水解酶活性的抑制活性。令人惊讶的是，我们发现，与ZJ-24（IC 50 = 53.9 nM）相比，RBI 1033作为叶酸水解酶抑制剂的效力高出10倍（IC 50 = 4.78 nM），而缺乏ZJ-24部分的SMCC 2-5A没有显示出太多活性（IC 50 = 1974 nM）。此外，发现RBI 1033对PSMA的亲和力比ZJ-24本身高10倍。
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.