期刊
MOLECULAR PHARMACEUTICS
卷 12, 期 7, 页码 2477-2483出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.5b00218
关键词
CCK2R; cholecystokinin 2 receptor; tubulysin; vinblastine; targeted therapy
资金
- Purdue University
As the delivery of selectively targeted cytotoxic agents via antibodies or small molecule ligands to malignancies has begun to show promise in the clinic, the need to identify and validate additional cellular targets for specific therapeutic delivery is critical. Although a multitude of cancers have been targeted using the folate receptor, PSMA, bombesin receptor, somatostatin receptor, LHRH, and alpha(v)beta(3), there is a notable lack of specific small molecule ligand/receptor pairs to cellular targets found within cancers of the GI tract. Because of the selective GI tract expression of the cholecystokinin 2 receptor (CCK2R), we undertook the creation of conjugates that would deliver microtubule-disrupting drugs to malignancies through the specific targeting of CCK2R via a high affinity small molecule ligand. The c-ytotoxic activity of these conjugates were shown to be receptor mediated in vitro and in vivo with xenograft mouse models exhibiting delayed growth or regression of tumors that expressed CCK2R Overall, this work demonstrates that ligands to CCK2R can be used to create selectively targeted therapeutic conjugates.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据