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Novel N-Methylated Cyclodepsipeptide Prodrugs for Targeted Cancer Therapy

التفاصيل البيبلوغرافية
العنوان: Novel N-Methylated Cyclodepsipeptide Prodrugs for Targeted Cancer Therapy
المؤلفون: Wu Su, Lijing Fang, Meiqing Li, Danyi Lu, Ximing Shao, Yulian Cheng, Yimin Zhou, Ke Liu, Chunlei Wu, Hongchang Li, Pengxin Wang, Zhehong Cheng
المصدر: Journal of Medicinal Chemistry. 64:991-1000
بيانات النشر: American Chemical Society (ACS), 2021.
سنة النشر: 2021
مصطلحات موضوعية: Tumor microenvironment, Chemistry, Drug Discovery, Toxicity, Molecular Medicine, Prodrug, Pharmacology, Cytotoxicity, Linker, In vitro, RGD motif, Conjugate
الوصف: Coibamide A (1) is a highly N-methylated cyclodepsipeptide with low nanomolar antiproliferative activities against various cancer cell lines. In previous work, we discovered a simplified analogue, [MeAla3-MeAla6]-coibamide (1a), which exhibited the same inhibitory abilities as coibamide A. Herein, to reduce the whole-body toxicity and improve the solubility of 1a, two novel peptide-drug conjugates RGD-SS-CA (2) and RGD-VC-CA (3) were designed, synthesized, and evaluated. Composed of cyclodepsipeptide 1a, a tumor-homing RGD motif, and a conditionally labile linker, the conjugates are expected to release 1a tracelessly in specific tumor microenvironments. Compared with RGD-VC-CA (3), RGD-SS-CA (2) proved to be superior in in vitro drug release and cytotoxicity tests. Notably, intravenous injection of RGD-SS-CA (2) into mice-bearing human tumor xenografts induced significant tumor growth suppression with negligible toxicity. Therefore, as a novel prodrug of the coibamide A analogue, conjugate 2 has great potential for further exploration in cancer drug discovery.
تدمد: 1520-4804
0022-2623
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::8cf33dfa08530c1fdadec9b322a4d102
https://doi.org/10.1021/acs.jmedchem.0c01387
حقوق: CLOSED
رقم الأكسشن: edsair.doi...........8cf33dfa08530c1fdadec9b322a4d102
قاعدة البيانات: OpenAIRE
الوصف
تدمد:15204804
00222623