一二三四区视频,亚洲少妇熟女色,日本久热无码视频网,欧美国产日韩大尺度,亚洲a视频,久久少妇一区二区,日韩999无码视频,刺激久久久久久久,啊啊啊啊不要啊在线

ChemicalBook >> journal list >> Cancers >>article
Cancers

Cancers

IF: 4.4
Download PDF

N-Benzylated 5-Hydroxybenzothiophene-2-carboxamides as Multi-Targeted Clk/Dyrk Inhibitors and Potential Anticancer Agents

Published:27 May 2024 DOI: 10.3390/cancers16112033 PMID: 38893153
Noha Mostafa,?Po-Jen Chen,?Sarah S Darwish,?Yu-Chieh Su,?Ming-Hua Shiao,?Gary A Piazza,?Ashraf H Abadi,?Matthias Engel,?Mohammad Abdel-Halim

Abstract

Numerous studies have reported that Dyrk1A, Dyrk1B, and Clk1 are overexpressed in multiple cancers, suggesting a role in malignant disease. Here, we introduce a novel class of group-selective kinase inhibitors targeting Dyrk1A, Dyrk1B, and Clk1. This was achieved by modifying our earlier selective Clk1 inhibitors, which were based on the 5-methoxybenzothiophene-2-carboxamide scaffold. By incorporating a 5-hydroxy group, we increased the potential for additional hydrogen bond interactions that broadened the inhibitory effect to include Dyrk1A and Dyrk1B kinases. Within this series, compounds 12 and 17 emerged as the most potent multi-kinase inhibitors against Dyrk1A, Dyrk1B, and Clk1. Furthermore, when assessed against the most closely related kinases also implicated in cancer, the frontrunner compounds revealed additional inhibitory activity against Haspin and Clk2. Compounds 12 and 17 displayed high potency across various cancer cell lines with minimal effect on non-tumor cells. By examining the effect of these inhibitors on cell cycle distribution, compound 17 retained cells in the G2/M phase and induced apoptosis. Compounds 12 and 17 could also increase levels of cleaved caspase-3 and Bax, while decreasing the expression of the antiapoptotic Bcl-2 protein. These findings support the further study and development of these compounds as novel anticancer therapeutics.

Similar articles

IF:9.1

Multi-targeted prevention of cancer by sulforaphane

Cancer letters John D. Clarke , Roderick H. Dashwood ,etc Published: 8 October 2008
IF:6.8

New Bis-thiazolium Analogues as Potential Antimalarial Agents: Design, Synthesis, and Biological Evaluation

Journal of Medicinal Chemistry Sergio A. Caldarelli, Siham El Fangour,etc Published: 4 January 2013
IF:1.8

Synthesis of 2-Aminobenzophenone Derivatives and Their Anticancer Activity

Synthetic Communications Sandra Cortez-Maya,?E. Cortés,etc Published: 1 January 2012
班戈县| 日喀则市| 秦安县| 喜德县| 万年县| 昌吉市| 西林县| 西城区| 保德县| 穆棱市| 松江区| 洞头县| 乌兰浩特市| 丹阳市| 瑞安市| 四平市| 方山县| 区。| 建水县| 固阳县| 皮山县| 梁平县| 桐柏县| 哈尔滨市| 杭州市| 临夏县| 巴楚县| 响水县| 剑川县| 凤冈县| 页游| 钦州市| 高雄县| 大丰市| 辉县市| 林芝县| 迁西县| 临江市| 沂源县| 乐亭县| 张家口市|