PMID: 25742792Mar 7, 2015Paper

Computational design, chemical synthesis, and biological evaluation of a novel ERK inhibitor (BL-EI001) with apoptosis-inducing mechanisms in breast cancer

Oncotarget
Bo LiuJian Huang

Abstract

Extracellular signal-regulated kinase1/2 (ERK1/2) plays a crucial role in the resistance of apoptosis in carcinogenesis; however, its targeted small-molecule inhibitors still remain to be discovered. Thus, in this study, we computationally and experimentally screened a series of small-molecule inhibitors targeting ERK toward different types of human breast cancer cells. Subsequently, we synthesized some candidate ERK inhibitors, identified a novel ERK inhibitor (BL-EI001) with anti-proliferative activities, and analyzed the BL-EI001/ERK complex. Moreover, we found that BL-EI001 induced breast cancer cell apoptosis via mitochondrial pathway but independent on Ras/Raf/MEK pathway. In addition, we carried out proteomics analyses for exploring some possible BL-EI001-induced apoptotic pathways, and further found that BL-EI001-induced apoptosis affected ERK phosphorylation in breast cancer. Further, we found that BL-EI001 bear anti-tumor activities without remarkable toxicities, and also induced mitochondrial apoptosis by targeting ERK in vivo. Taken together, these results demonstrate that in silico design and experimental discovery of a synthesized small-molecule ERK inhibitor (BL-EI001)as a potential novel apoptosis-inducing drug ...Continue Reading

References

Mar 10, 2001·Nature·L Chang, M Karin
Sep 6, 2005·Biochemical and Biophysical Research Communications·Makoto OhoriTakashi Fujii
Jun 28, 2006·Cancer Science·Satoru ToriiEisuke Nishida
Nov 7, 2006·IUBMB Life·Zhimin Lu, Shuichan Xu
May 15, 2007·Oncogene·A S DhillonW Kolch
Apr 17, 2009·RNA·P Therese LangIrwin D Kuntz
Jun 25, 2009·Nature Reviews. Cancer·Thomas G Cotter
Jan 19, 2010·Biochimica Et Biophysica Acta·Eun Kyung Kim, Eui-Ju Choi
Aug 3, 2010·Current Opinion in Biotechnology·Inna N Lavrik
Nov 3, 2010·Cancer Letters·Jun-jie LiuJin-ku Bao
Dec 3, 2010·Current Opinion in Genetics & Development·John Brognard, Tony Hunter
Mar 10, 2012·Molecular Cancer Therapeutics·Georgia HatzivassiliouMark R Lackner
May 10, 2012·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Robert Roskoski
Nov 2, 2013·Molecular and Cellular Biochemistry·Cuijuan QianJianmin Si
Sep 10, 2014·Nature Chemical Biology·Apirat ChaikuadStefan Knapp

❮ Previous
Next ❯

Citations

Feb 5, 2019·Chemistry, an Asian Journal·Xiaohe TianGiuseppe Battaglia
Jun 30, 2021·Journal of Cancer Research and Clinical Oncology·Karen BräutigamFrank Köster

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.