Publications by authors named "Guang-Xi Yu"

4 Publications

  • Page 1 of 1

Drug Discovery Targeting Focal Adhesion Kinase (FAK) as a Promising Cancer Therapy.

Molecules 2021 Jul 13;26(14). Epub 2021 Jul 13.

Key Laboratory of Advanced Drug Preparation Technologies (Ministry of Education), Institute of Drug Discovery & Development, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.

FAK is a nonreceptor intracellular tyrosine kinase which plays an important biological function. Many studies have found that FAK is overexpressed in many human cancer cell lines, which promotes tumor cell growth by controlling cell adhesion, migration, proliferation, and survival. Therefore, targeting FAK is considered to be a promising cancer therapy with small molecules. Many FAK inhibitors have been reported as anticancer agents with various mechanisms. Currently, six FAK inhibitors, including (Phase I), (Phase II), (Phase I), (Phase I), (Phase I), and (Phase I) are undergoing clinical trials in different phases. Up to now, there have been many novel FAK inhibitors with anticancer activity reported by different research groups. In addition, FAK degraders have been successfully developed through "proteolysis targeting chimera" (PROTAC) technology, opening up a new way for FAK-targeted therapy. In this paper, the structure and biological function of FAK are reviewed, and we summarize the design, chemical types, and activity of FAK inhibitors according to the development of FAK drugs, which provided the reference for the discovery of new anticancer agents.
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http://dx.doi.org/10.3390/molecules26144250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308130PMC
July 2021

Discovery of Novel Diarylamide -Containing Heterocyclic Derivatives as New Tubulin Polymerization Inhibitors with Anti-Cancer Activity.

Molecules 2021 Jul 2;26(13). Epub 2021 Jul 2.

Key Laboratory of Advanced Drug Preparation Technologies (Ministry of Education), Institute of Drug Discovery & Development, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.

Tubulin has been regarded as an attractive and successful molecular target in cancer therapy and drug discovery. Vicinal diaryl is a simple scaffold found in many colchicine site tubulin inhibitors, which is also an important pharmacophoric point of tubulin binding and anti-cancer activity. As the continuation of our research work on colchicine binding site tubulin inhibitors, we designed and synthesized a series of diarylamide -containing heterocyclic derivatives by the combination of vicinal diaryl core and -containing heterocyclic skeletons into one hybrid though proper linkers. Among of these compounds, compound containing a 5-methoxyindole group exhibited the most potent inhibitory activity against the tested three human cancer cell lines (MGC-803, PC-3 and EC-109) with IC values of 1.56 μM, 3.56 μM and 14.5 μM, respectively. Besides, the SARs of these compounds were preliminarily studied and summarized. The most active compound produced the inhibition of tubulin polymerization in a dose-dependent manner and caused microtubule network disruption in MGC-803 cells. Therefore, compound was identified as a novel tubulin polymerization inhibitor targeting the colchicine binding site. In addition, the results of molecular docking also suggested compound could tightly bind into the colchicine binding site of β-tubulin.
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http://dx.doi.org/10.3390/molecules26134047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272053PMC
July 2021

Discovery of indoline derivatives as anticancer agents via inhibition of tubulin polymerization.

Bioorg Med Chem Lett 2021 Aug 20;45:128131. Epub 2021 May 20.

School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China. Electronic address:

Human esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers in human digestive system. It is necessary to discover novel antitumor agents for the treatment of esophageal cancers because of its poor prognosis. Indoline has been reported as an efficient anticancer fragment to design novel anticancer agents. In this work, indoline derivatives were designed, synthesized and explored their anticancer activity. Compound 9d, which exhibited potent antiproliferative activity with IC values of 1.84 μM (MGC-803 cells), 6.82 μM (A549 cells), 1.61 μM (Kyse30 cells), 1.49 μM (Kyse450 cells), 2.08 μM (Kyse510 cells) and 2.24 μM (EC-109 cells), respectively. The most active compound 9d was identified as a tubulin inhibitor targeting colchicine binding site with an IC value of 3.4 µM. Compound 9d could strongly suppress the tubulin polymerization in Kyse450 cells. The results of molecular docking also suggested compound 9d could tightly bind into the colchicine binding site of β-tubulin. Besides, compound 9d inhibited the growth of KYSE450 cells in time and dose-dependent manners. All the results suggest that the indoline derivatives might be a class of novel tubulin inhibitors with potential anticancer activity and is worthy of further study.
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http://dx.doi.org/10.1016/j.bmcl.2021.128131DOI Listing
August 2021

Discovery of indoline derivatives as anticancer agents via inhibition of tubulin polymerization.

Bioorg Med Chem Lett 2021 Jul 11;43:128095. Epub 2021 May 11.

School of Basic Medical Sciences, Zhengzhou University Zhengzhou 450001, China. Electronic address:

Human esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers in human digestive system. It is necessary to discover novel antitumor agents for the treatment of esophageal cancers because of its poor prognosis. Indoline has been reported as an efficient anticancer fragment to design novel anticancer agents. In this work, indoline derivatives were designed, synthesized and explored their anticancer activity. Compound 9d, which exhibited potent antiproliferative activity with IC values of 1.84 μM (MGC-803 cells), 6.82 μM (A549 cells), 1.61 μM (Kyse30 cells), 1.49 μM (Kyse450 cells), 2.08 μM (Kyse510 cells) and 2.24 μM (EC-109 cells), respectively. The most active compound 9d was identified as a tubulin inhibitor targeting colchicine binding site with an IC value of 3.4 µM. Compound 9d could strongly suppress the tubulin polymerization in Kyse450 cells. The results of molecular docking also suggested compound 9d could tightly bind into the colchicine binding site of tubulin. Besides, compound 9d inhibited the growth of KYSE450 cells in a time and dose-dependent manner. All the results suggest that the indoline derivatives may be a class of novel tubulin inhibitors with potential anticancer activity, and which is worthy of further study.
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http://dx.doi.org/10.1016/j.bmcl.2021.128095DOI Listing
July 2021
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