c-Met kinase inhibitors: an update patent review (2014-2017)

Zhang, Qingwen; Ye, Zi-Dan; Shi, Lei

doi:10.1080/13543776.2019.1552261

Cited by 23 publications

(9 citation statements)

References 20 publications

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“…Normal c-Met signaling plays a critical role in embryogenesis, liver generation [29] and wound healing [30] by regulating cell proliferation and differentiation. As a protooncogene, aberrant HGF/c-Met activation has been closely linked to the initiation and metastasis of various types of human cancers [23,[31][32][33], especially NSCLC [2,34], through the regulation multiple biological processes such as tumor proliferation, metastasis, survival and EMT [23]. Aberrantly activated c-Met signaling can arise from the mutation of c-Met, ampli cation of MET, or c-Met overexpression due to increased HGF level [23] which also mediates the acquired resistance of EGFR-TKIs such ge tinib in NSCLC.…”

Section: Discussionmentioning

confidence: 99%

Dictamnine, a Novel c-Met Inhibitor, Suppresses the Proliferation of Lung Cancer Cells by Downregulating the PI3K/Ak/mTOR and MAPK Signaling Pathways

Zhang

Peng

et al. 2020

Preprint

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Background: Dictamnine (Dic), a naturally occurring furoquinoline alkaloid isolated from the root bark of Dictamnus dasycarpus Turcz., is reported to display a wide range of potential pharmacological properties including anticancer activity against multiple cancer types. However, little is known about the direct target proteins and anticancer mechanisms of Dic.Methods: Anticancer effects of Dic and chemotherapy resistance of lung cancer were determined by CCK8, EdU and apoptosis assay. Boyden chamber migration and invasion, wound healing assay, plate colony formation and sphere formation assay were performed to explore the effects of Dic on metastasis and stemness of lung cancer cells. Protein docking analysis, cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used for prediction and confirmation of the interaction between Dic and c-Met. qRT-PCR, Western blotting and immunohistochemistry (IHC) were used in mechanism investigation. Tumor xenograft model was used to evaluate the anti-tumor effects of Dic in vivo.Results: Dic was found to suppress the proliferation of lung cancer cells and attenuate the activation of the PI3K/AKT/mTOR and mitogen-activated protein kinase (MAPK) signaling pathways by directly inhibiting the phosphorylation and activation of the receptor tyrosine kinase c-Met. Moreover, Dic treatment significantly inhibited the colony formation, migration, invasion, stemness, adhesive ability, epithelial-mesenchymal transition and in vivo xenograft tumor growth of A549 lung cancer cells. Notably, the combination of Dic and gefitinib synergistically inhibited the cell proliferation, induced apoptosis, and suppressed the PI3K/Akt/mTOR and MAPK signaling pathways in PC9 gefitinib resistant cells.Conclusions: In conclusion, Dic was identified as a novel c-Met inhibitor and our results suggest the potential use of Dic as a new therapeutic agent in the treatment of lung cancer or other cancers with overactive c-Met pathway.

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Section: Discussionmentioning

confidence: 99%

Dictamnine, a Novel c-Met Inhibitor, Suppresses the Proliferation of Lung Cancer Cells by Downregulating the PI3K/Ak/mTOR and MAPK Signaling Pathways

Zhang

Peng

et al. 2020

Preprint

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“…Both of these oncogenes were previously thought to be undruggable but nevertheless, a few inhibitors for both of them have been published in the last few years. The readers interested in the drugs designed for oncogenic kinases or other oncogenic pathways are referred to other reviews (Bhullar et al, 2018;Solassol et al, 2019;Tang and Zhao, 2019;Wang et al, 2019;Zhang et al, 2019b).…”

Section: Targeting Oncogenesmentioning

confidence: 99%

Transcription and Translation Inhibitors in Cancer Treatment

et al. 2020

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Transcription and translation are fundamental cellular processes that govern the protein production of cells. These processes are generally up regulated in cancer cells, to maintain the enhanced metabolism and proliferative state of these cells. As such cancerous cells can be susceptible to transcription and translation inhibitors. There are numerous druggable proteins involved in transcription and translation which make lucrative targets for cancer drug development. In addition to proteins, recent years have shown that the "undruggable" transcription factors and RNA molecules can also be targeted to hamper the transcription or translation in cancer. In this review, we summarize the properties and function of the transcription and translation inhibitors that have been tested and developed, focusing on the advances of the last 5 years. To complement this, we also discuss some of the recent advances in targeting oncogenes tightly controlling transcription including transcription factors and KRAS. In addition to natural and synthetic compounds, we review DNA and RNA based approaches to develop cancer drugs. Finally, we conclude with the outlook to the future of the development of transcription and translation inhibitors.

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“…MET , encoding the proto‐oncogene tyrosine kinase c‐MET, is the receptor for hepatocyte growth factor (HGF) [7, 8]. c‐MET is mainly expressed in epithelial cells, and its ligand HGF is expressed and released by surrounding mesenchymal cells [9].…”

Section: Molecular Tumor Boardmentioning

confidence: 99%

“…c‐MET is mainly expressed in epithelial cells, and its ligand HGF is expressed and released by surrounding mesenchymal cells [9]. Under normal physiological conditions, the c‐MET signaling pathway regulates multiple cellular responses, including growth, morphogenesis, apoptosis, and motility, which is very important in the control of tissue homeostasis [8–10]. Of note, MET signaling activation can stimulate some proangiogenic factors and induce angiogenesis, leading to the initiation of cancer progression [11].…”

Section: Molecular Tumor Boardmentioning

confidence: 99%

Identification of a Novel EHBP1-MET Fusion in an Intrahepatic Cholangiocarcinoma Responding to Crizotinib

Liu

et al. 2020

The Oncologist

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As an aggressive tumor, intrahepatic cholangiocarcinoma (ICC) originates in the epithelium of the bile duct and has a poor prognosis. The therapeutic options for ICC are challenging and limited because of poor response to chemotherapy and the lack of targeted therapy. Here we report on a 41-year-old female patient with ICC with EHBP1-MET fusion and multiple intrahepatic metastases responding to crizotinib. Nextgeneration sequencing-based tumor mutation profiling was performed on the tumor biopsy and circulating tumor DNA from plasma. A novel EHBP1-MET fusion was identified and

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c-Met kinase inhibitors: an update patent review (2014-2017)

Cited by 23 publications

References 20 publications

Dictamnine, a Novel c-Met Inhibitor, Suppresses the Proliferation of Lung Cancer Cells by Downregulating the PI3K/Ak/mTOR and MAPK Signaling Pathways

Dictamnine, a Novel c-Met Inhibitor, Suppresses the Proliferation of Lung Cancer Cells by Downregulating the PI3K/Ak/mTOR and MAPK Signaling Pathways

Transcription and Translation Inhibitors in Cancer Treatment

Identification of a Novel EHBP1-MET Fusion in an Intrahepatic Cholangiocarcinoma Responding to Crizotinib

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