Drug Discovery Targeting the MAPK-ERK Pathway

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (5 July 2023) | Viewed by 2242

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Guest Editor
1. Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
2. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
Interests: natural products; signal transduction; cancer; reproduction
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Special Issue Information

Dear Colleagues,

Drug discovery of targeting the mitogen-activated protein kinase (MAPK) pathway has been implicated in various diseases, including cancer treatment, neurological diseases, inflammatory disorders, etc. Members of the MAPK pathway are constituted by serine/threonine kinases that involve multiple cell responses, such as gene expression, cell growth, differentiation, development, and cell death. The MAPK pathway can be stimulated or attenuated by extracellular stimuli and/or intracellular signaling cross-talk effects. There is no doubt that ERK1 and ERK2 are major cell signals that promote many types of cancer growth. Many inhibitors in this pathway have been approved and clinically evaluated; however, the response rates and prognosis of patients are still very low. This Special Issue welcomes any manuscripts or reviews dedicated to the study of drug resistance, dosage use in targeted therapy and combination treatments to modulate this pathway.

Dr. Yung-Chia Chen
Guest Editor

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Keywords

  • MAPK
  • ERK
  • JNK
  • tyrosine kinase
  • cancer
  • cell growth

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Published Papers (1 paper)

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Research

15 pages, 2717 KiB  
Article
The MEK Inhibitor Trametinib Improves Outcomes following Subarachnoid Haemorrhage in Female Rats
by Jesper Peter Bömers, Anne-Sofie Grell, Lars Edvinsson, Sara Ellinor Johansson and Kristian Agmund Haanes
Pharmaceuticals 2022, 15(12), 1446; https://doi.org/10.3390/ph15121446 - 22 Nov 2022
Cited by 3 | Viewed by 1687
Abstract
Aneurysmal subarachnoid haemorrhage (SAH) is a haemorrhagic stroke that causes approximately 5% of all stroke incidents. We have been working on a treatment strategy that targets changes in cerebrovascular contractile receptors, by blocking the MEK/ERK1/2 signalling pathway. Recently, a positive effect of trametinib [...] Read more.
Aneurysmal subarachnoid haemorrhage (SAH) is a haemorrhagic stroke that causes approximately 5% of all stroke incidents. We have been working on a treatment strategy that targets changes in cerebrovascular contractile receptors, by blocking the MEK/ERK1/2 signalling pathway. Recently, a positive effect of trametinib was found in male rats, but investigations of both sexes in pre-clinical studies are an important necessity. In the current study, a SAH was induced in female rats, by autologous blood-injection into the pre-chiasmatic cistern. This produces a dramatic, transient increase in intracranial pressure (ICP) and an acute and prolonged decrease in cerebral blood flow. Rats were then treated with either vehicle or three doses of 0.5 mg/kg trametinib (specific MEK/ERK1/2 inhibitor) intraperitoneally at 3, 9, and 24 h after the SAH. The outcome was assessed by a panel of tests, including intracranial pressure (ICP), sensorimotor tests, a neurological outcome score, and myography. We observed a significant difference in arterial contractility and a reduction in subacute increases in ICP when the rats were treated with trametinib. The sensory motor and neurological outcomes in trametinib-treated rats were significantly improved, suggesting that the improved outcome in females is similar to that of males treated with trametinib. Full article
(This article belongs to the Special Issue Drug Discovery Targeting the MAPK-ERK Pathway)
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