GSK2606414: Difference between revisions

Latest revision as of 11:41, 15 February 2025

GSK2606414[edit]

GSK2606414 is a potent and selective inhibitor of the protein kinase PERK (PKR-like endoplasmic reticulum kinase), which is involved in the unfolded protein response (UPR) pathway. This compound has been studied for its potential therapeutic applications in diseases characterized by endoplasmic reticulum stress, such as neurodegenerative diseases and certain types of cancer.

Mechanism of Action[edit]

GSK2606414 functions by inhibiting the activity of PERK, a key sensor of the unfolded protein response. Under conditions of endoplasmic reticulum stress, PERK is activated and phosphorylates the eukaryotic initiation factor 2 alpha (eIF2_), leading to a reduction in general protein synthesis and an increase in the translation of specific stress-related proteins. By inhibiting PERK, GSK2606414 prevents the phosphorylation of eIF2_, thereby modulating the cellular response to stress.

Therapeutic Potential[edit]

Neurodegenerative Diseases[edit]

In neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS), the accumulation of misfolded proteins can lead to chronic ER stress and activation of the UPR. GSK2606414 has been investigated for its ability to alleviate ER stress and improve cell survival in models of these diseases.

Cancer[edit]

In certain types of cancer, the UPR is hijacked to support tumor growth and survival under stressful conditions such as hypoxia and nutrient deprivation. By inhibiting PERK, GSK2606414 may disrupt the adaptive UPR in cancer cells, leading to increased sensitivity to stress and potential cell death. This makes it a candidate for combination therapy with other anticancer agents.

Challenges and Considerations[edit]

While GSK2606414 shows promise in preclinical studies, there are challenges associated with its use. The inhibition of PERK can have widespread effects on cellular homeostasis, and careful consideration of dosing and potential side effects is necessary. Further research is needed to fully understand the implications of PERK inhibition in different disease contexts.

Related Pages[edit]

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-'''GSK2606414''' is a selective [[inhibitor]] of the [[protein kinase]] PERK, which is involved in the [[unfolded protein response]]. It has been studied for its potential use in the treatment of [[neurodegenerative diseases]] such as [[Parkinson's disease]] and [[Alzheimer's disease]].
+== GSK2606414 ==
+[[File:GSK2606414_structure.png|thumb|right|Chemical structure of GSK2606414]]
+'''GSK2606414''' is a potent and selective inhibitor of the [[protein kinase]] [[PERK]] (PKR-like endoplasmic reticulum kinase), which is involved in the [[unfolded protein response]] (UPR) pathway. This compound has been studied for its potential therapeutic applications in diseases characterized by [[endoplasmic reticulum stress]], such as [[neurodegenerative diseases]] and certain types of [[cancer]].
 == Mechanism of Action ==
-GSK2606414 works by inhibiting the protein kinase PERK. PERK is one of three major signaling pathways of the unfolded protein response (UPR), which is activated in response to the accumulation of unfolded proteins in the [[endoplasmic reticulum]] (ER). By inhibiting PERK, GSK2606414 reduces the level of ER stress and the subsequent cell death that can occur in neurodegenerative diseases.
+GSK2606414 functions by inhibiting the activity of PERK, a key sensor of the unfolded protein response. Under conditions of endoplasmic reticulum stress, PERK is activated and phosphorylates the [[eukaryotic initiation factor 2 alpha]] (eIF2_), leading to a reduction in general [[protein synthesis]] and an increase in the translation of specific stress-related proteins. By inhibiting PERK, GSK2606414 prevents the phosphorylation of eIF2_, thereby modulating the cellular response to stress.
+== Therapeutic Potential ==
+=== Neurodegenerative Diseases ===
-== Potential Therapeutic Uses ==
+In [[neurodegenerative diseases]] such as [[Alzheimer's disease]], [[Parkinson's disease]], and [[amyotrophic lateral sclerosis]] (ALS), the accumulation of misfolded proteins can lead to chronic ER stress and activation of the UPR. GSK2606414 has been investigated for its ability to alleviate ER stress and improve cell survival in models of these diseases.
-Research has suggested that GSK2606414 may have potential therapeutic uses in the treatment of neurodegenerative diseases. In preclinical studies, it has been shown to reduce the level of ER stress and cell death in neurons, suggesting that it may have neuroprotective effects.
+=== Cancer ===
-In a study on a mouse model of prion disease, treatment with GSK2606414 was found to delay the onset of clinical signs and extend survival. However, the treatment also caused side effects including weight loss and hyperglycemia.
+[[File:GSK2606414_structure.png|thumb|left|GSK2606414 has potential applications in cancer therapy.]]
-== Side Effects ==
+In certain types of cancer, the UPR is hijacked to support tumor growth and survival under stressful conditions such as hypoxia and nutrient deprivation. By inhibiting PERK, GSK2606414 may disrupt the adaptive UPR in cancer cells, leading to increased sensitivity to stress and potential cell death. This makes it a candidate for combination therapy with other anticancer agents.
-The most common side effects of GSK2606414 in preclinical studies have been weight loss and [[hyperglycemia]]. These side effects are believed to be due to the inhibition of PERK in peripheral tissues.
+== Challenges and Considerations ==
-== Future Research ==
+While GSK2606414 shows promise in preclinical studies, there are challenges associated with its use. The inhibition of PERK can have widespread effects on cellular homeostasis, and careful consideration of dosing and potential side effects is necessary. Further research is needed to fully understand the implications of PERK inhibition in different disease contexts.
-Further research is needed to determine the safety and efficacy of GSK2606414 in humans. In particular, studies are needed to determine the optimal dosing regimen and to further investigate the potential side effects.
+== Related Pages ==
+* [[Protein kinase]]
+* [[Unfolded protein response]]
+* [[Neurodegenerative diseases]]
+* [[Cancer]]
+[[Category:Pharmacology]]
 [[Category:Experimental drugs]]
-[[Category:Neurodegenerative disease drug discovery]]
-[[Category:Protein kinase inhibitors]]
-{{medicine-stub}}