ArticleChemical biology & drug design2010
Structural determinants of PERK inhibitor potency and selectivity.
Article in Chemical biology & drug design, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- In silico analysis of PERK interactions with engineered alpha lactalbumin peptides using molecular dynamics simulations.Scientific reports · 2026Article
- Overcoming Cancer Persister Cells by Stabilizing the ATF4 Promoter G-quadruplex.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Trends in kinase drug discovery: targets, indications and inhibitor design.Nature reviews. Drug discovery · 2021Review
- PERK Pathway and Neurodegenerative Disease: To Inhibit or to Activate?Biomolecules · 2021Review
- ER Stress-Sensor Proteins and ER-Mitochondrial Crosstalk-Signaling Beyond (ER) Stress Response.Biomolecules · 2021Review
- Small molecule strategies to harness the unfolded protein response: where do we go from here?The Journal of biological chemistry · 2020Review
- Synergistic Effect of Chlorogenic Acid and Caffeic Acid with Fosfomycin on Growth Inhibition of a ResistantACS omega · 2020Article
- The Integrated Stress Response and Phosphorylated Eukaryotic Initiation Factor 2α in Neurodegeneration.Journal of neuropathology and experimental neurology · 2020Review
- Unfolded Protein Response as a Therapeutic Target in Cardiovascular Disease.Current topics in medicinal chemistry · 2019Review
- Therapeutic Opportunities in Eukaryotic Translation.Cold Spring Harbor perspectives in biology · 2018Review
- PERK activation mitigates tau pathologyEMBO molecular medicine · 2017Article
- PERK-opathies: An Endoplasmic Reticulum Stress Mechanism Underlying Neurodegeneration.Current Alzheimer research · 2016Review
- The unfolded protein response in glioblastomas: targetable or trouble?Future science OA · 2015Review
- Molecular pathways: the PERKs and pitfalls of targeting the unfolded protein response in cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Review
- Proteotoxic crisis, the ubiquitin-proteasome system, and cancer therapy.BMC biology · 2014Review
- Identification and validation of novel PERK inhibitors.Journal of chemical information and modeling · 2014Article
- ER stress-induced eIF2-alpha phosphorylation underlies sensitivity of striatal neurons to pathogenic huntingtin.PloS one · 2014Article
- Dual activators of protein kinase R (PKR) and protein kinase R-like kinase PERK identify common and divergent catalytic targets.Chembiochem : a European journal of chemical biology · 2013Article
- Specific small molecule inhibitors of Skp2-mediated p27 degradation.Chemistry & biology · 2012Article
- Bioinformatics and variability in drug response: a protein structural perspective.Journal of the Royal Society, Interface · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The unfolded protein response (UPR) is a coordinated program that promotes cell survival under conditions of endoplasmic reticulum stress and is required in tumor progression as well. To date, no specific small molecule inhibitor targeting this pathway has been identified. Pancreatic endoplasmic reticulum kinase (PERK), one of the UPR transducers, is an eIF2α kinase. Compromising PERK function inhibits tumor growth in mice, suggesting that PERK may be a cancer drug target, but identifying a specific inhibitor of any kinase is challenging. The goal of this study was to identify some pair-wise receptor-ligand atomic contacts that confer selective PERK inhibition. Compounds selectively inhibiting PERK-mediated phosphorylation in vitro were identified using an initial virtual library screen, followed by structure-activity hypothesis testing. The most potent PERK selective inhibitors utilize three specific kinase active site contacts that, when absent from chemically similar compounds, abrogates the inhibition: (i) a strong van der Waals contact with PERK residue Met7, (ii) interactions with the N-terminal portion of the activation loop, and (iii) groups providing electrostatic complementarity to Asp144. Interestingly, the activation loop contact is required for PERK selectivity to emerge. Understanding these structure-activity relationships may accelerate rational PERK inhibitor design.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.