ArticleACS medicinal chemistry letters2021
Fragment-Based Discovery of Novel Allosteric MEK1 Binders.
Article in ACS medicinal chemistry letters, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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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
12 citing papers in PubMed, 18 citations in OpenAlex.
- Chromones as Nonclassical Inhibitors of Carbonic Anhydrase IX and XII Isoforms: Probing Chromone-Based Derivatives.Archiv der Pharmazie · 2026Article
- Epoxy tetrahydrophthalimides as potential bioactive agents: synthesis and computational study.Pest management science · 2025Article
- The identification of functional regions of MEK1 using CRISPR tiling screens.Communications biology · 2025Article
- Decoding allosteric landscapes: computational methodologies for enzyme modulation and drug discovery.RSC chemical biology · 2025Review
- Article
- Integrating fragment-based screening with targeted protein degradation and genetic rescue to explore eIF4E function.Nature communications · 2024Article
- Development of Allosteric NIK Ligands from Fragment-Based NMR Screening.ACS medicinal chemistry letters · 2023Article
- Analysis of the ERK Pathway Cysteinome for Targeted Covalent Inhibition of RAF and MEK Kinases.Journal of chemical information and modeling · 2023Article
- GSK-3β Allosteric Inhibition: A Dead End or a New Pharmacological Frontier?International journal of molecular sciences · 2023Review
- Exiting the tunnel of uncertainty: crystal soak to validated hit.Acta crystallographica. Section D, Structural biology · 2022Article
- Identification of Novel GSK-3β Hits Using Competitive Biophysical Assays.International journal of molecular sciences · 2022Article
- Recent applications of computational methods to allosteric drug discovery.Frontiers in molecular biosciences · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The MEK1 kinase plays a critical role in key cellular processes, and as such, its dysfunction is strongly linked to several human diseases, particularly cancer. MEK1 has consequently received considerable attention as a drug target, and a significant number of small-molecule inhibitors of this kinase have been reported. The majority of these inhibitors target an allosteric pocket proximal to the ATP binding site which has proven to be highly druggable, with four allosteric MEK1 inhibitors approved to date. Despite the significant attention that the MEK1 allosteric site has received, chemotypes which have been shown structurally to bind to this site are limited. With the aim of discovering novel allosteric MEK1 inhibitors using a fragment-based approach, we report here a screening method which resulted in the discovery of multiple allosteric MEK1 binders, one series of which was optimized to sub-μM affinity for MEK1 with promising physicochemical and ADMET properties.
Identifiers
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.