ArticleJournal of medicinal chemistry2015
Small-Molecule Allosteric Modulators of the Protein Kinase PDK1 from Structure-Based Docking.
Article in Journal of medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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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
15 citing papers in PubMed, 36 citations in OpenAlex.
- Phosphoinositide-dependent kinase 1 (PDK1) in cancer: molecular insights and therapeutic strategies.Frontiers in chemistry · 2026Review
- Uncovering the Role of Distal Regions in PDK1 Allosteric Activation.ACS bio & med chem Au · 2025Article
- Capturing Autoinhibited PDK1 Reveals the Linker's Regulatory Role, Informing Innovative Inhibitor Design.Journal of chemical information and modeling · 2024Article
- The value of protein allostery in rational anticancer drug design: an update.Expert opinion on drug discovery · 2024Review
- Structure-based drug design and molecular dynamics studies of an allosteric modulator targeting the protein-protein interaction site of PDK1.Journal of molecular modeling · 2024Article
- A Comprehensive Survey of Prospective Structure-Based Virtual Screening for Early Drug Discovery in the Past Fifteen Years.International journal of molecular sciences · 2022Review
- Indoprofen prevents muscle wasting in aged mice through activation of PDK1/AKT pathway.Journal of cachexia, sarcopenia and muscle · 2020Article
- A computational approach yields selective inhibitors of human excitatory amino acid transporter 2 (EAAT2).The Journal of biological chemistry · 2020Article
- The chemical diversity and structure-based discovery of allosteric modulators for the PIF-pocket of protein kinase PDK1.Journal of enzyme inhibition and medicinal chemistry · 2019Review
- Review
- p38α Mitogen-Activated Protein Kinase Is a Druggable Target in Pancreatic Adenocarcinoma.Frontiers in oncology · 2019Article
- Article
- The Development of Target-Specific Pose Filter Ensembles To Boost Ligand Enrichment for Structure-Based Virtual Screening.Journal of chemical information and modeling · 2017Article
- Structure-based discovery of potentially active semiochemicals for Cydia pomonella (L.).Scientific reports · 2016Article
- Docking Screens for Novel Ligands Conferring New Biology.Journal of medicinal chemistry · 2016Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Finding small molecules that target allosteric sites remains a grand challenge for ligand discovery. In the protein kinase field, only a handful of highly selective allosteric modulators have been found. Thus, more general methods are needed to discover allosteric modulators for additional kinases. Here, we use virtual screening against an ensemble of both crystal structures and comparative models to identify ligands for an allosteric peptide-binding site on the protein kinase PDK1 (the PIF pocket). We optimized these ligands through an analog-by-catalog search that yielded compound 4, which binds to PDK1 with 8 μM affinity. We confirmed the docking poses by determining a crystal structure of PDK1 in complex with 4. Because the PIF pocket appears to be a recurring structural feature of the kinase fold, known generally as the helix αC patch, this approach may enable the discovery of allosteric modulators for other kinases.
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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.