ArticleACS medicinal chemistry letters2015
Optimization of a Dibenzodiazepine Hit to a Potent and Selective Allosteric PAK1 Inhibitor.
Article in ACS medicinal chemistry letters, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- p21-Activated Kinase (PAK) Group I-Targeting Inhibitors Promote the Dimeric Conformation in Live Cells.ACS chemical biology · 2026Article
- PAK1 activation drives divergent resistance mechanisms to aromatase inhibition and tamoxifen in a luminal: A breast cancer model.Molecular oncology · 2026Article
- Development of NanoBRET cellular target engagement assays in primary neurons for activating mutants of p21-activated kinase 1.bioRxiv : the preprint server for biology · 2026Article
- PAK1 inhibitor NVS-PAK1-1 preserves dendritic spines in amyloid/tau exposed neurons and 5xFAD mice.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- PAK1 regulates oligodendroglial proliferation and repopulation in homeostatic and demyelinating brain.Cellular and molecular life sciences : CMLS · 2025Article
- A role for class I p21-activated kinases in the regulation of the excitability of the actin cytoskeleton.Journal of cell science · 2025Article
- The Role of the p21-Activated Kinase Family in Tumor Immunity.International journal of molecular sciences · 2025Review
- Targeting PAK1 is effective against cutaneous squamous cell carcinoma in a syngenic mouse model.Cancer science · 2024Article
- [Computer-aided prediction and molecular mechanism investigation of active components in compound Kushen injection inhibiting p21-activated kinase 1].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2024Article
- PAK1 and Therapy Resistance in Melanoma.Cells · 2023Review
- Pak1 pathway hyper-activation mediates resistance to endocrine therapy and CDK4/6 inhibitors in ER+ breast cancer.NPJ breast cancer · 2023Article
- Review
- Article
- Development and Utility of a PAK1-Selective Degrader.Journal of medicinal chemistry · 2022Article
- Therapeutic Targeting the Allosteric Cysteinome of RAS and Kinase Families.Journal of molecular biology · 2022Review
- Group I PAKs in myelin formation and repair of the central nervous system: what, when, and how.Biological reviews of the Cambridge Philosophical Society · 2022Review
- The protein kinase CK1: Inhibition, activation, and possible allosteric modulation.Frontiers in molecular biosciences · 2022Review
- Trends in kinase drug discovery: targets, indications and inhibitor design.Nature reviews. Drug discovery · 2021Review
- Molecular modelling approaches predicted 1,2,3-triazolyl ester of ketorolac (15K) to be a novel allosteric modulator of the oncogenic kinase PAK1.Scientific reports · 2021Article
- Neuroprotective Effects of 2-Substituted 1, 3-Selenazole Amide Derivatives on Amyloid-Beta-Induced Toxicity in a Transgenic Caenorhabditis Elegans Model of Alzheimer's Disease.Neurotoxicity research · 2021Article
Corrections and comments
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Authors and funding
26 authors.
Funding
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Abstract
The discovery of inhibitors targeting novel allosteric kinase sites is very challenging. Such compounds, however, once identified could offer exquisite levels of selectivity across the kinome. Herein we report our structure-based optimization strategy of a dibenzodiazepine hit 1, discovered in a fragment-based screen, yielding highly potent and selective inhibitors of PAK1 such as 2 and 3. Compound 2 was cocrystallized with PAK1 to confirm binding to an allosteric site and to reveal novel key interactions. Compound 3 modulated PAK1 at the cellular level and due to its selectivity enabled valuable research to interrogate biological functions of the PAK1 kinase.
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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.