ArticleJournal of medicinal chemistry2018
Discovery and Structure-Based Optimization of Benzimidazole-Derived Activators of SOS1-Mediated Nucleotide Exchange on RAS.
Article in Journal of medicinal chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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Who cites it
19 citing papers in PubMed, 53 citations in OpenAlex.
- Computational insights on the molecular interplay between KRas (G12D mutation) and SOS1 modulated by the inhibitor BI-3406.PLoS computational biology · 2026Article
- SOS1: tracking the evolving path from promising to actionable therapeutic target in RAS-dependent cancers.Molecular cancer · 2026Review
- A Computational Approach to Identify Novel Protein Targets Uncovers New Potential Mechanisms of Action of Mirtazapine S(+) and R(-) Enantiomers in Rett Syndrome.Journal of neurochemistry · 2025Article
- Drugging Challenging Cancer Targets Using Fragment-Based Methods.Chemical reviews · 2025Review
- Exploiting Solvent Exposed Salt-Bridge Interactions for the Discovery of Potent Inhibitors of SOS1 Using Free-Energy Perturbation Simulations.ACS medicinal chemistry letters · 2025Article
- Discovery of Small Molecules that Bind to Son of Sevenless 2 (SOS2).Journal of medicinal chemistry · 2025Article
- Targeted Degradation of SOS1 Exhibits Potent Anticancer Activity and Overcomes Resistance in KRAS-Mutant Tumors and BCR-ABL-Positive Leukemia.Cancer research · 2025Article
- From bench to bedside: current development and emerging trend of KRAS-targeted therapy.Acta pharmacologica Sinica · 2024Review
- Development of PROTACS degrading KRAS and SOS1.Oncology research · 2024Review
- Targeting small GTPases: emerging grasps on previously untamable targets, pioneered by KRAS.Signal transduction and targeted therapy · 2023Review
- Design, Synthesis, and Bioevaluation of Pyrido[2,3-ACS medicinal chemistry letters · 2023Article
- Development of SOS1 Inhibitor-Based Degraders to TargetJournal of medicinal chemistry · 2022Article
- Design and Discovery of MRTX0902, a Potent, Selective, Brain-Penetrant, and Orally Bioavailable Inhibitor of the SOS1:KRAS Protein-Protein Interaction.Journal of medicinal chemistry · 2022Article
- Conformations and binding pockets of HRas and its guanine nucleotide exchange factors complexes in the guanosine triphosphate exchange process.Journal of computational chemistry · 2022Article
- Discovery of a dual Ras and ARF6 inhibitor from a GPCR endocytosis screen.Nature communications · 2021Article
- Structure-based inhibitor design of mutant RAS proteins-a paradigm shift.Cancer metastasis reviews · 2020Review
- Biology, pathology, and therapeutic targeting of RAS.Advances in cancer research · 2020Review
- Structural Insights into the Regulation Mechanism of Small GTPases by GEFs.Molecules (Basel, Switzerland) · 2019Review
- Lowering Lipophilicity by Adding Carbon: AzaSpiroHeptanes, a logACS medicinal chemistry letters · 2019Article
Corrections and comments
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Authors and funding
22 authors at 2 institutions in 2 countries.
Funding
Abstract
Son of sevenless homologue 1 (SOS1) is a guanine nucleotide exchange factor that catalyzes the exchange of GDP for GTP on RAS. In its active form, GTP-bound RAS is responsible for numerous critical cellular processes. Aberrant RAS activity is involved in ∼30% of all human cancers; hence, SOS1 is an attractive therapeutic target for its role in modulating RAS activation. Here, we describe a new series of benzimidazole-derived SOS1 agonists. Using structure-guided design, we discovered small molecules that increase nucleotide exchange on RAS in vitro at submicromolar concentrations, bind to SOS1 with low double-digit nanomolar affinity, rapidly enhance cellular RAS-GTP levels, and invoke biphasic signaling changes in phosphorylation of ERK 1/2. These compounds represent the most potent series of SOS1 agonists reported to date.
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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.