ReviewChemical Society reviews2016
Drugging Ras GTPase: a comprehensive mechanistic and signaling structural view.
Review in Chemical Society reviews, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
104 citing papers in PubMed, 186 citations in OpenAlex.
- Clinical utility of PDX cohorts to reveal biomarkers of intrinsic resistance and clonal architecture changes underlying acquired resistance to cetuximab in HNSCC.Signal transduction and targeted therapy · 2022Trial
- Integrated Structural and Dynamic Analysis Reveals Destabilizing Effects of KRAS Missense Variants Associated with Lung Cancer.The protein journal · 2026Article
- Phage Display Driven Identification and Computational Mapping of Macrocyclic Peptides Targeting RhoA G17V.Biochemistry · 2026Article
- Article
- From quiescence to hypertrophy: existing and emerging genetic targets to fine-tune myogenesis in cultivated muscle.Frontiers in bioengineering and biotechnology · 2026Review
- Phosphorylation induces altered protonation states and allosterically regulates Rac1-RhoGDI complex.Protein science : a publication of the Protein Society · 2026Article
- A 3' UTR polymorphism g.1618 G > A in the MAFA gene modulates miR-3678-3p binding and enhances meat production in sheep via the MAFA/GHR/JAK2 pathway.Genetics, selection, evolution : GSE · 2025Article
- Structural mechanism of mRNA decoding by mammalian GTPase GTPBP1.Nature communications · 2025Article
- Structural mechanism of mRNA decoding by mammalian GTPase GTPBP1.bioRxiv : the preprint server for biology · 2025Article
- Exploring binding and allosteric energy landscapes for the KRAS interactions with effector proteins using Markov state modeling of conformational ensembles and allosteric network modeling.Protein science : a publication of the Protein Society · 2025Review
- Article
- Pioneer in Molecular Biology: Conformational Ensembles in Molecular Recognition, Allostery, and Cell Function.Journal of molecular biology · 2025Review
- Molecular Mechanisms in the Carcinogenesis of Oral Squamous Cell Carcinoma: A Literature Review.Biomolecules · 2025Review
- In Silico Identification of Putative Allosteric Pockets and Inhibitors for the KRASG13D-SOS1 Complex in Cancer Therapy.International journal of molecular sciences · 2025Article
- Distinct association of HRAS and KRAS with MnMagnetic resonance letters · 2025Article
- Development of potent inhibitors against KRAS, its mutant G12R, allosteric and Switch-I/Switch-II site.In silico pharmacology · 2025Article
- Analysis of Pan-Specific Inhibitors of Oncogenic Mutant Forms of KRAS GTPase.Current medicinal chemistry · 2025Review
- Multiscale calculations reveal new insights into the reaction mechanism between KRASComputational and structural biotechnology journal · 2024Article
- A comprehensive review of computational cell cycle models in guiding cancer treatment strategies.NPJ systems biology and applications · 2024Review
- Molecular Mechanism of Phosphorylation-Mediated Impacts on the Conformation Dynamics of GTP-Bound KRAS Probed by GaMD Trajectory-Based Deep Learning.Molecules (Basel, Switzerland) · 2024Article
44 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 5 institutions in 4 countries.
Funding
Abstract
Ras proteins are small GTPases, cycling between inactive GDP-bound and active GTP-bound states. Through these switches they regulate signaling that controls cell growth and proliferation. Activating Ras mutations are associated with approximately 30% of human cancers, which are frequently resistant to standard therapies. Over the past few years, structural biology and in silico drug design, coupled with improved screening technology, led to a handful of promising inhibitors, raising the possibility of drugging Ras proteins. At the same time, the invariable emergence of drug resistance argues for the critical importance of additionally honing in on signaling pathways which are likely to be involved. Here we overview current advances in Ras structural knowledge, including the conformational dynamic of full-length Ras in solution and at the membrane, therapeutic inhibition of Ras activity by targeting its active site, allosteric sites, and Ras-effector protein-protein interfaces, Ras dimers, the K-Ras4B/calmodulin/PI3Kα trimer, and targeting Ras with siRNA. To mitigate drug resistance, we propose signaling pathways that can be co-targeted along with Ras and explain why. These include pathways leading to the expression (or activation) of YAP1 and c-Myc. We postulate that these and Ras signaling pathways, MAPK/ERK and PI3K/Akt/mTOR, act independently and in corresponding ways in cell cycle control. The structural data are instrumental in the discovery and development of Ras inhibitors for treating RAS-driven cancers. Together with the signaling blueprints through which drug resistance can evolve, this review provides a comprehensive and innovative master plan for tackling mutant Ras proteins.
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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.