ArticleCell2024
Targeting Ras-, Rho-, and Rab-family GTPases via a conserved cryptic pocket.
Article in Cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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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.
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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
36 citing papers in PubMed.
- Decoding Biomolecular Phase Separation: From Physiological Roles to Pathological Mechanisms and Therapeutic Biomaterials Design.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Protein Language Model Embeddings Recover Evolutionary and Functional Organization Across the Ras Superfamily.Journal of molecular evolution · 2026Article
- Chemical Genetic Targeting of the LRRK2 GTPase Domain.bioRxiv : the preprint server for biology · 2026Article
- GTPase RAB31 supports ANXA1-driven macrophage education through clathrin-mediated endocytosis to suppress antitumor immunity.Journal for immunotherapy of cancer · 2026Article
- The potential and therapeutic advances of the integrin family in neurological disorders.Neural regeneration research · 2026Article
- RAB1A is a novel vulnerability in uveal melanoma revealed by dual inhibition of MNK1/2 and mTOR.Cell death and differentiation · 2026Article
- Article
- Mechanisms of Eosinophil Degranulation.Cells · 2026Review
- Rab27: Molecular switch of tumor exosome secretion (Review).International journal of molecular medicine · 2026Review
- Rho GTPases in cancer resistance: mechanisms, vulnerabilities, and therapeutic opportunities.Biochemical Society transactions · 2026Review
- DOCK1 inhibitor Box5 (TFA) suppresses proliferation of AML cell lines and prolongs survival in AML xenograft models.Scientific reports · 2026Article
- AH001: A New Drug Targeting RhoA in Heart Failure.Circulation research · 2026Article
- Activity of Direct KRAS(G12C) Inhibitors in Preclinical Models of Pediatric Cancer.Molecular cancer therapeutics · 2026Article
- Targeting "undruggable" cancer proteins: pharmacological challenges and emerging strategies.Translational cancer research · 2026Review
- ARHGAP21 enhances metastasis in hepatocellular carcinoma by inhibiting ubiquitination of filamin A.Cell death discovery · 2026Article
- Disulfide tethering reveals cryptic pockets in oncogenic KRAS.Communications chemistry · 2026Article
- De novo design of Ras isoform selective binders.Cell chemical biology · 2026Article
- Recent breakthroughs in understanding the allosteric features of Ras GTPases and their effector and regulatory protein interactions, enabling drug design.Current opinion in structural biology · 2026Review
- Cold exposure-inducedActa pharmaceutica Sinica. B · 2026Article
- RHOA at the intersection of inflammation-driven and sporadic colorectal cancer.Frontiers in immunology · 2026Review
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Authors and funding
17 authors.
Funding
Abstract
The family of Ras-like GTPases consists of over 150 different members, regulated by an even larger number of guanine exchange factors (GEFs) and GTPase-activating proteins (GAPs) that comprise cellular switch networks that govern cell motility, growth, polarity, protein trafficking, and gene expression. Efforts to develop selective small molecule probes and drugs for these proteins have been hampered by the high affinity of guanosine triphosphate (GTP) and lack of allosteric regulatory sites. This paradigm was recently challenged by the discovery of a cryptic allosteric pocket in the switch II region of K-Ras. Here, we ask whether similar pockets are present in GTPases beyond K-Ras. We systematically surveyed members of the Ras, Rho, and Rab family of GTPases and found that many GTPases exhibit targetable switch II pockets. Notable differences in the composition and conservation of key residues offer potential for the development of optimized inhibitors for many members of this previously undruggable family.
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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.