ArticleCancer discovery2024
The Pan-RAF-MEK Nondegrading Molecular Glue NST-628 Is a Potent and Brain-Penetrant Inhibitor of the RAS-MAPK Pathway with Activity across Diverse RAS- and RAF-Driven Cancers.
Article in Cancer discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed.
- Practical management of BRAF inhibitors in glioma: toxicity and resistance.CNS oncology · 2026Review
- Monovalent Nondegrading Molecular Glues: An Updated Overview of Emerging Mechanisms and Therapeutic Development.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Ubiquitin family as novel protein partners for molecular glues.npj drug discovery · 2026Review
- SCGB1A1 suppresses prostate cancer proliferation and metastasis by modulating the MAPK signaling pathway.International urology and nephrology · 2026Article
- Contemporary design of small-molecule kinase modulators: orthosteric, allosteric and induced-proximity strategies.Nature reviews. Drug discovery · 2026Review
- Cryo-EM structure and biochemical characterization of a BRAF/CRAF heterodimer: Negative charge in the NtA motif is not required for RAF activation.bioRxiv : the preprint server for biology · 2026Article
- Dual RAF inhibition outperforms RAF-MEK combinations for suppressing ERK signaling in KRAS mutant cells.NPJ systems biology and applications · 2026Article
- Novel Syngeneic Cell Lines for Studying High-Risk BRAFV600E-Driven Colorectal Cancer In Vivo.Cancer research communications · 2026Article
- Review
- RAF isoform selectivity of MEK inhibitors and rational design of a covalent ARAF-MEK inhibitor.bioRxiv : the preprint server for biology · 2025Article
- Orthosteric Molecular Glue Inhibits COP9 Signalosome with Substrate-Dependent Potency.bioRxiv : the preprint server for biology · 2025Article
- Mechanisms that matter: unbiased cellular screening for degraders.npj drug discovery · 2025Review
- ZDHHC9 promotes osteosarcoma progression via KRAS-associated enhancement of the RAS/MAPK signaling pathway.Scientific reports · 2025Article
- Selective inhibition of BRAF and CRAF sensitizes NF1-deficient malignant peripheral nerve sheath tumors to MEK inhibitors.Molecular medicine (Cambridge, Mass.) · 2025Article
- The Roles of SHCBP1 in Cancer Hallmarks: Molecular Mechanisms and Therapeutic Implications.International journal of molecular sciences · 2025Review
- Cryo-EM structures of CRAF/MEK1/14-3-3 complexes in autoinhibited and open-monomer states reveal features of RAF regulation.Nature communications · 2025Article
- Construction of lactylation (LA) risk signature in prostate cancer based on 4D fast DIA L-lactated quantitative genomics.Journal of translational medicine · 2025Article
- Exploring the pathway: clinical utility and open challenges of targeting BRAF alterations in biliary tract cancers and gastrointestinal malignancies.ESMO gastrointestinal oncology · 2025Review
- Targeting MDM2, RAS, and PCNA for cancer targeted therapy: pan-cancer approaches vs. cancer-specific strategies.Frontiers in pharmacology · 2025Review
- In-cell single-molecule FRET measurement of cytosolic RAF proteins to investigate the structural states and kinetics among them.Frontiers in molecular biosciences · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors.
Funding
Abstract
Alterations in the RAS-MAPK signaling cascade are common across multiple solid tumor types and are a driver for many cancers. NST-628 is a potent pan-RAF-MEK molecular glue that prevents the phosphorylation and activation of MEK by RAF, overcoming the limitations of traditional RAS-MAPK inhibitors and leading to deep durable inhibition of the pathway. Cellular, biochemical, and structural analyses of RAF-MEK complexes show that NST-628 engages all isoforms of RAF and prevents the formation of BRAF-CRAF heterodimers, a differentiated mechanism from all current RAF inhibitors. With a potent and durable inhibition of the RAF-MEK signaling complex as well as high intrinsic permeability into the brain, NST-628 demonstrates broad efficacy in cellular and patient-derived tumor models harboring diverse MAPK pathway alterations, including orthotopic intracranial models. Given its functional and pharmacokinetic mechanisms that are differentiated from previous therapies, NST-628 is positioned to make an impact clinically in areas of unmet patient need. Significance: This study introduces NST-628, a molecular glue having differentiated mechanism and drug-like properties. NST-628 treatment leads to broad efficacy with high tolerability and central nervous system activity across multiple RAS- and RAF-driven tumor models. NST-628 has the potential to provide transformative clinical benefits as both monotherapy and vertical combination anchor.
Indexed as
Identifiers
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.