ArticleJCI insight2018
Development of MK-8353, an orally administered ERK1/2 inhibitor, in patients with advanced solid tumors.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01358331 (A Phase 1 Study to Evaluate the Safety, Tolerability and Efficacy of MK-8353), which is not on this map. Cited by 78 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.
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.
A Phase 1 Study to Evaluate the Safety, Tolerability and Efficacy of MK-8353 (Formerly SCH 900353) in Subjects With Advanced Solid Tumors (Protocol No. 001 (Formerly P06203))
Who cites it
78 citing papers in PubMed.
- KRAS Signaling Inhibition Induces a Targetable Metabolic Dependency on Lipophagy-Dependent Fatty Acid Oxidation in Pancreatic Cancer.Cancer research · 2026Article
- Deprivation of EGFR signal causes senolysis in PDAC with CDK4/6 inhibition.Cell death and differentiation · 2026Article
- Identification of Novel Extracellular-Signal-Regulated Kinase 2 Inhibitors Through Machine Learning-Driven De Novo Design, Molecular Docking, and Free-Energy Perturbation.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Particulate matter 2.5 promotes bladder cancer cell migration and invasion through the crosstalk between integrin-mediated MAPK/ERK and Wnt/β-catenin pathways.Particle and fibre toxicology · 2026Article
- Secretory carrier membrane protein 3 modulates nuclear ERK1/2 signaling and drug response in triple-negative breast cancer.Frontiers in oncology · 2026Article
- Mimulone-induced Apoptosis through the Extrinsic Pathway and ERK Inactivation in Human Hepatoma Hep3B Cells.Cell biochemistry and biophysics · 2025Article
- Advances in ERK1/2 inhibition: a medicinal chemistry perspective on structure and regulation.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Delivery of an ERK inhibitor using bioactive lipid nanoparticles reduces angiogenesis and prevents oral squamous cell carcinoma development.Journal of nanobiotechnology · 2025Article
- The Role of ETS2 in Macrophage Inflammation.DNA and cell biology · 2025Review
- Elucidating Ras protein as a dual therapeutic target for inflammation and cancer: a review.Discover oncology · 2025Review
- A first-in-class selective inhibitor of ERK1/2 and ERK5 overcomes drug resistance with a single-molecule strategy.Signal transduction and targeted therapy · 2025Article
- Investigation ofIn silico pharmacology · 2025Article
- A phase 1b study of the ERK inhibitor MK-8353 plus pembrolizumab in patients with advanced solid tumors.Investigational new drugs · 2024Article
- Article
- Mechanism and application of feedback loops formed by mechanotransduction and histone modifications.Genes & diseases · 2024Review
- Tumor biomarkers for diagnosis, prognosis and targeted therapy.Signal transduction and targeted therapy · 2024Review
- MUC1 promotes cervical squamous cell carcinoma through ERK phosphorylation-mediated regulation of ITGA2/ITGA3.BMC cancer · 2024Article
- Molecular Targeting of the Phosphoinositide-3-Protein Kinase (PI3K) Pathway across Various Cancers.International journal of molecular sciences · 2024Review
- A novel selective ERK1/2 inhibitor, Laxiflorin B, targets EGFR mutation subtypes in non-small-cell lung cancer.Acta pharmacologica Sinica · 2024Article
- Article
18 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
28 authors.
Funding
Abstract
backgroundConstitutive activation of ERK1/2 occurs in various cancers, and its reactivation is a well-described resistance mechanism to MAPK inhibitors. ERK inhibitors may overcome the limitations of MAPK inhibitor blockade. The dual mechanism inhibitor SCH772984 has shown promising preclinical activity across various BRAFV600/RAS-mutant cancer cell lines and human cancer xenografts.
methodsWe have developed an orally bioavailable ERK inhibitor, MK-8353; conducted preclinical studies to demonstrate activity, pharmacodynamic endpoints, dosing, and schedule; completed a study in healthy volunteers (P07652); and subsequently performed a phase I clinical trial in patients with advanced solid tumors (MK-8353-001). In the P07652 study, MK-8353 was administered as a single dose in 10- to 400-mg dose cohorts, whereas in the MK-8353-001 study, MK-8353 was administered in 100- to 800-mg dose cohorts orally twice daily. Safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity were analyzed.
resultsMK-8353 exhibited comparable potency with SCH772984 across various preclinical cancer models. Forty-eight patients were enrolled in the P07652 study, and twenty-six patients were enrolled in the MK-8353-001 study. Adverse events included diarrhea (44%), fatigue (40%), nausea (32%), and rash (28%). Dose-limiting toxicity was observed in the 400-mg and 800-mg dose cohorts. Sufficient exposure to MK-8353 was noted that correlated with biological activity in preclinical data. Three of fifteen patients evaluable for treatment response in the MK-8353-001 study had partial response, all with BRAFV600-mutant melanomas.
conclusionMK-8353 was well tolerated up to 400 mg twice daily and exhibited antitumor activity in patients with BRAFV600-mutant melanoma. However, antitumor activity was not particularly correlated with pharmacodynamic parameters.
trial registrationClinicalTrials.gov NCT01358331.
fundingMerck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., and NIH (P01 CA168585 and R35 CA197633).
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