refametinib (BAY86-9766) / AstraZeneca - LARVOL DELTA

Assessment of Genotoxic, Oxidative Stress and Histopathological Effects of Azo Dye Acid Red 119 on Blood and Gill of Freshwater Fish Channa punctata. (PubMed, J Biochem Mol Toxicol) - "Histopathological analysis further showed gill tissue damage, including aneurism, epithelial lifting, vacuolization, and fusion of secondary lamellae. Taken together, these findings demonstrated that AR 119 exerts marked genotoxic and oxidative stress in C. punctata, underscoring the urgent need for stricter effluent regulation and sustainable treatment strategies in textile industries."

Journal

Structural and Biophysical Analyses of Human MEK2 in Complex with Two Inhibitors Reveal the Determinants of Isoform-Dependent Inhibitor Binding. (PubMed, Int J Mol Sci) - "Here, we present crystal structures of human MEK2 in complex with the noncompetitive inhibitor U0126 and the allosteric inhibitor refametinib at resolutions of 3.15 Å and 3.30 Å, respectively...Molecular dynamics simulations supported these findings by revealing isoform-specific differences in oligomeric state-dependent flexibility and inhibitor-induced dynamics. Collectively, our findings define the structural basis underlying the differential inhibitor recognition of MEK2 and MEK1, providing mechanistic insight into isoform-selective MEK-targeted drug design."

Journal • MAP2K1 • MAP2K2

Single-cell multi-omics dissection of RevitalAge Markers uncovers age-dependent immunotherapy resistance and druggable targets in melanoma. (PubMed, Biol Direct) - "Drug sensitivity profiling revealed ST3GAL4 exhibited strong correlations with AZ628 (pan-RAF inhibitor) and RDEA119 (MEK inhibitor), which was further validated by molecular docking showing excellent binding affinities (binding energies: -8.7 and - 7.2 kcal/mol). This study provides structural evidence for targeted therapeutic strategies in ST3GAL4-overexpressing melanoma and establishes foundations for age-stratified immunotherapy."

IO biomarker • Journal • Melanoma • Oncology • Solid Tumor • FDFT1 • GPR143 • IRF8

Systematic pan-cancer analysis reveals the prognostic and immunological roles of ectonucleoside triphosphate diphosphohydrolase 6. (PubMed, World J Clin Oncol) - "This pan-cancer study elucidates the pivotal role of ENTPD6 in tumor progression and establishes its potential as a therapeutic target for immunotherapeutic approaches in specific malignancies."

IO biomarker • Journal • Pan tumor • Tumor mutational burden • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Microsatellite Instability • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Rectal Adenocarcinoma • Solid Tumor • MSI • TMB

Evaluation of Hepatotoxic effects of azo dye Acid Red 119 in freshwater fish Channa punctata. (PubMed, Drug Chem Toxicol) - "Histopathological examination of liver tissues revealed distinct structural anomalies (sinusoid dilation, erythrocytic infiltration, congested portal vein, vacuolization) in exposed fish. Overall, the findings indicate that AR 119 induced genotoxic effects in Channa punctata, potentially mediated by oxidative stress mechanisms."

Journal

SINGLE CELL SEQUENCING ENABLES LINEAGE-INFORMED TARGETING OF OSTEOSARCOMA (CTOS 2025) - "Stem-like lines were differentially sensitive to refametinib (IC50 range: 1.37 - 66.0 µM), a MEK inhibitor, consistent with MAPK pathway dependence. Our single-cell atlas offers a foundation for lineage-specific therapeutic targeting and disease monitoring. Expanded drug screening and larger-scale in vivo validation studies are needed to inform future precision strategies in OS."

Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Glucokinase Regulatory Protein (GCKR) Links Metabolic Reprogramming With Immune Exclusion: Insights From a Pan-Cancer Analysis and Gastric Cancer Validation. (PubMed, Hum Mutat) - "Clinically, low GCKR expression predicted poorer survival and reduced immunotherapy benefit, while higher expression indicated selective sensitivity to MEK inhibitors including refametinib and PD0325901. These findings define GCKR as both a mutation- and expression-driven biomarker that connects metabolic regulation with immune remodeling, offering translational value for prognosis and precision therapy in gastric cancer."

IO biomarker • Journal • Pan tumor • Breast Cancer • Endometrial Cancer • Gastric Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor • Uterine Cancer • BRCA

ERK/MAPK, RTK, ABL, and WNT signaling pathways as potential therapeutic targets in undifferentiated pleomorphic sarcoma (ESMO 2025) - "Table: 2713P Vulnerable signaling pathways in UPS-like sarcomas and potential drugs targeting them Drug Target Signaling pathway Pazopanib ∗∗ VEGFR, PDGFRA, PDGFRB, KIT RTK Midostaurin ∗ KIT, VEGFR2, PDGFR, FLT3 Refametinib ∗∗ MAP2K1/2 ERK/MAPK Trametinib ∗ CMK ∗ RSK2 Dasatinib ∗ BCR-ABL, SRC, KIT, PDGFR ABL WH-4-023 ∗ SRC, ABL CHIR99021 ∗ GSK3B WNT/β-catenin ∗p_adj< 0.1 ∗∗p_adj<0.05 Conclusions Our findings indicate that compounds targeting RTK/RAS/RAF/MEK, ABL, and WNT signaling pathways may yield promising treatment outcomes for patients with UPS-like tumours. Legal entity responsible for the study BostonGene Corporation."

Fibrosarcoma • Liposarcoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • Undifferentiated Pleomorphic Sarcoma • ABL1 • BCR • CTNNB1 • FLT3 • KDR • MAP2K1 • PDGFRA • PDGFRB • RPS6KA3

Identification of key ferroptosis-related genes associated with the development of gastric cancer: Prognostic models, molecular mechanisms and potential treatment strategies. (PubMed, Oncol Lett) - "Finally, using the Genomics of Drug Sensitivity in Cancer and Cancer Therapeutics Response Portal databases, potential drugs [(5Z)-7-oxozeaenol, selumetinib, RDEA119, AZ628, dabrafenib and trametinib] were identified based on the aforementioned seven key carcinogenic genes, focusing on those that targeted multiple genes. In conclusion, the present study identified 14 key ferroptosis-related genes, and seven key carcinogenic genes, which represent promising novel molecular targets for the prognosis and treatment of GC."

Journal • Gastric Adenocarcinoma • Gastric Cancer • Oncology • Solid Tumor • AKR1C2 • GABARAP • GABARAPL2 • GJA1 • MIR484 • MIR675 • NOX4 • NOX5

Activated cancer-associated fibroblasts correlate with poor survival and decreased lymphocyte infiltration in infiltrative type distal cholangiocarcinoma. (PubMed, Sci Rep) - "In vitro drug screening revealed that refametinib suppressed the growth of DBD carcinoma cells expressing high levels of fibroblast activation protein-α. In conclusion, integration of machine learning and systems biology analyses identifies aCAFs as potential biomarkers for risk stratification and therapeutic targeting in DBD cancer."

Biomarker • Journal • Biliary Cancer • Cholangiocarcinoma • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Oncology • Solid Tumor • CAFs

Drug sensitivity patterns across FAB subtypes and molecular mutations in AML. (ASCO 2025) - "M1 samples (n=22 patients) demonstrated higher sensitivity to Navitoclax (σsDSS = 15.89), while combinations with mTOR inhibitors like Navitoclax + PF-04691502 (σsDSS = 13.97) and Navitoclax + Vistusertib (σsDSS = 13.72) showed promise...M4 subtypes (n=2 patients) were most sensitive to BAY 87-2243 (σsDSS = 15.98), with dual combinations like BAY 87-2243 + Cerdulatinib (σsDSS = 14.21) and BAY 87-2243 + Pevonedistat (σsDSS = 14.13) maintaining strong responses...In M4 eos (n=9 patients), Pimasertib demonstrated notable effectiveness (σsDSS = 14.43), with dual-agent combination such as Pimasertib + SCH772984 (σsDSS = 14.24) supporting RAS/ERK pathway inhibition. Despite rare M4/M5 subtypes (n=2 patients) showing limited Refametinib sensitivity (σsDSS = 8.75), their minimal sample size precludes definitive conclusions...Likewise, mutation analysis revealed that NPM1-mutated samples showed increased sensitivity to Venetoclax (σsDSS = 13.28) and PF-04691502 (σsDSS =..."

Acute Myelogenous Leukemia • FLT3 • NPM1

Targeting the phosphatidylinositol-3-kinase (PI3K) and mitogen activated protein kinase (MAPK) signalling pathways to enhance chemoradiotherapy in locally advanced rectal cancer. (PubMed, Cancer Treat Res Commun) - "A panel of colorectal cancer (CRC) cell lines (n = 10) with varying PI3K and MAPK mutational backgrounds were treated with combinations of 5-Flourouracil (5-FU), radiation, the PI3K inhibitor copanlisib, and/or the MEK inhibitor refametinib, and their effects on proliferation in vitro were measured...Our results suggest that activation of the kinase signalling pathway may modulate PI3K/MEK inhibitor responsiveness in colorectal cancer. Furthermore, the addition of copanlisib to 5-FU chemoradiotherapy resulted in an enhanced anti-proliferative cytotoxic effect compared to 5-FU chemoradiotherapy alone, regardless of the background mutational status, and supports further clinical development of this regimen."

Journal • Colorectal Cancer • Oncology • Rectal Cancer • Solid Tumor • KRAS • PIK3CA

Bioinformatics screened of biomarkers for the prognosis of hepatocellular carcinoma. (PubMed, Cancer Biomark) - "Hub genes were enriched in various cell types. Trametinib, selumetinib, RDEA119, and teniposide were identified as potential drugs for LIHC treatment.ConclusionCDC20, TOP2A, CDK1, CAT, TAT, and FTCD may contribute to LIHC development and serve as novel prognostic biomarkers."

Biomarker • Journal • Hepatocellular Cancer • Oncology • Solid Tumor • CDC20 • CDK1 • FTCD • TOP2A

The role of SEC14L4 in esophageal squamous cell cancer: insights into clinical relevance and molecular pathways. (PubMed, Transl Cancer Res) - "Drug sensitivity analysis indicated the association of SEC14L4 expression with sensitivity of ESCC to the common chemotherapy drugs AICAR, BMS.708163, GNF.2, Nutlin.3a, PD.0325901, and RDEA119. Verification of the high expression of SEC14L4 in KYSE520 and KYSE150 was conducted, thereby confirming the study's findings. High expression of SEC14L4 is associated with poorer clinical outcomes, highlighting its potential as a therapeutic target and suggesting its involvement in the molecular mechanisms underlying ESCC."

Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma

Establishment of prognosis model of hepatocellular carcinoma based on prognosis related gene analysis and study on gene regulation mechanism of model. (PubMed, Heliyon) - "In addition, the high expression of model gene produced drug resistance to trametinib, selumetinib and RDEA119 (refametinib). The prognostic risk model based on six prognostic related DEGs is an independent prognostic factor of HCC, which can effectively predict the survival and prognosis of HCC patients."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • BUB1 • CCNA2 • CCNB1 • CDC20 • CDK1 • TOP2A

Phase I-IV Drug Trials on Hepatocellular Carcinoma in Asian Populations: A Systematic Review of Ten Years of Studies. (PubMed, Int J Mol Sci) - "Eighteen studies compared the efficacy of sorafenib with that of other drugs, including lenvatinib, cabozantinib, tepotinib, tigatuzumab, linifanib, erlotinib, resminostat, brivanib, tislelizumab, selumetinib, and refametinib. This study provides comprehensive insights into effective treatment interventions for HCC in Asian populations. The overall assessment indicates that sorafenib, used alone or in combination with atezolizumab and bevacizumab, has been the first treatment choice in the past decade to achieve better outcomes in patients with HCC in Asian populations."

Journal • Review • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • Transplantation

A practical approach to demonstrate the circular economy in remediation of textile dyes using nutraceutical industrial spent. (PubMed, RSC Adv) - "We used Nutraceutical Industrial Coriander Seed Spent (NICSS), a readily available, cheap, eco-friendly, and ready-to-use material, as an innovative adsorbent for the bioremediation of a bisazo Acid Red 119 (AR 119) dye, which is likely a mutagen from textile industrial effluents (TIE)...Utilizing plastic trash, the dye-adsorbed NICSS that was recovered as "sludge" was utilized as a reinforcing material to create composites. Dye-adsorbed NICSS thermoplastic and thermoset composites were studied and compared with NICSS composites in terms of their physicomechanical and chemical properties."

Journal

Comprehensive analysis of CPNE1 predicts prognosis and drug resistance in gastric adenocarcinoma. (PubMed, Am J Transl Res) - "CPNE1 could be a predictive biomarker and a potential target for biological therapy in STAD."

Journal • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CPNE1

DNA hypomethylation patterns and their impact on the tumor microenvironment in colorectal cancer. (PubMed, Cell Oncol (Dordr)) - "This study unveils a novel epigenetic phenotype in CRC linked to resistance against immune checkpoint inhibitors, presenting a significant step toward personalized medicine by suggesting epigenetic classifications as a means to identify ideal candidates for immunotherapy in CRC. Our findings also highlight potential therapeutic agents for the DMP subtype, offering new avenues for tailored CRC treatment strategies."

Biomarker • IO biomarker • Journal • Tumor microenvironment • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

In Silico Identification of Therapeutic Targets and Novel Drug Candidates for Malignant Peripheral Nerve Sheath Tumors. (PubMed, Front Biosci (Landmark Ed)) - "Overall, our results describe the importance of Twist1 in MPNST pathogenesis. Everolimus was also found to be a potential therapeutic drug for MPNSTs."

Journal • Brain Cancer • Fibrosis • Neurofibromatosis • Neurofibrosarcoma • Oncology • Sarcoma • Solid Tumor • TWIST1

Establishment and characterization of human organoids derived from medullary cancer and serrated adencocarcinoma; rare histological variants of colorectal cancer (EACR 2023) - "The ClinXPro-Report revealed a potential sensitivity of the different organoids to drugs such as the ERK1/ERK2 inhibitor Ulixertinib, the PI3K inhibitor Pilaralisib, the MEK inhibitor Refametinib or the S6K1 inhibitor PF-4708671.ConclusionCRC-PDOs can be used as tools to model different histological subtypes of CRC. Notably, the less frequent subtypes SAC and MC exhibited, in our analysis, significantly greater differences in gene expression compared to CCs. Our results suggest that further characterization of less frequent subtypes is necessary and that PDOs can have potential implications in the development of personalized therapies."

Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • KRAS • MAPK1 • NRAS

Identification of a novel circRNA-miRNA-mRNA regulatory axis in hepatocellular carcinoma based on bioinformatics analysis. (PubMed, Sci Rep) - "The results suggest that the sensitivity toward trametinib, refametinib (RDEA119), and selumetinib correlates to the expression of WDR76. ROC analysis showed that the area under the curve (AUC) of all genes in the regulatory axis was greater than 0.7. The identified hsa_circ_0000417/hsa_circ_0002688/hsa_circ_0001387--hsa-miR-199a-5p--WDR76 regulatory axis may provide new insights into the progression, clinical diagnosis, and treatment of HCC."

IO biomarker • Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Immune Modulation • Liver Cancer • Oncology • Solid Tumor • ACTG1 • E2F3 • MIR199A • MIR199A1 • NORE1A

Receptor Tyrosine Kinase dependent PI3K activation is an escape mechanism to vertical suppression of the EGFR/RAS/MAPK pathway in KRAS-mutated colorectal cancer cell lines. (ESMO 2018) - "... We generated four different KRAS mutated CRC cell lines (HCT15, HCT116, LoVo, SW480) resistant to a combination of cetuximab (anti-EGFR antibody) and refametinib (BAY86-9766, selective MEK-inhibitor) after continuous exposure to increasing concentration of the drugs...Either selective knockdown of these RTKs or treatment with the pan-HER inhibitor afatinib (BIBW2992) failed to revert the resistance phenotype in our cellular model, while treatment with pictilisib (GDC-0941, selective PI3Kα inhibitor) was able to restore the sensitivity to the drug combination... Our in vitro preliminary data demonstrate that PI3K activation plays a central role in the acquired resistance to the combination of anti-EGFR and MEK-i in KRAS mutated colorectal cancer cell lines. PI3K activation is achieved through concurrent activation of multiple RTKs such as HER2, HER3 and IGF1R, suggesting a cooperative mechanism."

Preclinical • Colorectal Cancer

Integrated analysis of pivotal biomarker of LSM1, immune cell infiltration and therapeutic drugs in breast cancer. (PubMed, J Cell Mol Med) - "Most importantly, pharmacogenetic analysis of BRCA cell lines revealed that LSM1 inactivation was associated with increased sensitivity to refametinib and trametinib. However, both drugs could mimic the effects of LSM1 inhibition and their drug sensitivity was associated with MEK molecules. Therefore, we investigated the clinical application of LSM1 to provide a basis for sensitive diagnosis, prognosis and targeted treatment of breast cancer."

Biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • BRCA

Integrated analysis of pivotal biomarker, immune cell infiltration, and therapeutic drugs for LSM1-mutated in breast cancer. (ASCO 2022) - "Most importantly, pharmacogenetic analysis of BRCA cell lines revealed that LSM1 inactivation was associated with increased sensitivity to refametinib, and trametinib. In brief, our finding may contribute to increasing currently limited prognostic biomarkers and treatment options for breast cancer."

Biomarker • Breast Cancer • Oncology • Solid Tumor • BRCA