SCH772984 / Otsuka - LARVOL DELTA

Endoplasmic Reticulum Stress Inhibits the Neuronal Differentiation of Human Stem Cells From Apical Papillae by Attenuating the Activity of ERK-IRE1α Axis In Vitro. (PubMed, Int Endod J) - "Severe ER stress inhibits the neuronal differentiation of SCAPs via decreasing ERK1/2 and IRE1α activity, whereas ER stress at an appropriate level is essential for the neuronal differentiation of SCAPs."

Journal • Preclinical • Transplantation • ERN1

ALOXE3 expression predicts poor prognosis and modulates immune infiltration in colon adenocarcinoma. (PubMed, World J Surg Oncol) - "ALOXE3 promotes tumor progression in COAD through activation of the ERK1/2 signaling pathway and exhibits a strong association with the immune cell infiltration of the tumor microenvironment. It may serve as a prognostic biomarker and a potential therapeutic target in COAD. Further studies are warranted to validate its clinical applicability and explore its role in immunotherapeutic approaches."

Biomarker • IO biomarker • Journal • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Solid Tumor • ALOXE3 • LOX

The Piezo1/Extracellular Signal-Regulated Kinase Signal Pathway Regulates Proliferation and Migration of Aortic Vascular Smooth Muscle Cells and Participates in Thoracic Aortic Aneurysm. (PubMed, Heart Lung Circ) - "These data indicate that Piezo1 is significantly activated in aortic VSMCs from patients with TAA, which may be involved in TAA by promoting VSMC proliferation and migration through the ERK signalling pathway. This study provides a new insight into the biological action of the Piezo1/ERK signalling pathway in the pathogenesis of TAA."

Journal • Cardiovascular

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 ERK and PI3K signaling in pancreatic ductal adenocarcinoma (AACR 2025) - "Using SCH772984 (an ERK 1/2 inhibitor) and pictilisib (a class I PI3K inhibitor), we evaluated their combined effects on human PDAC cell lines (MIA PaCa-2 and PANC-1) and a patient-derived xenograft (PDX) cell line. Additionally, preclinical testing in animal models will provide critical insights into the therapeutic potential of this combination. This approach represents a promising avenue for improving PDAC treatment outcomes and addressing unmet needs in this aggressive disease."

Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • KRAS

RRAS and RRAS2 hotspot mutations as novel actionable oncogenic drivers in lung adenocarcinoma (ELCC 2025) - P1 | "Growth of HBEC and Ba/F3 cells expressing RRAS or RRAS2 mutations was sensitive to inhibitors of ERK1/2 (ulixertinib, SCH772984), MEK1/2 (binimetinib), and RAS (RMC-6236). Our findings suggest that patients with RRAS/RRAS2-mutant tumors are likely to derive benefit from RMC-6236 (NCT05379985). Finally, the results are relevant beyond LUAD, as RRAS2 Q72L mutations are also seen in endometrial and ovarian cancers, as well as germ cell tumors."

Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HRAS • KRAS • MAP2K1 • NRAS • RRAS2

P24 Loaded Gelatin-Hydroxyapatite-Tricalcium Phosphate Scaffold Induces Bone Regeneration by Activating the ERK/ELK1/PLA2G3 Pathway. (PubMed, J Biomed Mater Res A) - "For mechanistic investigations, hBMSCs were exposed to both the Gelatin-HA-TCP (P24) scaffold and the ERK inhibitor SCH772984...Therefore, the Gelatin-HA-TCP (P24) scaffold enhances the osteogenic differentiation of hBMSCs and promotes bone regeneration in cranial bone defects by activating the ERK/ELK1/PLA2G3 pathway. It has potential for bone regeneration therapies."

Journal • Fibrosis • Immunology • BMP2 • CD31 • PECAM1 • RUNX2

GPER1/ACACB are potential target genes associated with intracranial aneurysm and vascular endothelial cell senescence. (PubMed, Neurosurg Rev) - "Computational pharmacological screening further identified PD0325901, SCH772984, and selumetinib as potential therapeutic agents targeting both GPER1 and ACACB, offering a dual-pathway therapeutic strategy. The identification of GPER1 and ACACB as potential target genes associated with IA and VECS provides a framework for developing therapies that circumvent hormone dependency, addressing an unmet need in the treatment of IA and age-related vascular pathologies."

Journal • Cardiovascular • Vascular Neurology • ACACB • ER • GPER1

SUCNR1 Deficiency Alleviates Liver Ischemia-Reperfusion Injury by Regulating Kupffer Cell Activation and Polarization Through the ERK/NF-κB Pathway in Mice. (PubMed, Inflammation) - "Sucnr1 deficiency (Sucnr1-/-) and Wild-type mice were treated with or without clodronate before liver IRI modeling, and a co-culture system was established to assess the impact of Sucnr1 deficiency in KCs on hepatocyte viability and apoptosis. The phosphorylation of ERK/NF-κB p65 and M1 polarization in KCs were also inhibited by the SUCNR1 antagonist Compound 4C or ERK inhibitor SCH772984. Together, these findings suggest that SUCNR1 deficiency protects against liver IRI by modulating KC activation and polarization probably through the ERK/NF-κB pathway."

Journal • Preclinical • Cardiovascular • Inflammation • Reperfusion Injury • SUCNR1

Four Novel ROCK1 Inhibitors Suppressing Cytoskeleton and Movement in Breast Cancer Cells. (PubMed, Chem Biodivers) - "We identified four novel ROCK1 inhibitors through virtual screening technology and enzymatic activity assays-bilobetin, SCH 772984, puerarin 6''-O-xyloside, and GSK 650394...Confocal fluorescence imaging revealed that suppression stems primarily from cytoskeletal disruption, thereby impairing migration and invasion, with in vitro inhibition rates of 70-85% and 69-86%, respectively. These findings not only enrich the types of ROCK1 inhibitors, but also provide novel molecular scaffolds for the development of anti-breast cancer drugs."

Journal • Breast Cancer • Oncology • Solid Tumor

Comprehensive Bioinformatics Analysis of Glycosylation-Related Genes and Potential Therapeutic Targets in Colorectal Cancer. (PubMed, Int J Mol Sci) - "Drug sensitivity analysis identified potential therapeutic agents, including Trametinib, SCH772984, and Oxaliplatin, showing differential efficacy between risk groups. These findings enhance our understanding of glycosylation in CRC, identifying it as a critical factor in disease progression and a promising target for future therapeutic strategies."

Biomarker • Journal • Colorectal Cancer • Oncology • Solid Tumor

Targeted Inhibition of NPR3/MAPK Pathway Enhances Dental Pulp Stem Cell Multipotency: Mechanistic Validation Based on Ligustrazine (TMP). (PubMed, Exp Cell Res) - "This study reveals the crucial role of the NPR3/MAPK pathway in regulating DPSCs multipotency and demonstrates that TMP enhances DPSCs functions through targeted inhibition of this pathway, providing new therapeutic strategies and drug targets for dental tissue regeneration."

Journal • NPR3

RRAS and RRAS2 are actionable oncogenic drivers in NSCLC (IASLC-TTLC 2025) - P1 | "Growth of HBEC and Ba/F3 cells expressing RRAS or RRAS2 mutations showed enhanced sensitivity to inhibitors of ERK1/2 (ulixertinib and SCH772984), MEK1/2 (binimetinib), and RAS (RMC-6236). RRASQ87L and RRAS2Q72L are oncogenic in NSCLC and are mutually exclusive with other known lung cancer drivers. Constitutive activation of RRAS and RRAS2 elevated both the MAPK and PI3K-AKT axes and confers susceptibility to targeted inhibition of the MAPK pathway. Notably, the novel pan-RAS inhibitor RMC-6236 diminished RRAS and RRAS2-driven tumor growth in vivo."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HRAS • KRAS • MAP2K1 • NRAS • RRAS2

BRD9 promotes the malignant phenotype of thyroid cancer by activating the MAPK/ERK pathway. (PubMed, Anticancer Drugs) - "After the specific inhibitor of ERK (SCH772984) was applied to thyroid cancer cells (BCPAP cells) overexpressing the BRD9 gene, the results suggested that SCH772984 reverses the high expression of MAPK/ERK pathway-associated protein in BCPAP cells (over-expression BRD9 cells). In conclusion, this study demonstrated that BRD9 was highly expressed in serum and malignant tumor tissues of thyroid cancer patients and further promoted the development of the malignant phenotype of thyroid cancer by activating the MAPK/ERK signaling pathway."

Journal • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • FOS • MYC

Analysis of nitrogen metabolism-related gene expression in hepatocellular carcinoma to establish relevant indicators for prediction of prognosis and guidance of immunotherapy. (PubMed, Comput Methods Biomech Biomed Engin) - "This work created a 12-gene signature based on NM, preliminary investigated immune infiltration in two risk categories, and discovered some possible anti-tumor medications. To sum up, our study findings offer fresh perspectives on the roles played by NM-associated genes in HCC development, prognosis, immunological response, and medication screening."

IO biomarker • Journal • Hepatocellular Cancer • Oncology • Solid Tumor • SPHK1 • YARS1

The prognostic significance and potential mechanism of PFDN4 in hepatocellular carcinoma. (PubMed, Int Immunopharmacol) - "Mechanistically, transcriptome sequencing suggested that PFDN4 modulates HCC cell behavior through the MAPK/ERK signaling pathway, a result confirmed by Western blot and the use of the MAPK/ERK inhibitor SCH772984. Additionally, single-cell RNA sequencing data revealed that PFDN4 is primarily expressed in several immune cell types, including B cells, CD8 + Tex, DC, ILC, mast cells, macrophages, Tprolif, and Treg. In conclusion, our study demonstrates that PFDN4 is upregulated in HCC and drives tumor progression via the MAPK/ERK pathway, highlighting its potential as both a prognostic marker and therapeutic target for HCC."

Journal • Breast Cancer • Colorectal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CD8

Effects of ERK1/2 Inhibitors on the Growth of Acute Leukemia Cells. (PubMed, Anticancer Res) - "ERK1/2 inhibitors may serve as novel molecular-targeted drugs for treating leukemia with NRAS mutations."

Journal • Acute Myelogenous Leukemia • CNS Tumor • Hematological Malignancies • Leukemia • Neuroblastoma • Oncology • Solid Tumor • MYC • NRAS

Ibrutinib Increases Phosphorylation of the Src-Erk1/2 Signaling Pathway in Human Atrial-Specific Cardiomyocytes Derived from Induced Pluripotent Stem Cells (AHA 2024) - "In hiPSC-aCMs, inhibition of CSK by ibrutinib results in increased arrhythmogenic behavior through Erk1/2-dependent phosphorylation. The downstream mechanisms by which this occurs remain unknown and represent novel potential target(s) for AF therapeutics."

Atrial Fibrillation • Cardiovascular • Hematological Malignancies • Oncology • CSK

Colorectal fibroblasts promote malignant phenotype of colorectal cancer cells by activating the ERK signaling pathway (PubMed, Nan Fang Yi Ke Da Xue Xue Bao) - "Colorectal fibroblasts promote malignant phenotype of CRC cells by activating the ERK signaling pathway."

Journal • Colorectal Cancer • Oncology • Solid Tumor • ITGB2

Extracellular Signal-Regulated Kinase Inhibitor SCH772984 Augments the Anti-Cancer Effects of Gemcitabine in Nanoparticle Form in Pancreatic Cancer Models. (PubMed, Int J Mol Cell Med) - "Importantly, GEM did not interfere with the inhibitory effect of SCH772984 on phosphorylated ERK (pERK). Collectively, our studies suggest that combination therapy with GEM and SCH772984 effectively reduced PDAC cell viability and growth, and co-administration of NP encapsulated GEM and SCH772984 in separate NP systems is an effective treatment strategy for PDAC."

Journal • Preclinical • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

RRAS and RRAS2 Mutations Are Oncogenic Drivers in Lung Cancer and are Sensitive to the Pan-RAS Inhibitor RMC-6236 (IASLC-WCLC 2024) - P1 | "ERK1/2 (ulixertinib and SCH772984), MEK1/2 (binimetinib), and PI3K (pictilisib) inhibitors inhibited growth of RRAS Q87L or RRAS2 Q72L cells more potently than cells expressing wildtype proteins. Oncogenic R RAS/RRAS2 mutations were detected in LUAD at a rate similar to some other well-characterized lung cancer drivers, such as HRAS/NRAS hotspot mutations or NRG1 fusions. Our study supports the inclusion of RRAS /RRAS2 into routine molecular diagnostic protocols for precision oncology and clinical development of pan-RAS inhibitors, such as RMC-6236, for patients with these driver mutations in order to fully realize the potential benefit of RAS-targeted therapies."

Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HRAS • KRAS • MAP2K1 • NRAS • NRG1 • RRAS2 • SPRY2

MEK1/2 and ERK1/2 mediated lung endothelial injury and altered hemostasis promote diffuse alveolar hemorrhage in murine lupus. (PubMed, Arthritis Rheumatol) - "Pristane treatment promotes lung endothelial injury and DAH in B6 mice by activating the MEK1/2-ERK1/2 pathway and impairing hemostasis. The hereditary factors determining susceptibility to lung injury and bleeding in pristane-induced lupus are relevant to the pathophysiology of life-threatening DAH in SLE and may help to optimize therapy."

Journal • Preclinical • Hematological Disorders • Immunology • Inflammatory Arthritis • Lupus • Respiratory Diseases • Vasculitis • EGR1 • MAP2K1

Establishment and characterization of six canine hepatocellular carcinoma cell lines. (PubMed, Front Vet Sci) - "Sorafenib showed improved anti-tumor effects when co-treated with SCH772984, an extracellular signal-regulated kinase inhibitor. Our study suggests new therapeutic strategies for canine HCC, and these cell lines are valuable research materials for understanding HCC tumor biology in both humans and dogs."

Journal • Preclinical • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Hepatology • Kidney Cancer • Liver Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • KIT

The Antimicrobial Peptide Tilapia Piscidin 4 Induced the Apoptosis of Bladder Cancer Through ERK/SIRT1/PGC-1α Signaling Pathway. (PubMed, Probiotics Antimicrob Proteins) - "ERK activation, SIRT1/PGC-1α-axis, and TP4-induced apoptosis were all significantly reversed by the ERK inhibitor SCH772984. Finally, the inhibitory effect of TP4 on tumor growth has been confirmed in a zebrafish bladder cancer xenotransplantation model. These findings suggest that TP4 may be a potential agents for human bladder cancer through apoptosis induction, ERK activation, and the promotion of SIRT1-mediated signaling pathways."

IO biomarker • Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Transplantation • BCL2 • CASP3 • CASP9 • PARP1

Protective role of TRPV2 in synaptic plasticity through the ERK1/2-CREB-BDNF pathway in chronic unpredictable mild stress rats. (PubMed, Biochem Biophys Res Commun) - "These findings indicate that TRPV2 activation offers protective effects against depressive-like behaviors and enhances hippocampal synaptic plasticity in CUMS rats via the ERK1/2-CREB-BDNF pathway. TRPV2 emerges as a potential therapeutic target for depression."

Journal • Preclinical • CNS Disorders • Depression • Mood Disorders • Psychiatry • BDNF • TRPV2