SCH772984 / Otsuka - LARVOL DELTA

FGF 13 functions as a regulator of the ERK/aerobic glycolysis axis in the inflammatory state during septic lung injury. (PubMed, Nat Commun) - "In addition, SCH772984 (a selective antagonist of ERK signaling) abolishes the aggravation of inflammation in lungs induced by FGF13 overexpression. Our findings demonstrate that FGF13 promotes inflammatory activation upon septic lung injury through the ERK/aerobic glycolysis axis, thereby accelerating the progression of septic lung injury."

Journal • Infectious Disease • Inflammation • Respiratory Diseases • Septic Shock • FGF • HIF1A

PLA2R1-Mediated ERK-Dependent Ferroptosis: A Key Pathogenic Mechanism in Epileptic Neuronal Injury. (PubMed, Exp Cell Res) - "This study identified the PLA2R1-MEK-ERK-ferroptosis signaling axis, suggesting that PLA2R1 contributes to neuronal ferroptosis through ERK pathway activation in epilepsy. PLA2R1's druggability and ERK inhibitors' clinical safety provide foundation for therapeutic translation."

Journal • CNS Disorders • Epilepsy • ACSL4 • GPX4 • PACERR • PTGS2

GOLGB1 deficiency accelerates intervertebral disc degeneration by activating the MAPK pathway. (PubMed, Sci Rep) - "A MAPK signaling pathway inhibitor (SCH772984) strongly reversed this phenomenon and rescued the degeneration of NP cells. These findings suggest that GOLGB1 may be a potential new target for IDD. GOLGB1 is a protective factor against disc degeneration, and knockdown of GOLGB1 accelerates IDD by activating the MAPK pathway."

Journal

FAM83A promotes the progression of lung squamous cell carcinoma by inducing the epithelial-mesenchymal transition and inhibiting apoptosis via ERK pathway. (PubMed, Lung Cancer) - "FAM83A is crucial in the advancement and spread of LUSC, as it promotes EMT and inhibits apoptosis via the activation of the ERK pathway. These findings highlight its potential as a strategic molecular target for the treatment of LUSC."

IO biomarker • Journal • Non Small Cell Lung Cancer • Oncology • Squamous Cell Carcinoma • BCL2 • CASP3 • CCND1 • CDH1 • CDH2 • FAM83A • VIM

Harnessing Ubiquitin-Proteasome System-Related Genes to Identify Subtypes of Bladder Cancer and Reveal Immune Landscape. (PubMed, Am J Mens Health) - "Somatic mutations demonstrated that the mutation rate of Cluster B was higher than that of Cluster A. In addition, candidate drugs for two clusters of patients were predicted, with Lapatinib, Doramapimod, and SCH772984 may be potential drugs for Cluster A patients. Luminespib, Staurosporine, and Dasatinib may be more suitable for Cluster B patients. The study provides a reference for guiding the clinical treatment of BLCA patients."

IO biomarker • Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • BTLA

Wedelolactone, a Novel TLR2 Agonist, Promotes Neutrophil Differentiation and Ameliorates Neutropenia: A Multi-Omics Approach to Unravel the Mechanism. (PubMed, Adv Sci (Weinh)) - "Similarly, ERK1/2 inhibition by SCH772984 impairs WED-induced neutrophil differentiation and bactericidal activity, decreasing PU.1 and CEBPβ expression without affecting TLR2 levels. These findings position TLR2 as a key therapeutic target for neutropenia, with WED effectively promoting neutrophil differentiation via TLR2 and MEK/ERK pathway activation. This study highlights the therapeutic potential of targeting TLR2 to alleviate neutropenia and underscores the utility of a multi-omics approach in uncovering drug mechanisms."

Journal • Hematological Disorders • Infectious Disease • Neutropenia • Oncology • MAP2K1 • TLR2

Multi-kinase-mediated alterations in Tau phosphorylation, synaptic proteins, and choline metabolism in a human neuronal in vitro model exposed to the elastin-derived hexapeptide VGVAPG. (PubMed, Neuropharmacology) - "Therefore, this study aimed to assess the effects of VGVAPG on Tau phosphorylation, synaptic proteins, choline metabolism, and the involvement of specific kinases in a human neuronal in vitro model, using selective inhibitors (Roscovitine, TDZD-8, SCH772984, SK1). Overall, our findings provide novel insights into the possible contribution of the elastin-derived VGVAPG hexapeptide to the pathogenesis of aging-related neurodegeneration. While our model does not definitively confirm an AD-like phenotype, these results support the need for further investigation in more physiologically relevant systems."

Journal • Preclinical • CNS Disorders • Pain • CDK5 • CIP2A • PTEN

sIL-11 exacerbates cisplatin-induced acute kidney injury by facilitating apoptosis in renal tubular epithelial cells via ERK1/2-Drp1/TFEB-mediated defective autophagy. (PubMed, Cell Signal) - "Mechanistically, IL-11 activated ERK1/2, increased Drp1 phosphorylation and mitochondrial fission, and suppressed TFEB activity to impair lysosomal maturation and autophagic flux; ERK inhibition (SCH772984) and TFEB overexpression rescued TFEB activity, lysosomal markers, and autophagic completion, and reduced apoptosis/senscence. Collectively, these data define an ERK1/2-Drp1/TFEB axis by which IL-11 exacerbates Cis-AKI through mitochondrial dysfunction and autophagic flux disruption, culminating in apoptosis and cellular senescence. Targeting IL-11 or restoring TFEB activity emerges as a mechanism-based strategy to mitigate cisplatin nephrotoxicity."

Journal • Acute Kidney Injury • Metabolic Disorders • Nephrology • Renal Disease • AQP1 • KIM1 • TFEB

The lncRNA MIR4435-2HG Modulates Bladder Cancer Progression and Ferroptosis Through the IQGAP3/Ras/ERK/CREB Pathway. (PubMed, FASEB J) - "The ferroptosis activator RSL3 further attenuated tumor progression in both the knockdown and overexpression models, and combined treatment with the ERK inhibitor SCH772984 synergistically suppressed tumor growth in MIR4435-2HG-overexpressing xenografts. Notably, RSL3 diminished IQGAP3, Ras, ERK, CREB, and GPX4 levels across the experimental conditions. These findings indicate that MIR4435-2HG is a pivotal regulator of bladder cancer progression and ferroptosis via the IQGAP3/Ras/ERK/CREB axis, suggesting that MIR4435-2HG is a potential therapeutic target for intervention."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Sarcoma • Solid Tumor • CKAP4 • GPX4 • MIR4435-2HG

RBMS1-mediates the biogenesis of circNFIB promotes perineural invasion of pancreatic ductal adenocarcinoma via the L1CAM/MAPK pathway. (PubMed, Theranostics) - "The interaction mechanism between circNFIB and IGF2BP3, which enhances L1CAM mRNA stability, was explored using RNA pulldown, mass spectrometry, RNA Immunoprecipitation (RIP), and actinomycin D assays...Finally, we verified circNFIB as a potential therapeutic target that can mitigate the anti-tumor effects of SCH772984 in vivo. RBMS1-mediated circNFIB interacts with IGF2BP3 to stabilize L1CAM mRNA, thereby activating the ERK/MAPK signaling pathway and promoting PNI in PDAC. This study provides a novel perspective on the molecular mechanisms underlying PNI in PDAC and lays the theoretical foundation for circNFIB as a potential therapeutic target for PDAC."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • IGF2BP3 • L1CAM • NFIB

Advances in ERK1/2 inhibition: a medicinal chemistry perspective on structure and regulation. (PubMed, J Enzyme Inhib Med Chem) - "Several molecules-such as SCH772984, SCH900353, ulixertinib (BVD-523), CC-9003, KO-947, AZD0364, norathyriol, and FR180204-are currently in preclinical or clinical trial stages. This review also highlights recent advances in the design and synthesis of ERK inhibitors, emphasising their structural uniqueness and potential to inhibit mutant forms of ERK1/2. Finally, we discuss future directions for the development of ERK1/2 inhibitors as FDA-approved cancer therapeutics."

Journal • Review • Oncology • MAPK1 • MAPK3

α-Glycerol monolaurate promotes tight junction proteins expression through PKC/MAPK/ATF-2 signaling pathway. (PubMed, Front Nutr) - "SCH772984 reduced phosphorylated ATF-2, ZO-1, and OCLN levels (p < 0.05 or p < 0.01), while ATF-2 overexpression rescued this decrease (p < 0.05 or p < 0.01), confirming ATF-2's role in TJ protein upregulation via the MAPK pathway. Our study indicated that α-GML enhanced the expression of TJ proteins through the PKC/MAPK/ATF-2 pathway, thereby enhancing the barrier function of intestinal epithelial cells."

Journal • OCLN • TJP1

Baicalin ameliorates high-fat diet induced MAFLD by inhibiting ERK/PPARγ/CD36 pathway. (PubMed, Phytomedicine) - "This study by using integrates computational prediction demonstrated that PPARγ was the main target of BA, then with multi-level experimental validation, elucidated that BA could ameliorate MAFLD by modulating core ERK/PPARγ/CD36 signaling pathway, highlighting a novel therapeutic target for MAFLD."

Journal • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • CD36 • IL1B • IL6 • PPARG • SCARB1 • TNFA

Human growth hormone-overexpressing adipose-derived stem cells enhance fibroblast activity and accelerate burn wound healing via ERK pathway therapeutic potential of ADSCs in burn wound repair. (PubMed, Regen Ther) - "Western blotting determined ERK activation, and SCH772984 (ERK inhibitor) was used to confirm pathway dependency...Inflammatory cytokines (TNF-α, IL-1β, IL-6) and MDA were lowest, while SOD and CAT were highest in HGH-ADSC-treated wounds (P < 0.05). ADSCs overexpressing HGH promote fibroblast activity, activate ERK signaling, and accelerate burn wound healing, demonstrating strong therapeutic potential."

Journal • Inflammation • Thermal Injury • IL1B • IL6 • TNFA

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