canertinib (CI-1033) / Pfizer - LARVOL DELTA

Baicalin inhibits A549 cells proliferation and EMT through targeting the EGFR pathway. (PubMed, Int Immunopharmacol) - "Baicalin suppresses A549 cell proliferation and EMT via inhibiting the activation of the EGFR signaling pathway."

Journal • Lung Cancer • Oncology • Solid Tumor

Fatty acid metabolism in ischemic stroke: multi-omics biomarker discovery and therapeutic potential of GPR84. (PubMed, BMC Med Genomics) - "This study highlights the role of FAM in IS, identifies VIM, G0S2, and GPR84 as novel diagnostic biomarkers, and positions GPR84 as a therapeutic target, thereby advancing precision diagnosis and treatment."

Biomarker • Journal • Cardiovascular • Ischemic stroke • Oncology • G0S2 • IL17A • TNFA

Effectiveness of step-count monitoring interventions in increasing physical activity among children and adolescents: A systematic review and meta-analysis. (PubMed, Digit Health) - "Step-count monitoring interventions could significantly increase daily steps (MD 1588.83 steps/day; 95% CI 1033.94 to 2143.72; P < 0.01) and tended to significantly reduce SB (MD -3.42 min/day; 95% CI -6.83 to -0.01; P = 0.05)...Moreover, these interventions may serve as an optional approach for increasing MVPA in children. We recommend a "less is more" strategy with regard to step-count monitoring interventions for increasing physical activity in children and adolescents."

Journal • Retrospective data • Review

Metabolic Profiling of Canertinib: A Comprehensive Cross-Species Investigation Using Advanced UPLC-MS/MS and LC-Orbitrap-HRMS Techniques. (PubMed, Biomed Chromatogr) - "This work represents the first cross-species metabolic investigation of canertinib, providing critical insights into interspecies metabolic disparities. The elucidated metabolic framework advances mechanistic understanding of the compound's pharmacological activity and toxicity profiles."

Journal • Hematological Malignancies • Leukemia • Lung Cancer • Metabolic Disorders • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Integrating transcriptomics with disease-gene network and identification of EGFR kinase target: inhibitor discovery through virtual screening of natural compounds for brain cancer therapy. (PubMed, J Biomol Struct Dyn) - "EGFR, a key player in cellular functions and elevated in various cancers, particularly brain cancer, is targeted using small molecule inhibitors like erlotinib and gefitinib...Utilizing molecular docking and dynamic simulation, our study identified five natural compounds-citicoline, silodosin, picroside I, canertinib, and tauroursodeoxycholic acid-as potential EGFR kinase inhibitors...Additionally, it is noteworthy that all the five proposed compounds predicted to penetrate the blood-brain barrier, meeting the essential criteria for reaching brain. We anticipate that this study will provide valuable leads for experimental testing in the laboratory, advancing the prospects of brain cancer management."

Journal • Brain Cancer • Oncology • Solid Tumor • EGFR

SOX9 promotes hepatocyte proliferation via paracrine TGF-a during liver regeneration (APASL 2025) - "Canertinib, an EGFR inhibitor, partially abrogated the enhanced hepatocyte proliferation induced by SOX9. Our findings emphasize that the interplay between SOX9 and HNF4α affects liver regeneration, and unravel the effect of SOX9 promoting hepatocyte proliferation via paracrine TGF-α. Table and Figure:Figure 1."

Hepatology • Liver Failure • SOX9

GFLearn: Generalized Feature Learning for Drug-Target Binding Affinity Prediction. (PubMed, IEEE J Biomed Health Inform) - "Additionally, cross-dataset evaluations and noise perturbation experiments further validated the model's generalizability across different data distributions. Case studies on two drug-target pairs, Canertinib-PIK3C2G and MLN8054-FLT1, provided further evidence of GFLearn's ability to make accurate binding affinity predictions, offering valuable insights for drug screening and repurposing efforts."

Journal • FLT1

Machine Learning-Assisted Drug Repurposing Framework for Discovery of Aurora Kinase B Inhibitors. (PubMed, Pharmaceuticals (Basel)) - " The machine learning models trained for drug repurposing showed satisfying performance and yielded the identification of saredutant, montelukast, and canertinib as potential AurB inhibitors. The candidates demonstrated strong binding energies, key molecular interactions with critical residues (e.g., Phe88, Glu161), and stable MD trajectories, particularly saredutant, a neurokinin-2 (NK2) antagonist. Beyond identifying potential AurB inhibitors, this study highlights an integrated methodology that can be applied to other challenging drug targets."

Journal • Oncology • AURKB

Nutritionally physiological cell culture medium and 3D culture influence breast tumour proteomics and anti-cancer drug effectiveness. (PubMed, Pharmacol Res) - "The number of differentially expressed proteins in the different media was greater in 2D than 3D. We conclude that the risk of qualifying inactive compounds in preclinical assessment may be mitigated using additional models incorporating physiological media and 3-dimensionality."

Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor

Hepatocyte-specific EGFR deletion promotes fibrosis but has no effect on steatosis in fast food diet model of MASLD. (PubMed, Cell Mol Gastroenterol Hepatol) - "Hepatocyte-specific EGFR-KO did not impact steatosis, but enhanced fibrosis in the FFD model of MASLD. Gene-networks associated with lipid metabolism were greatly altered in EGFR-KO, but phenotypic effects might be compensated by alternate signaling-pathways."

Journal • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • EGFR • ERBB3 • FASN • PPARA • PPARG

Human growth factor-mediated signalling through lipid rafts regulates stem cell proliferation, development and survival of Schistosoma mansoni. (PubMed, Open Biol) - "Furthermore, MβCD-mediated lipid raft disruption, and blockade of EGFRs using canertinib, profoundly reduced somule motility and survival, and attenuated stem cell proliferation and somule growth and development particularly to the fast-growing liver stage. These findings provide a novel paradigm for schistosome development and vitality in the host, driven through host-parasite interactions at the tegument, that might be exploitable for developing innovative therapeutic approaches to combat human schistosomiasis."

Journal • Infectious Disease • EGFR • HER-2 • IR

ESCRT-III Component CHMP4C Attenuates Cardiac Hypertrophy by Targeting the Endo-Lysosomal Degradation of EGFR. (PubMed, Hypertension) - "CHMP4C represses cardiac hypertrophy by modulating lysosomal degradation of EGFR and is a potential therapeutic candidate for cardiac hypertrophy."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Targeted Protein Degradation • EGFR

EFFECTS OF HEPATOCYTE-SPECIFIC DELETION OF EGFR IN A DIET-INDUCED NAFLD MOUSE MODEL (AASLD 2023) - "In our previous study, we found that chemical inhibition of EGFR utilizing Canertinib, dramatically reduced hepatocyte steatosis, liver injury, and fibrosis, in a murine fast-food diet (FFD) model, indicating a potential role for EGFR in regulating NAFLD... The hepatocyte-specific deletion of EGFR alters lipid metabolism and fibrosis signaling in a murine FFD model of NAFLD, but is much less effective compared to pharmacological inhibition of EGFR."

Preclinical • Fibrosis • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Oncology • Solid Tumor • EGFR • ERBB3 • FASN • HER-2 • PPARG

Inhibition of ErbB3 and Associated Regulatory Pathways Potently Impairs Malignant Peripheral Nerve Sheath Tumor Proliferation and Survival. (PubMed, Am J Pathol) - "Consistent with this, inhibition of upstream (canertinib, sapitinib, saracatinib, calmodulin) and parallel (AZD1208) signaling pathways involving MAPK and mTOR reduced MPNST proliferation and survival. Src inhibition (saracatinib), like erbB3 knockdown, prevents these phosphorylation events and when combined with trifluoperazine even more effectively reduces proliferation and survival compared to monotherapy. Our findings implicate erbB3, calmodulin, PIM kinases and Src family members as important therapeutic targets in MPNSTs and demonstrate that combinatorial therapies targeting critical MPNST signaling pathways are more effective."

Journal • Brain Cancer • Fibrosis • Genetic Disorders • Neurofibromatosis • Neurofibrosarcoma • Oncology • Sarcoma • Solid Tumor • ERBB3 • NRG1

Determination of Tyrosine Kinase Inhibitors via Capillary Electrophoresis with Tandem Mass Spectrometry and Online Stacking Preconcentration. (PubMed, Pharmaceuticals (Basel)) - "A stacking online preconcentration with a 120 cm-long capillary was used for the determination of bosutinib, dasatinib, canertinib, and erlotinib at physiologically relevant concentrations. The method was validated in terms of linearity, limit of detection, limit of quantification, repeatability of migration times and peak area, and recovery using plasma as a matrix for analytes. The results showed that this method has great promise for use in many analytical tasks, e.g., therapeutic drug monitoring."

Journal

Prognosis and Personalized Treatment Prediction in Different Mutation-Signature Hepatocellular Carcinoma. (PubMed, J Hepatocell Carcinoma) - "Additionally, afatinib and canertinib were recognized which might have potential therapeutic implications in MSC1, and the targets of these drugs presented a higher expression in both gene and protein levels in HCC. Our studies may provide a promising platform for improving prognosis and tailoring therapy in HCC."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Metabolic Disorders • Oncology • Solid Tumor • TMB

Oncogenic fusion of BCAR4 activates EGFR signaling and is sensitive to dual inhibition of EGFR/HER2. (PubMed, Front Mol Biosci) - "Library screening revealed that erlotinib, canertinib, and lapatinib demonstrated inhibitory effects on cell migration. In addition, canertinib treatment restored E-cadherin expression and reduced the expression of epithelial-mesenchymal transition regulatory factors such as Slug and Snail. Taken together, these results suggest that EGFR/HER2 inhibitors are potential therapeutic options for BCAR4 fusion-harboring lung cancer patients, even in the absence of EGFR mutations."

Journal • Lung Cancer • Oncology • Solid Tumor • BCAR4 • CD63 • CDH1 • SNAI2

Identifying Drug Candidates for Pancreatic Neuroendocrine Tumors Based on Differently Expressed Genes (IHPBA 2022) - "Drug candidates targeted against pNET were identified based on differentially expressed genes. Available genetic atlas data may help identify agents with therapeutic efficacy to treat pNET patients using a more targeted approach."

Endocrine Cancer • Graft versus Host Disease • Immunology • Infectious Disease • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Pertussis • Respiratory Diseases • Solid Tumor • CCL20 • CXCL8 • GNG4 • LEP • LEPR

Predicting Novel Drug Candidates for Pancreatic Neuroendocrine Tumors via Gene Signature Comparison and Connectivity Mapping. (PubMed, J Gastrointest Surg) - "Using available genetic atlas data, potential drug candidates for treatment of pNETs were identified based on differentially expressed genes. These results may help focus efforts on identifying targeted agents with therapeutic efficacy to treat patients with pNETs."

Journal • Endocrine Cancer • Graft versus Host Disease • Immunology • Infectious Disease • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Pertussis • Respiratory Diseases • Solid Tumor • CCL20 • CXCL8 • GNG4 • LEP • LEPR

M1 Macrophages Enhance Survival and Invasion of Oral Squamous Cell Carcinoma by Inducing GDF15-Mediated ErbB2 Phosphorylation. (PubMed, ACS Omega) - "The ErbB2 phosphorylation inhibitor (CI-1033) and GDF15 knockout cell lines were used to appraise the role of ErbB2 and GDF15 in mediating the effects of M1-CM...Our results demonstrate that M1 macrophages induce the proliferation, migration, invasion, and xenograft development of OSCC cells. Mechanistically, this protumor effect of M1 macrophages is partly associated with inducing GDF15-mediated ErbB2 phosphorylation."

Journal • Oncology • Oral Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • GDF15 • HER-2

Potential applications of clickable probes in EGFR activity visualization and prediction of EGFR-TKI therapy response for NSCLC patients. (PubMed, Eur J Med Chem) - "These clickable probes are versatile chemical tools based on the key pharmacophore (4-anilinoquinazoline) of EGFR-TKIs (e.g., canertinib, dacomitinib and afatinib) and are able to irreversibly target the kinase domain of EGFR. Moreover, 13 was applied to visualize EGFR mutant activity in tumour tissues from non-small-cell lung cancer (NSCLC) xenograft mouse models, and patients with NSCLC for the prediction of EGFR-TKI sensitivity. These results demonstrate that strategically designed EGFR-TKI-based probes allow discriminating EGFR mutations in human tissues and hold promise as useful diagnostic tools in predicting EGFR-TKI therapy response."

Clinical • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Mechanism of sensitivity to TPF chemoagents and its potential alternative of erbB2 in oral cancer with GDF15 overexpression. (PubMed, Cancer Sci) - "The aim of this study was to: 1) explore the potential mechanism of cancer cell sensitivity to cisplatin, docetaxel, and 5-fluorouracil (TPF) in oral squamous cell carcinoma (OSCC) patients overexpressing growth differentiation factor 15 (GDF15); and 2) identify potential alternative agents for patients who might not benefit from inductive TPF chemotherapy...When OSCC cells with GDF15 overexpression were treated with the erbB2 phosphorylation inhibitor, CI-1033, cell proliferation, and xenograft growth colony formation was significantly blocked (P<0.05)...GDF15 overexpression promotes OSCC proliferation via erbB2 phosphorylation. Thus, ErbB2 inhibitors may represent potential targeted drugs or an alternative therapy for OSCC patients with GDF15 overexpression."

Journal • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CASP9 • GDF15 • HER-2

New C2- and N3-Modified Thieno[2,3-d]Pyrimidine Conjugates with Cytotoxicity in the Nanomolar Range. (PubMed, Anticancer Agents Med Chem) - "The thienopyrimidines tested in vitro towards human cancer HT-29, MDA-MB-231, HeLa, HepG2 and normal human Lep3 cell lines demonstrated cytotoxicity in nanomolar range. It was established that compounds 9, 10 and 21 showed many times lower toxicity against normal Lep3 cells that can provide a high selectivity towards all four cancer cell lines at small concentrations. Based on the analysis of the structure-activity relationship, the observed trends in the cytotoxicity could be related to the lipophilicity and the topological polar surface area of the tested compounds. The docking study on the potential of the new thieno[2,3-d]pyrimidine-4-ones to interact with mutant VB-Raf showed that the compounds might be able to stabilize the enzyme in its inactive form."

Journal • Oncology

Effective degradation of EGFR mutant proteins by CRBN-based PROTACs through both proteosome and autophagy/lysosome degradation systems. (PubMed, Eur J Med Chem) - "Pre-incubation with canertinib, pomalidomide or ubiquitination inhibitor MLN4924 totally blocked EGFR degradation by PROTACs. Elevating autophagy activities enhanced EGFR degradation and cell apoptosis induced by PROTACs. Our research not only offered a novel PROTAC tool to target EGFR TKI drug resistance in lung cancer, but also firstly demonstrated that the involvement of autophagy/lysosome system in PROTAC- mediated target protein degradation."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • BRCA1 • CRBN • EGFR

Reconstruction of BRAFV600E driven colorectal carcinogenesis and identification of novel drug combinations involving BRAF and RTK inhibitors (AACR 2018) - "...These trials often involve the combination of BRAF inhibitors (BRAFi) and/or MEK inhibitors with anti-EGFR antibodies such as cetuximab or panitumumab...Importantly, combination of BRAFi (vemurafenib, dabrafenib or encorafenib) with inhibitors dually targeting the EGFR and HER2 (lapatinib, canertinib or afatinib) significantly reduced the metabolic activity and proliferation of CRC cells...Using a Vil-CreERT2 transgene, we were able to induce expression of oncogenic BRAF and dominant-negative p53R172H in organoids by 4-hydroxy-tamoxifen mediated Cre activation. We demonstrate that the sudden expression of BRAFV600E and TP53R172H induce marked morphological and molecular changes in small and large intestinal crypts. This organoid model system represents an excellent tool to better understand key characteristics of BRAF mutant CRC such as intrinsic aggressiveness, poor differentiation and resistance to BRAFi."

Colorectal Cancer