AG1478 / IDT Australia - LARVOL DELTA

Cell-cell communication shapes the impact of obesity-associated stressors on human vascular cells. (ESPE-ESE 2025) - "Incubation of cells with either or both stimuli in the presence of AG1478/EGF revealed that MS-induced cell proliferation, dglucose, dlactate and ATP production seems to be EGFR dependent... This study indicates that the transcriptome and functional profile of cells are profoundly influenced by the cell culture type, underscoring the critical role of cell interactions in cellular behavior. The effects of MS in different vascular cells are, at least partially, mediated by EGFR. In few cases, these effects are further altered by HS."

Cardiovascular • Genetic Disorders • Inflammation • Obesity • EGFR

Activation of GPER1 alleviates white matter injury by promoting microglia M2 polarization through EGFR/Stat3 pathway in intracerebral hemorrhage mice. (PubMed, J Stroke Cerebrovasc Dis) - "Collectively, our findings demonstrated activation of GPER1 alleviated WMI via modulating microglia M2 polarization after ICH through EGFR/Stat3 signaling pathway."

Journal • Preclinical • Cerebral Hemorrhage • Hematological Disorders • Inflammation • Solid Tumor • GPER1 • IL10 • IL1B • IL4 • TNFA

Assessing the impact of CD73 inhibition on overcoming anti-EGFR resistance in glioma cells. (PubMed, Oncol Res) - "The U251 GB cell line was treated with AG1478, an EGFR inhibitor, and the resistance markers MRP-1, PD-L1, and CD73 were evaluated using flow cytometry...In summary, our findings indicate that CD73 inhibition has a modest effect in overcoming resistance to EGFR monotherapy in vitro. Thus, further in vivo studies are needed, as the inhibition of both EGFR and CD73 affects cells in the tumor microenvironment and could potentially enhance anti-tumor immunity."

IO biomarker • Journal • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • CD73 • CTLA4 • NT5E • PD-L1

A Macrophage-smooth Muscle Cell Axis Influences Vascular Remodeling Through Activation of the EGFR Pathway in Giant Cell Arteritis (ACR Convergence 2024) - P=N/A | "Conversely, AG1478, an EGFR inhibitor, completely inhibited both VSMC migration and proliferation, suggesting a key role for the EGFR pathway in VSMC proliferation and migration. Our study shows that both AREG and HBEGF may play a role in the pathophysiology of GCA, especially in the remodeling phase of the disease. Further studies are needed to explore other EGFR ligands and to decipher the pathophysiological mechanisms between macrophages, VSMC and fibroblasts in GCA."

Giant Cell Arteritis • Immunology • Inflammation • Vasculitis • AREG • GLI2 • HBEGF

Transactivation of the EGF receptor as a novel desensitization mechanism for G protein-coupled receptors, illustrated by dopamine D2-like and β2 adrenergic receptors. (PubMed, Cell Mol Biol Lett) - "The EGFR inhibitor AG1478 prevented both desensitization and the associated cellular events...These findings suggest that EGFR transactivation diversifies pathways involved in ERK activation through the EGFR signaling system and also mediates GPCR desensitization. Alongside the widely accepted steric hindrance model, these findings offer new insights into understanding the mechanisms of GPCR desensitization, which occurs through complex cellular processes."

Journal • Targeted Protein Degradation

The influence of the NRG1/ERBB4 signaling pathway on pulmonary artery endothelial cells. (PubMed, Pulm Circ) - "NRG1 inhibition in HPAECs apoptosis can be partially reversed by inhibiting ERBB4 expression with AG1478. ERBB4 has the potential to be a novel biological marker of PE."

Journal • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Pulmonary Embolism • Respiratory Diseases • NRG1 • PI3K

Silencing Nrf2 in cisplatin resistant non-small cell lung cancer cells augments sensitivity towards EGFR inhibitor. (PubMed, Toxicol In Vitro) - "Recently, non-small cell lung cancer (NSCLC) has been the prime concern of cancer clinicians due to its high mortality rate worldwide. Moreover, genetic inhibition of Nrf2 with siRNA in CisR cells showed increased sensitivity towards the EGFR tyrosine kinase inhibitor (TKIs), AG1478. Our study, therefore suggests the use of Nrf2 inhibitors in combinatorial therapy with EGFR TKIs for the treatment of resistant NSCLC."

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

Recombinant tissue plasminogen activator protects neurons after intracerebral hemorrhage through activating the PI3K/AKT/mTOR pathway. (PubMed, Neural Regen Res) - "Moreover, the phosphoinositide 3-kinase inhibitor LY294002 abrogated the neuroprotective effects of recombinant tissue plasminogen activator in inhibiting excessive apoptosis, autophagy, and endoplasmic reticulum stress. It has been revealed that the epidermal growth factor receptor inhibitor AG-1478 reversed the effect of recombinant tissue plasminogen activator on the phosphoinositide 3-kinase/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin pathway. These findings suggest that recombinant tissue plasminogen activator exerts a direct neuroprotective effect on neurons following intracerebral hemorrhage, possibly through activation of the phosphoinositide 3-kinase/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin pathway."

Journal • Cerebral Hemorrhage • Hematological Disorders • EGFR

Lacticaseibacillus rhamnosus GG alleviates sleep deprivation-induced intestinal barrier dysfunction and neuroinflammation in mice. (PubMed, Food Funct) - "In terms of mechanism, it was found that AG1478, an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, could diminish the protective effects of LGG. In conclusion, LGG demonstrated the ability to alleviate SD-induced intestinal barrier dysfunction through EGFR activation and alleviate neuroinflammation."

Journal • Preclinical • CNS Disorders • Inflammation • Mental Retardation • Psychiatry • EGFR

PAR2 activation on human tubular epithelial cells engages converging signaling pathways to induce an inflammatory and fibrotic milieu. (PubMed, Front Pharmacol) - "A TGF-β receptor-1 (TGF-βRI) kinase inhibitor, SB431542, and an EGFR kinase inhibitor, AG1478, ameliorated 2F induced secretion of TNF, CSF2, MMP-9, and PAI-1. Whilst an EGFR blocking antibody, cetuximab, blocked PAR2 induced EGFR and ERK phosphorylation, a TGF-βRII blocking antibody failed to influence PAR2 induced secretion of PAI-1...In summary PAR2 activates critical inflammatory and fibrotic signalling pathways in human kidney tubular epithelial cells. Biased antagonists of PAR2 should be explored as a potential therapy for CKD."

Journal • Chronic Kidney Disease • Fibrosis • Immunology • Inflammation • Nephrology • Renal Disease • CSF2 • CTGF • GPRC6A • MMP9 • SMAD2 • TGFB1

Insights into Halogen-Induced Changes in 4-Anilinoquinazoline EGFR Inhibitors: A Computational Spectroscopic Study. (PubMed, Molecules) - "EGFR inhibitors like AG-1478 and PD153035, featuring a 4-anilinoquinazoline moiety, have garnered global attention for their potent therapeutic activities...Additionally, optical spectral shifts correlate with potency, as TKI-Cl and TKI-Br exhibit blue shifts from their global minimum structures, in contrast to other TKI-X. This suggests that optical reporting can effectively probe drug potency and conformation changes."

Journal • Oncology

The roles of tight junction protein cingulin in human endometrioid endometrial cancer. (PubMed, Tissue Barriers) - "In 2D and 2.5D cultures, treatment with β-estradiol with or without EGF or TGF-β decreased CGN expression and the epithelial permeability barrier and enhanced cell migration, and pretreatment with EW7197+AG1478, U0126 or an anti-IL-6 antibody prevented this. In conclusion, CGN, with tTJ proteins might suppress the malignancy of human EEC and its complex proteins are sensitive to estrogen and growth factors derived from stromal cells."

Journal • Endometrial Cancer • Oncology • Solid Tumor • CGN • EGF • LSR • TGFB1

EGFR/TKIs induce excessive apoptosis of bladder carcinoma cells by arresting cell cycle and promoting mitochondrial peroxidation damage. (PubMed, Cell Mol Biol (Noisy-le-grand)) - "Besides, the research team further observed that AG1478 also promoted pyroptosis in T24 cells, and its mechanism is related to the induction of mitochondrial oxidative stress damage. The findings lay a more reliable foundation for the future application of EGFR-TKIs in BC."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Effects of PM2.5 on mucus hypersecretion in airway through miR-133b-5p/EGFR/Claudin1/MUC5AC axis. (PubMed, Aging (Albany NY)) - "PM2.5 inhibited the expression of miR-133b-5p to activate the EGFR/MAPK signal pathway, induce the hypersecretion of MUC5AC, thus aggravating PM2.5-related airway inflammation in rats."

Journal • Inflammation • Respiratory Diseases • CLDN1 • EGFR • MIR133B • MUC5AC • TNFA

17-β-estradiol and phytoestrogens elicit NO production and vasodilatation through PI3K, PKA and EGF receptors pathways, evidencing functional selectivity. (PubMed, Eur J Pharmacol) - "Multiple estrogen receptor activity was inferred based on the reduction of DAF-NO signals; G-36 (GPER antagonist) reduced 75 % of all estrogen responses, while fulvestrant (selective nuclear receptor antagonist) reduced significantly more the phytoestrogens responses than E2...Wortmannin or LY-294002 (PI3K inhibitors), reduced by 90% the E2-evoked signal while altering significantly less the DAI-induced response...Epidermal growth factor (EGF) induced NO production, cell treatment with AG-1478, an EGF receptor kinase inhibitor reduced 90% DAI-induced response while only 53% the E2-induced signals; highlighting GPER induced EGF receptor trans-modulation. Receptor functional selectivity may explain distinct signalling pathways mediated by E2 and phytoestrogens."

Journal

EGF-like growth factors upregulate pentraxin 3 expression in human granulosa-lutein cells. (PubMed, J Ovarian Res) - "In addition, we found that the upregulation of PTX3 expression triggered by the EGF-like factors was completely reversed by either pretreatment with the epidermal growth factor receptor (EGFR) inhibitor, AG1478, or knockdown of EGFR, suggesting that EGFR is crucial for activating the ERK1/2 signaling pathway in hGL cells. Overall, our findings indicate that AREG, BTC, and EREG may modulate human cumulus expansion during the periovulatory stage through the upregulation of PTX3."

Journal • BTC • EGF • EREG • PTX3

ERBB1 alleviates secondary brain injury induced by experimental intracerebral hemorrhage in rats by modulating neuronal death via PLC-γ/PKC pathway. (PubMed, CNS Neurosci Ther) - "ERBB1 can improve SBI and has a neuroprotective effect in experimental ICH rats via PLC-γ/PKC pathway."

Journal • Preclinical • Alzheimer's Disease • Cerebral Hemorrhage • CNS Disorders • Cognitive Disorders • Hematological Disorders • Vascular Neurology • EGFR

Neuropathological stage-dependent proteome mapping of the olfactory tract in Alzheimer's disease: From early olfactory-related omics signatures to computational repurposing of drug candidates. (PubMed, Brain Pathol) - "These validation experiments revealed that pretreatment of human neuron-like SH-SY5Y cells with the EGFR inhibitor AG-1478 showed a neuroprotective effect against hydrogen peroxide-induced damage while the pretreatment with the Aurora kinase inhibitor Reversine reduced amyloid-beta (Aβ)-induced neurotoxicity. Taken together, our data pointed out that OMSs may be useful as substrates for drug repurposing to propose novel neuroprotective treatments against AD."

Journal • Alzheimer's Disease • CNS Disorders • Dementia • APP • IGF1

Transforming Growth Factor α Evokes Aromatase Expression in Gastric Parietal Cells during Rat Postnatal Development. (PubMed, Int J Mol Sci) - "By contrast, administration of AG1478 (5 mg/kg BW), a protein tyrosine kinase inhibitor with high selectivity for the epidermal growth factor receptor and acting as an antagonist of TGFα, led to the suppression of aromatase expression. In fact, TGFα expression in the gastric fundic gland isthmus began around 20 days after birth in normal rats as did that of aromatase, which indicates that TGFα might induce the expression of aromatase in the parietal cells concomitantly."

Journal • Preclinical • CYP19A1 • EGFR • TGFA

Epidermal growth factor receptor phosphorylation contributes to levobupivacaine-induced contraction in isolated rat aorta. (PubMed, Eur J Pharmacol) - "The EGFR tyrosine kinase inhibitor AG1478, matrix metalloproteinase (MMP) inhibitor GM6001, Src kinase inhibitors PP1 and PP2, and JNK inhibitor SP600125 attenuated levobupivacaine-induced contractions. Furthermore, AG1478 inhibited levobupivacaine-induced calcium increases in VSMCs. Collectively, these findings suggest that levobupivacaine-induced EGFR phosphorylation, which may occur via the Src kinase-MMP pathway, contributes to vasoconstriction via JNK phosphorylation and increased calcium levels."

Journal • Preclinical • Anesthesia • EGFR

The interplay between the epithelial permeability barrier, cell migration and mitochondrial metabolism of growth factors and their inhibitors in a human endometrial carcinoma cell line. (PubMed, Tissue Barriers) - "EW-7197 (a TGF-β receptor inhibitor), AG1478 (an EGFR inhibitor) and SP600125 (a JNK inhibitor) affected the epithelial permeability barrier, cell migration and mitochondrial metabolism and prevented the changes induced by TGF-β and EGF in 2D and 2.5D cultures. In conclusion, TGF-β and EGF promoted the malignancy of endometrial cancer via interplay among the epithelial permeability barrier, cell migration and mitochondrial metabolism. EW-7197 and AG1478 may be useful as novel therapeutic treatments options for endometrial cancer."

Journal • Preclinical • Endometrial Cancer • Endometriosis • Gynecology • Oncology • Solid Tumor • Women's Health • TGFB1

Treadmill Running Regulates Adult Neurogenesis, Spatial and Non-spatial Learning, Parvalbumin Neuron Activity by ErbB4 Signaling. (PubMed, Cell Mol Neurobiol) - "Here, we first conducted a four-week study on the effects of AG1478, an ErbB4 inhibitor, on memory and neurogenesis...These results suggest exercise may regulate adult neurogenesis and PV neuron activity through ErbB4 signaling. Overall, these findings provide further evidence of the importance of exercise for neurogenesis and suggest that targeting ErbB4 may be a promising strategy for improving memory and other cognitive functions in individuals with mental disorders."

Journal • CNS Disorders • Mental Retardation • Psychiatry • Schizophrenia • NRG1

The Notch1/Hes1 pathway regulates Neuregulin 1/ErbB4 and participates in microglial activation in rats with VPA-induced autism. (PubMed, Prog Neuropsychopharmacol Biol Psychiatry) - "The present study showed that AG1478, which is an ErbB4 inhibitor, ameliorated the autism-like behaviors in a VPA-induced autism rat model, reduced abnormal microglial activation, and decreased NRG1 and Iba-1 colocalization; however, AG1478 did not alter Notch1/Hes1 activity. These results demonstrated that Notch1/Hes1 may participate in the microglial activation in autism by regulating NRG1/ErbB4, revealing a new mechanism underlying the pathogenesis of autism."

Journal • Preclinical • Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Genetic Disorders • Psychiatry • ERBB4 • HES1 • NOTCH1 • NRG1

Mesenchymal Stem Cells Combined With Electroacupuncture Treatment Regulate the Subpopulation of Macrophages and Astrocytes to Facilitate Axonal Regeneration in Transected Spinal Cord. (PubMed, Neurospine) - "These findings showed that MSCs+EA treatment synergistically regulated the microglia/macrophage subpopulation to reduce inflammation, the formation of neurotoxic A1 astrocytes, and glial scars. This was achieved by downregulating the ErbB1-STAT3 signal pathway, thereby providing a favorable microenvironment conducive to axonal regeneration after SCI."

Journal • CNS Disorders • Oncology • Orthopedics • Transplantation • EGFR • GFAP • IL10 • IL1B • TNFA

G protein‑mediated EGFR transactivation is a common mechanism through which the CXCL12 receptors, CXCR4 and CXCR7, control human cancer cell migration. (PubMed, Oncol Rep) - "Furthermore, chemotactic responses to CXCL12 were additionally prevented by inhibiting EGFR activity via AG1478 and Src kinase activity via Src inhibitor‑1. In conclusion, the results of the present study suggest that G protein‑ and Src‑dependent transactivation of EGFR is a common mechanism through which CXCL12‑bound CXCR4 and/or CXCR7 control cancer cell migration and metastasis. These findings highlight EGFR as a potential therapeutic target that interferes with CXCL12‑induced cancer expansion."

Journal • Infectious Disease • Oncology • Respiratory Diseases • ACKR3 • CXCL12 • CXCR4 • EGFR