AG-1296 / Friedrich-Schiller University of Jena, Wuhan University, Zhejiang University - LARVOL DELTA

Echinococcus multilocularis infection induces pathological angiogenesis in mouse liver via PDGFR/PI3K/AKT/FAK signaling pathway (EASL 2025) - "Our findings provide new perspectives on how E. multilocularis infection triggers pathological angiogenesis in the host liver, and may provide a novel anti-angiogenic therapeutic strategy against E. multilocularis infection."

Preclinical • Infectious Disease • Oncology • PDGFRB

Role and Mechanism of Lamellar Derived Growth Factor /AKT Pathway in Ventricular Remodeling Induced by Pressure Overload. (PubMed, Cell Biochem Biophys) - "E group mice were treated with the PDGF receptor inhibitor AG1296 and PBS solution after AC surgery...Inhibition of the PDGF/AKT signaling pathway effectively mitigates myocardial cell hypertrophy and ventricular remodeling. These findings offer novel potential targets and therapeutic strategies for the treatment of pressure overload-related heart failure."

Journal • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology

Curative effects and mechanisms of AG1296 and LY294002 co-therapy in Angiostrongylus cantonensis-induced neurovascular unit dysfunction and eosinophilic meningoencephalitis. (PubMed, J Microbiol Immunol Infect) - "These findings demonstrate the potential of PDGFR-β inhibitor AG and PI3K inhibitor LY co-therapy as anti-A. cantonensis drug candidates through improved neurovascular unit dysfunction and reduced inflammatory response."

Journal • CNS Disorders • Infectious Disease • Inflammation • Targeted Protein Degradation • IL6 • MMP9 • PDGFRB • S100B

Lysyl Oxidase Promotes the Formation of Vasculogenic Mimicry in Gastric Cancer through PDGF-PDGFR Pathway. (PubMed, J Cancer) - "With inhibition of PDGFRα and PDGFRβ using AG1295 or AG1296, VM formation in gastric cancer cells decreased (P <0.05), but the number of VM structures increased while LOX was added (P < 0.05). LOX partially promotes the formation of VM in gastric cancer through the PDGF-PDGFR signaling pathway."

Journal • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD34 • LOX • PDGFRA • PDGFRB

PDGF-AA guides cell crosstalk between human dental pulp stem cells in vitro via the PDGFR-α/PI3K/Akt axis. (PubMed, Int Endod J) - "This research demonstrated that PDGF-AA can enhance Cx43-mediated GJIC in DPSCs via the PDGFR-α/PI3K/Akt axis, which provides new cues for dental pulp regeneration from the perspective of intercellular communication."

Journal • Preclinical • PDGFRA

The number of primitive endoderm cells in the inner cell mass is regulated by platelet-derived growth factor signaling in porcine preimplantation embryos. (PubMed, Anim Biosci) - "The PDGF receptor inhibitor AG1296 (5 μM) suppressed SOX17-positive cells without reducing SOX2-positive cells in both parthenogenetic activated and in vitro fertilized embryos...The PDGF receptor might control the number of PrE cells by repressing the proapoptotic gene Txnip. Our results can help to isolate Epi-specific cell lines from blastocysts."

Journal • Preclinical • PDGFRA • SOX17 • SOX2 • TXNIP

The pdgfra-regulating lncrna linc02283 is amplified in high-grade glioma and facilitates gliomagenesis (SNO 2022) - "Inhibition of PDGFRA signaling using AG1296, represses the high endogenous LINC02283 levels in PDGFRA-mutant GSCs, reduces LINC02283 induced signaling in PDGFRA-wt GSCs, and suppresses cell proliferation in both the cellular models of HGG...Thus, blocking the LINC02283-PDGFRA interaction could be a plausible therapeutic strategy in HGG. Altogether, our results provide strong evidence of lncRNAs as drivers of PDGF Receptor A activity and HGG progression and support the potential of lncRNAs as possible therapeutic targets."

Brain Cancer • Glioma • Oncology • Solid Tumor • PDGFRA

Small-molecule inhibitor - tyrphostin AG1296 regulates proliferation, survival and migration of rhabdomyosarcoma cells. (PubMed, J Physiol Pharmacol) - "To conclude, tyrphostin AG1296 is a promising compound in the treatment of alveolar RMS. Undoubtedly, a better knowledge of receptor pathomechanism of tyrosine kinases may contribute to developing new, more effective ways of RMS treatment."

Journal • Oncology • Rhabdomyosarcoma • Sarcoma • Solid Tumor • AKT1

[VIRTUAL] Role of pericytes in experimental pneumococcal meningitis: investigations in a zebrafish model (ECCMID 2021) - "Methods To study whether PM is associated with changes in the brain pericyte population, we assessed pericyte coverage of brain vessels during the course of the disease, using the transgenic zebrafish line TgBAC(pdgfrb:EGFP)/Tg(fli1a:Myr-mCherry) and performing confocal microscopy imaging.Subquently, we evaluated the impact of pericyte depletion on the disease course by reducing brain pericyte populations of zebrafish embryos by treatment with the PDGFRß inhibitor AG1296... Our study shows that pericytes play a key role in the pathogenesis of PM, and appear to have a protective effect on the brain . Further experimental studies should determine the exact function of pericytes during PM."

CNS Disorders • Infectious Disease • Inflammation • Pneumococcal Infections • Pneumonia • Vascular Neurology • FLI1 • PDGFRB

iPSC-endothelial cell phenotypic drug screening and in silico analyses identify tyrphostin-AG1296 for pulmonary arterial hypertension. (PubMed, Sci Transl Med) - "Specifically, AG1296 up-regulated small mothers against decapentaplegic (SMAD) 1/5 coactivators, cAMP response element-binding protein 3 (CREB3), and CREB5: CREB3 induced inhibitor of DNA binding 1 and downstream genes that improved vascular function. Thus, drug discovery for PAH can be accelerated by combining phenotypic screening with in silico analyses of publicly available datasets."

Journal • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • CREB5 • SMAD4

PDGF-PDGFR network differentially regulates, myogenic cell fate, migration, proliferation, and cell cycle progression. (PubMed, Cell Signal) - "PDGFRs inhibitor AG1296 inhibited ERK1/2 and AKT activation, myoblast migration, proliferation, and cell cycle progression induced by PDGF-AB and PDGF-BB...Also, myogenic differentiation reduced the expression of both PDGFRα and PDGFRβ, whereas forced PDGFRα expression impaired myogenesis. Thus, our data highlight PDGF signaling pathway to stimulate satellite cell proliferation aiming to enhance skeletal muscle regeneration and provide a deeper understanding of the role of PDGF signaling in non-fibroblastic cells."

Journal • PDGFRA • PDGFRB

The cross-talk between TGF-β and PDGFRα signaling pathways regulates stromal fibro/adipogenic progenitors' fate. (PubMed, J Cell Sci) - "Finally, pharmacological inhibition of PDGFRα activity with AG1296 impaired TGF-β-induced extracellular matrix remodeling, Smad2 signaling, myofibroblast differentiation, and migration of MSCs. Thus, our work establishes a functional cross-talk between TGF-β and PDGFRα signaling pathways that is involved in regulating the biology of FAPs/MSCs."

Journal • Fibrosis • Immunology