LY294002 / Eli Lilly - LARVOL DELTA

Signaling pathway underlying autocrine activation of ecdysteroidogenesis in prothoracic glands of Bombyx mori. (PubMed, Insect Biochem Mol Biol) - "Treatment with LY294002 and rapamycin reduced 4E-BP phosphorylation, indicating the involvement of the PI3K/TOR pathway...Treatment with either validamycin A or the glycolysis inhibitor 2-deoxy-D-glucose (2-DG) suppressed autocrine activation of ecdysteroidogenesis, clearly indicating that both Treh activity and glycolysis are involved...Using a specifically generated anti-bombyxin-Z1 antibody, the presence of bombyxin-Z1 protein was confirmed. To my knowledge, this is the first study to elucidate the signaling cascade involved in autocrine activation of ecdysteroidogenesis in an insect system."

Journal • EGF

4-Phenylbutyrate Induces Functional Elongation of the Microglial Process Through Activation of Akt. (PubMed, Neurochem Res) - "Moreover, 4-PBA did not prevent LPS-induced inflammatory responses in cultured microglia and prefrontal cortex or LPS-induced sickness behaviors when cultured microglia or mice were treated with LY294002. Altogether, these results indicate that 4-PBA induces microglial process elongation in an Akt-dependent manner, which may underlie the anti-neuroinflammatory properties of 4-PBA."

Journal • Inflammation

Quercetin reduces expression of ATP‑binding cassette transporters by regulating the PTEN/PI3K/AKT signaling pathway in breast cancer cells. (PubMed, Oncol Rep) - "The present study investigated the mechanism by which Que regulates ATP‑binding cassette (ABC) transporter expression in MCF‑7 cells using a PTEN overexpression plasmid and the PI3K inhibitor LY294002...The results of the present study demonstrated that Que suppresses cell viability and induces apoptosis in MCF‑7 cells. Moreover, it enhances intracellular drug accumulation and downregulates ABC transporter expression by modulating the PTEN/PI3K/AKT signaling pathway."

Journal • Breast Cancer • Oncology • Solid Tumor • ABCG2 • PTEN

Extracorporeal cardiac shock wave stimulation enhances the therapeutic efficacy of intravenously delivered endothelial colony-forming cells via PI3K/AKT signaling in a rat myocardial infarction model. (PubMed, Stem Cell Res Ther) - "In conclusion, this study demonstrates that preconditioning ECFCs with ECSW significantly enhances their therapeutic efficacy for myocardial infarction, improving both cardiac function and structural repair. These benefits are mediated primarily through activation of the PI3K/AKT signaling pathway, which augments cell homing, paracrine activity, and survival, thereby providing a novel and promising strategy for cardiac regeneration."

IO biomarker • Journal • Preclinical • Cardiovascular • Fibrosis • Immunology • Myocardial Infarction • Transplantation • APOE • BCL2 • CASP3 • CD31 • NOS3 • PECAM1

Asperosaponin VI enhances stress resilience by activating hippocampal neural stem cells. (PubMed, Phytomedicine) - "Our findings identify ASA-VI as a novel agent that enhances stress resilience and prevents depression by activating the PI3K/Akt pathway in NSC."

Journal • CNS Disorders • Depression • Psychiatry • GFAP

BRG1 orchestrates diabetic corneal neuropathy via PI3K/AKT-mediated glycolytic reprogramming. (PubMed, Eye Vis (Lond)) - "Glycolytic reprogramming is a critical driver of DCN progression. BRG1 activates PI3K/AKT signaling to enhance glycolytic flux, thereby regulating DCN pathogenesis. Targeting this axis may offer novel therapeutic strategies."

Journal • CNS Disorders • Diabetes • Diabetic Neuropathy • Metabolic Disorders • Pain • Type 1 Diabetes Mellitus • AKT1 • SMARCA4

MICALL2 promotes angiogenesis of colorectal cancer by regulating the EGFR/PI3K/AKT/KLF5/VEGFA axis. (PubMed, Biochem Pharmacol) - "Pharmacological inhibition of PI3K via LY294002 reversed MICALL2-induced angiogenesis. Therefore, MICALL2 facilitates CRC angiogenesis through the EGFR/PI3K/AKT/KLF5/VEGFA axis and may serve as a promising target for anti-angiogenic therapy."

Journal • Colorectal Cancer • Oncology • Solid Tumor • EGFR • KLF5

Ginkgetin attenuates oxidative stress-induced apoptosis and osteoarthritis progression via the PI3K/Akt signaling pathway-mediated upregulation of Bcl-2. (PubMed, J Ethnopharmacol) - "Ginkgetin impedes OA progression by activating the PI3K/Akt/Bcl-2 axis, which reduces oxidative stress and prevents chondrocyte apoptosis, underscoring the potential of ginkgetin as a therapeutic agent for OA."

IO biomarker • Journal • Immunology • Osteoarthritis • Pain • Rheumatology • BAX • BCL2

Anti-Parkinson's disease polysaccharide PFP50-1 attenuated neuroinflammation via inhibition of TLR4/NF-κB and PI3K/Akt pathways and suppression of NLRP3 inflammasome activation. (PubMed, Int J Biol Macromol) - "Subsequently, investigations revealed that TLR4 inhibitor (TAK242) and PI3K inhibitor (LY294002) significantly potentiated PFP50-1's inhibitory effects on LPS-induced pro-inflammatory mediators. Notably, PFP50-1 effectively ameliorated MPTP-induced dopaminergic (DA) neuronal degeneration in vivo, which was associated with the downregulation of the TLR4-mediated and PI3K-mediated signaling pathways, as well as the NLRP3 inflammasome. Collectively, our data indicated that PFP50-1's anti-neuroinflammation effect is related to downregulating the TLR4/NF-κB and PI3K/Akt signaling pathways and suppressing NLRP3 inflammasome activation, making it a promising candidate for PD."

Journal • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • IL18 • IL1B • MYD88 • NLRP3 • TLR4

CSF-Delivered miR-204-5p Enhances Post-Stroke Recovery via PI3K/Akt-Mediated Astrocyte Modulation (ISC 2026) - "Consistently, treatment with the PI3K/Akt inhibitor LY294002 produced similar reductions in GFAP expression...Immunofluorescence analysis of the peri-infarct area revealed a significant decrease in astrocytes and a corresponding increase in neurons in the mimic-treated group compared to vehicle.(Conclusion) Intrathecal administration of a miR-204-5p mimic promoted functional recovery by suppressing astrocyte activation through the PI3K/Akt signaling pathway. This approach holds promise as a potential exosome- or liposome-based therapeutic strategy for future clinical applications."

IO biomarker • Cardiovascular • Ischemic stroke • Solid Tumor • BCL2 • FAP • GFAP • MIR204

Insulin-like growth factor-1 enhances β-amyloid protein clearance in HMC3 microglia via low-density lipoprotein receptor-related protein 1-mediated pathway. (PubMed, Exp Cell Res) - "Importantly, treatment with LY294002, a PI3K inhibitor, significantly reduced the intracellular Aβ1-42 levels and decreased the expression of LRP1...Finally, we identified that IGF-1 promotes lysosomal proteolysis of Aβ1-42 by increasing cathepsin B (CTSB) and cathepsin D (CTSD) expression. Consequently, these results demonstrated that IGF-1 promotes the internalization and lysosomal degradation of Aβ by microglia, which is an effective approach to lowering brain Aβ levels, and it might be a promising therapeutic target for AD."

Journal • Alzheimer's Disease • CNS Disorders • Dyslipidemia • Targeted Protein Degradation • CTSB • CTSD • IGF1 • LRP1

Overexpression of IL7R Attenuates Cerebral Ischemia-Reperfusion Injury by Inhibiting Apoptosis. (PubMed, J Integr Neurosci) - "Overexpression of IL7R was shown to alleviate CIRI by suppressing apoptosis. These findings indicate IL7R as a novel target for IS treatment."

IO biomarker • Journal • B Cell Lymphoma • Cardiovascular • Ischemic stroke • Lymphoma • Oncology • Reperfusion Injury • BAX • CASP3 • IL7 • IL7R

FMDV VP3 Induces IL-10 Expression in Porcine Macrophages via PI3K Interaction and PI3K/AKT-mTOR Pathway Activation. (PubMed, Viruses) - "Mechanistically, VP3 promoted phosphorylation of PI3K, AKT, and mTOR; this effect was abolished by the PI3K inhibitor LY294002, which also abrogated VP3-induced IL-10 secretion (p < 0.05)...Co-IP and confocal microscopy confirmed direct binding of VP3 to PI3K in the cytoplasm. In conclusion, FMDV VP3 induces IL-10 overexpression by directly activating the PI3K/AKT-mTOR signaling pathway, thereby elucidating a key mechanism of FMDV-induced immunosuppression."

Journal • Preclinical • Infectious Disease • ATF1 • IL10

Ginseng Polysaccharides Protect Against Endoplasmic Reticulum Stress-Induced Damage via PI3K/Akt Signalling Pathway in Bovine Ovarian Granulosa Cells. (PubMed, Cells) - "Moreover, using the PI3K/Akt pathway inhibitor LY294002, we demonstrated that the inhibitor antagonized the effects of GPS, indicating that GPS promotes granulosa cell proliferation and restores estrogen secretion via activating the PI3K/Akt pathway. In vivo experiments further confirmed that GPS effectively attenuates ERS-induced ovarian damage in mice. Collectively, these findings reveal that GPS improves granulosa cell function and ovarian tissue integrity by modulating the ERS network and the PI3K/Akt pathway, yielding a theoretical basis for preventing follicular atresia and enhancing reproductive efficiency in cattle."

Journal

The protective role of CD44 and microRNA-146a in tendinopathy. (PubMed, Bone Joint Res) - "To dissect the CD44-AKT-miR-146a signalling pathway, the PI3K/AKT inhibitor LY294002 and the CD44 antagonizing antibody OX-50 were used...This study highlights the protective role of the CD44-AKT-miR-146a axis in tendinopathy. By modulating the AKT/miR-146a/Smad4 signalling pathway, CD44 and miR-146a effectively reduce apoptosis in tendinopathic tenocytes and tendons."

Journal • Immunology • Inflammation • Osteoarthritis • Pain • Rheumatology • CD44 • IL1B • MIR146A • SMAD4

GLP-2 alleviates postmenopausal osteoporosis by acting on osteoblasts through the PI3K/AKT/FOXO1 signalling pathway to downregulate FGF23 expression. (PubMed, J Orthop Surg Res) - "GLP-2 ameliorates postmenopausal osteoporosis by activating the PI3K/AKT/FOXO1 pathway in osteoblasts, leading to FGF23 downregulation. These findings provide novel molecular insights and potential therapeutic targets for the use of GLP-2 in osteoporosis management."

Journal • Osteoporosis • Rheumatology • FGF23 • FOXO1 • RUNX2

Baicalin Attenuates Ferroptosis after Subarachnoid Hemorrhage via the PI3K/AKT/GPX4 and NLRP3 Axis. (PubMed, Curr Neuropharmacol) - "Baicalin can alleviate ferroptosis after SAH by activating the PI3K/AKT pathway."

Journal • Cardiovascular • CNS Disorders • Hematological Disorders • Subarachnoid Hemorrhage • Vascular Neurology • GPX4 • NLRP3 • PACERR • PTGS2

Mechanisms of electroacupuncture at Foot Shaoyang meridian acupoints on inflammatory response in postmenopausal osteoporosis rats based on the PI3K/AKT signaling pathway (PubMed, Zhen Ci Yan Jiu) - "EA at Foot Shaoyang meridian acupoints can alleviate inflammatory responses and bone loss in postmenopausal osteoporosis rats, and its mechanism may be related to the activation of the PI3K/AKT pathway."

Journal • Preclinical • Inflammation • Oncology • Osteoporosis • Rheumatology • IL1B • IL6 • RUNX2 • TNFA • TRAP

Electroacupuncture improves diabetes-associated cognitive impairment in rats: potential involvement of hippocampal insulin receptor substrates 1/phosphatidylinositol 3-kinase/protein kinase B signaling pathway activation. (PubMed, Neuroreport) - "Electroacupuncture's mechanism may be involved in activating the IRS1/PI3K/AKT pathway, promoting the expression of GLUTs and MCTs, and regulating hippocampal energy metabolism."

Journal • Preclinical • Alzheimer's Disease • Cognitive Disorders • Diabetes • Metabolic Disorders • PIK3CG

Downregulation of OPCML is associated with activation of AKT signaling and aggressive phenotypes in glioblastoma cells. (PubMed, Front Oncol) - "Functional validation used a single OPCML small interfering RNA (siRNA) with a non-targeting siRNA control (siNC) in U87 and U251 cells with Transwell invasion, wound healing, colony formation, CCK-8 proliferation, and Western blotting for p-AKT and p-mTOR, with LY294002 rescue...Loss of OPCML aligns with proliferative programs and a GBM-specific immune pattern. These data nominate OPCML as a prognostic marker and a surface-level modulator that could be leveraged alongside RTK/PI3K axis inhibitors in GBM."

Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • OPCML

MTP18 as a prognostic biomarker and therapeutic target in lung adenocarcinoma. (PubMed, Respir Res) - "MTP18 functions as a novel oncogenic driver in LUAD by orchestrating a "fission-ROS-PI3K/AKT" signaling axis. Targeting MTP18-mediated mitochondrial dynamics offers a promising therapeutic strategy to disrupt both tumor growth and metabolic adaptation in LUAD."

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

Fibroblast growth factor 9 activates fibroblast activation and drives the progress of shoulder stiffness. (PubMed, Front Cell Dev Biol) - "LY294002 was used both in NIH3T3s and mouse SS models...Our findings revealed that FGF9 drove fibroblast activation and joint capsule fibrosis in SS via the PI3K/Akt signaling pathway. Targeted inhibition of the PI3K/Akt signaling might represent a promising therapeutic strategy for SS."

Journal • Fibrosis • Immunology • Inflammation • Inflammatory Arthritis • Pain • FGF

Integrating Network Pharmacology, Machine Learning, and Experimental Validation to Elucidate the Mechanism of Cardamonin in Treating Idiopathic Pulmonary Fibrosis. (PubMed, Int J Mol Sci) - "In vitro, CDN significantly mitigated fibrosis in bleomycin (BLM)-challenged A549 cells, downregulating the expression of α-smooth muscle actin (α-SMA) and fibronectin...Mechanistically, CDN significantly suppressed the IGF1/PI3K/AKT axis; this inhibitory effect was partially reversed by exogenous IGF1 supplementation and further enhanced by the PI3K-specific inhibitor LY294002...These findings lend support to a robust mechanistic basis for developing CDN as a potential therapeutic candidate for IPF. It should be noted that these conclusions are drawn from in vitro experiments using A549 cells, and further validation in primary alveolar epithelial cells and animal models is warranted to confirm their physiological relevance."

Journal • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • CDH1 • IGF1 • VIM

TRANSFORMING GROWTH FACTOR-Β1 ACTS VIA TΒR-I ON MICROGLIA TO PROTECT AGAINST MPP (ADPD 2026) - "These findings establish that TGF-β1 activates TβR-I and its down- stream p38 MAPK and PI3K–Akt signaling pathways in microglia to protect against DAergic neuronal loss that characterizes in PD."

CNS Disorders • Movement Disorders • Parkinson's Disease • ITGAM • TGFB1 • TNFA

Knockdown of programmed cell death 4 inhibits endoplasmic reticulum stress in male mice with intracerebral hemorrhage through the phosphoinositide 3-kinase/protein kinase B pathway. (PubMed, J Stroke Cerebrovasc Dis) - "Pdcd4 knockdown alleviates ICH through PI3K/AKT pathway-mediated ER stress."

Journal • Preclinical • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Inflammation • Vascular Neurology • PDCD4