LY294002 / Eli Lilly - LARVOL DELTA

Long non-coding RNA SNHG6 promotes odontoblastic differentiation of human dental pulp stem cells via the PI3K/Akt/mTOR pathway. (PubMed, Differentiation) - "Mechanistically, pathway inhibitors LY294002 and Rapamycin were used. Western blot analysis confirmed that SNHG6 promotes odontoblastic differentiation by activating the PI3K/Akt/mTOR signaling pathway, as shown by changes in phosphorylated Akt, mTOR, S6K1, and 4EBP1 levels. These findings highlight SNHG6 as a key regulator of hDPSC differentiation through PI3K/Akt/mTOR signaling, offering new insights into the molecular mechanisms controlling odontoblast formation."

Journal • EIF4EBP1

Nicotinamide adenine dinucleotide attenuates neuronal apoptosis in spinal cord ischemia-reperfusion injury via the activation of PI3K/AKT pathway. (PubMed, Eur J Pharmacol) - "Mechanistically, NAD+ restored phosphorylation levels of PI3K and AKT and favorably modulated apoptotic regulators-effects partially reversed by LY294002, confirming the critical role of the PI3K/AKT axis. These findings provide mechanistic evidence that exogenous NAD+ exerts acute neuroprotection during the early reperfusion phase, mediated through PI3K/AKT pathway activation and subsequent suppression of oxidative stress and apoptosis."

IO biomarker • Journal • Cardiovascular • Reperfusion Injury • BCL2 • CASP3

Mechanistic Insights into Anti-Melanogenic Effects of Fisetin: PKCα-Induced β-Catenin Degradation, ERK/MITF Inhibition, and Direct Tyrosinase Suppression. (PubMed, Int J Mol Sci) - "The proteasome inhibitor MG132 confirmed that fisetin accelerates β-catenin and MITF degradation. Additionally, inhibition of the PI3K/AKT pathway by LY294002 or the ERK pathway by PD98059 reversed fisetin's reduction of tyrosinase activity and melanin synthesis, further verifying the participation of these pathways. Computational docking integrated with deep learning-based CNN scoring revealed that fisetin interacts with PKCα, β-catenin, tyrosinase, and TYRP1. Collectively, these findings suggest that fisetin exerts multi-targeted inhibitory effects on melanogenesis, highlighting its potential as a therapeutic and cosmetic agent for hyperpigmentation."

Journal • Dermatology • Dermatopathology • Melanoma • Oncology • Solid Tumor • Targeted Protein Degradation • CTNNB1 • MITF • Tyrosinase • TYRP1

Dl-3-n-Butylphthalide Promotes Cortical Angiogenesis via Akt/GSK-3β Signaling in Ischemic Stroke Mice. (PubMed, CNS Neurosci Ther) - "In conclusion, NBP enhances recovery after ischemic stroke by promoting cortical angiogenesis and vasodilation through activation of the Akt/GSK-3β pathway. These findings highlight its therapeutic potential for delayed intervention in ischemic stroke."

Journal • Preclinical • Cardiovascular • Ischemic stroke • CD31 • GSK3B • PECAM1

TLR2-PI3K/Akt mediated microbe-mimetic priming boosts the therapeutic paracrine function of GelMA-Encapsulated MSCs for diabetic wound regeneration. (PubMed, Bioact Mater) - "Mechanistic studies confirmed the pivotal role of the TLR2-PI3K/Akt axis, as genetic (siRNA) or pharmacological (LY294002) inhibition abolished the enhanced therapeutic benefits of plMSCs. This study uncovers a microbiota-inspired priming strategy that reprograms MSC paracrine function and establishes a translational biohybrid platform (plMSC-GelMA). By harnessing microbial cues and biomaterial engineering, we offer a promising solution for enhancing stem cell therapy in refractory diabetic wound healing."

Journal • CD31 • IL10 • PECAM1 • TGFB1 • TLR2

Protective effects of quercetin, the key component of Zuo Gui Wan, against Alzheimer's disease via the PI3K/AKT pathway: insights from network pharmacology, molecular docking, and cell experiments (PubMed, Zhejiang Da Xue Xue Bao Yi Xue Ban) - "Quercetin, the key active ingredient of Zuo Gui Wan, exerts its protective effects against Alzheimer's disease by regulating the PI3K/AKT signaling pathway, inhibiting neuronal cell damage and apoptosis."

IO biomarker • Journal • Alzheimer's Disease • CNS Disorders • BCL2 • CASP3 • EGF

Xiangsha Liujunzi Decoction restores mitochondrial function and ameliorates chronic ulcerative colitis by regulating the PI3K/AKT/Nrf2 and AMPK/SIRT1/PGC-1α signaling pathways. (PubMed, J Ethnopharmacol) - "XS mitigates chronic UC by decreasing ROS levels and inhibiting the macrophage inflammatory response by regulating the PI3K/AKT/Nrf2 and AMPK/SIRT1/PGC-1α signaling pathways."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • IL1B • IL6 • NRF1 • OCLN • TFAM • TJP1 • TNFA

Vasodilatory effects of trans-3-methoxy-β-nitrostyrene, a synthetic nitroderivative, on rat thoracic aorta: involvement of soluble guanylate cyclase stimulation. (PubMed, J Cardiovasc Pharmacol) - "T3MN-induced vasodilatory effects remained unaffected by indomethacin, MDL-12,330A or glybenclamide but were significantly reduced by endothelium removal, L-NAME, ODQ, LY294002, TEA, 4-AP, and apamin. Under Ca2+-free conditions, T3MN was unresponsive to transient contractions evoked by caffeine, whereas it inhibited contractions induced by (i) the protein kinase C activator phorbol 12-myristate 13-acetate, (ii) the tyrosine phosphatase inhibitor sodium orthovanadate, (iii) exogenous calcium influx via receptor- or voltage-operated Ca2+ channels and (iv), in an ODQ-preventable manner, those evoked by PHE or Ca2+ influx through stores-operated Ca2+ channels activated by thapsigargin-induced Ca2+ store depletion. In conclusion, T3MN induced a potent vasorelaxant effect that seems to be mediated partly by an endothelium-dependent mechanism involving activation of the Akt/eNOS/NO pathway and partly by an endothelium-independent mechanism through activation of the sGC/cGMP/PKG..."

Journal • Preclinical • NOS3

Sodium butyrate attenuates early brain injury and neuronal apoptosis after subarachnoid hemorrhage in rats via GPR41/PI3K/Akt pathway. (PubMed, Neuroreport) - "These findings suggest that NaB may mitigate EBI after SAH by inhibiting neuronal apoptosis, with the underlying mechanism potentially involving activation of the GPR41/PI3K/Akt signaling pathway."

IO biomarker • Journal • Preclinical • Cardiovascular • CNS Disorders • Hematological Disorders • Ischemic stroke • Subarachnoid Hemorrhage • Vascular Neurology • BCL2

Sodium butyrate attenuates early brain injury and neuronal apoptosis after subarachnoid hemorrhage in rats via GPR41/PI3K/Akt pathway. (PubMed, Neuroreport) - "These findings suggest that NaB may mitigate EBI after SAH by inhibiting neuronal apoptosis, with the underlying mechanism potentially involving activation of the GPR41/PI3K/Akt signaling pathway."

IO biomarker • Journal • Preclinical • Cardiovascular • CNS Disorders • Hematological Disorders • Ischemic stroke • Subarachnoid Hemorrhage • Vascular Neurology • BCL2

Nicotine Activates PI3K/AKT Pathway to Induce Cellular Proliferation, Invasion, and Migration in HPV-16 Positive Cervical Cancer SiHa Cells. (PubMed, J Appl Toxicol) - "Critically, the use of a PI3K inhibitor (LY294002) demonstrated that the nicotine-induced downregulation of p53 and upregulation of MMP-2, as well as the enhancement of cellular invasion are dependent on PI3K/AKT pathway activation. These findings conclusively demonstrate that nicotine promotes the malignant transformation of HPV-16 positive cervical cancer cells by altering the expressions of MMP-2, p53, Caspase-3, and p21 via the activation of the PI3K/AKT pathway. This highlights the therapeutic potential of targeting this pathway in cervical cancer treatment."

Journal • Cervical Cancer • Oncology • Solid Tumor • CASP3 • CDKN1A • MMP2

Host angiogenic reprogramming by Echinococcus multilocularis protoscoleces protein via PDGFR/PI3K/AKT cascade. (PubMed, Front Microbiol) - "Interventions utilizing a range of inhibitors at the in vitro level, including the PDGFR-β inhibitor AG1296, the PI3K inhibitor LY294002, the AKT inhibitor MK2206, and the FAK inhibitor Y15, demonstrated that E. multilocularis protoscoleces protein (EmP) induces angiogenesis through PDGFR/PI3K/AKT/FAK signaling pathway. 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."

Journal • Infectious Disease • Oncology • PDGFRB

99mTc-HP-Ark2 SPECT/CT imaging reveals dynamic HER2 regulation in trastuzumab resistance and its reversal by PI3K inhibition. (PubMed, Int J Cancer) - "Treatment with the PI3K inhibitor LY294002 effectively inhibited p-PI3K activation and substantially reduced HER2 expression. Immunohistochemistry (IHC) analysis confirmed a strong positive correlation between changes in HER2 expression and tumor radioactive uptake trends. This study highlights the pivotal role of HER2 as a dynamic biomarker in trastuzumab resistance and supports the integration of molecular imaging into clinical decision-making for personalized therapeutic adjustments in HER2-positive breast cancer."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

AFP promotes cancer multidrug resistance through activating PI3K/Akt/NF-κB signaling pathway. (PubMed, Sci Rep) - "When these cancer cells were treated with doxorubicin (ADM) and 5-fluorouracil (5-FU), cell survival rate was determined by MTT, apoptosis by TUNEL, and colony formation by colony formation assay. The cancer cells were treated with the PI3K/Akt pathway inhibitor LY294002, and the expression of drug resistance-related proteins MDR1, MRP1, BCRP, Livin, cIAP1, XIAP, Akt, p-Akt, p65, and p-p65 was detected by Western blotting...AFP regulates the expression of drug resistance-related genes by activating the PI3K/Akt/NF-κB signaling pathway. AFP plays a pivotal role in MDR of cancer cells, the mechanism may be involved in activating the PI3K/Akt/NF-κB signaling pathway."

Journal • Cervical Cancer • Liver Cancer • Oncology • Solid Tumor • ABCB1 • AFP • XIAP

Gut-derived Helicobacter rodentium aggravates Tfh/Tfr imbalance and neuroinflammation via PI3K/AKT activation in anti-NMDAR encephalitis mice. (PubMed, Tissue Cell) - "Helicobacter rodentium exacerbates anti-NMDAR encephalitis by inducing PI3K/AKT-mediated Tfh/Tfr imbalance, highlighting a potential therapeutic target in autoimmune encephalitis."

Journal • Preclinical • CNS Disorders • Immunology • Inflammation • Oncology • IL10 • TNFA

Taraxasterol alleviates osteoporosis by targeting PI3K/AKT/PPARγ signaling axis to suppress necroptosis and reverse osteogenic-adipogenic differentiation imbalance in BMSCs. (PubMed, Phytomedicine) - "Our study reveals for the first time that TAX restores osteogenic-adipogenic equilibrium in OP-BMSCs and promotes bone regeneration through PI3K/AKT/PPARγ activation and mitochondrial protection-mediated suppression of necroptosis. These results position TAX as a promising therapeutic candidate for osteoporosis."

Journal • Oncology • Osteoporosis • Rheumatology • PPARG • TNFA

PLIN5 Promotes Lipid Reconstitution in Goat Intramuscular Fat via the PPARγ Signaling Pathway. (PubMed, Biology (Basel)) - "Rescue experiments with the PI3K-AKT inhibitor (LY294002) and the PPARγ inhibitor (GW9662) showed that the PI3K-AKT signaling pathway is involved in the regulation of cell proliferation, and PPARγ is involved in the regulation of lipid deposition. In conclusion, our findings demonstrate that PLIN5 regulates lipid reconstitution in goat intramuscular fat via PPARγ and PI3K-AKT signaling pathways. This regulation delivered theoretical support for improving meat quality from the aspect of IMF deposition."

Journal • PLIN2 • PPARG

Knockdown of GCNT2 promoted osteoblast differentiation by activating PI3K/AKT/mTOR pathway in osteoblasts. (PubMed, Sci Rep) - "ALP and ARS intensities, together with Runx2, OCN, and OPN expression elevated by GCNT2 knockdown, were attenuated by the PI3K inhibitor LY294002. Suppressed GCNT2 promoted osteoblast differentiation by activating PI3K/AKT/mTOR signaling pathway in OP. These in-vitro findings suggest that GCNT2 knockdown merits further pre-clinical evaluation as a potential therapeutic strategy for OP."

Journal • Metabolic Disorders • Osteoporosis • Rheumatology • RUNX2 • SPP1

FSTL1 silencing protects against lipopolysaccharide-induced ferroptosis in renal tubular cells by regulating the PI3K/Akt pathway. (PubMed, Peptides) - "The PI3K/Akt inhibitor LY294002 was used to validate the involvement of this pathway...FSTL1 mediates LPS-induced apoptosis, oxidative stress, and ferroptosis in renal tubular cells via the PI3K/Akt pathway. Targeting FSTL1-PI3K/Akt signaling may represent a novel approach to mitigate ferroptotic injury in endotoxin-stimulated renal tubular cells, providing mechanistic insights relevant to LPS-induced tubular injury model."

Journal • Acute Kidney Injury • Infectious Disease • Inflammation • Nephrology • Renal Disease • Septic Shock • ACSL4 • ANXA5 • FSTL1 • GPX4 • SLC7A11

Role of TRPV6-Mediated Calcium Signaling in High-Glucose-Inhibited Keratinocyte Migration. (PubMed, FASEB J) - "The calmodulin inhibitor W-7 or TFP suppressed the TRPV6 overexpression-induced increases in FN1 expression and cell migration, whereas the Akt inhibitor LY294002 or MK2206 restored the TRPV6 overexpression-induced increases in FN1 expression and cell migration to control levels in keratinocytes. Taken together, these results indicated that high glucose inhibits the expression of TRPV6 in keratinocytes, decreases Ca2+ flow into these cells, and decreases FN1 expression via Ca2+-calmodulin and Akt signaling to inhibit keratinocyte migration. Thus, TRPV6 may be a potential target for the development of novel treatments in diabetes-induced impaired wound healing."

Journal • Diabetes • Metabolic Disorders • FN1 • TRPV6

Thyrotropin-releasing hormone protects hippocampal neurons against glutamate toxicity via phosphatidylinositol 3-kinase/AKT pathway and new protein synthesis. (PubMed, bioRxiv) - "Instead, PI3K inhibitor LY294002 but not mitogen-activated protein kinase (MAPK)/Extracellular signal-regulated kinase (ERK)1/2 inhibitor U0126 completely inhibits the protective effect of TRH...In the present study we demonstrate that TRH neuroprotection is mediated via PI3K/AKT signaling pathway and new protein synthesis. This finding provides mechanistic support for the action of TRH in traumatic brain injury and other neurodegenerative diseases."

Journal • Alzheimer's Disease • CNS Disorders • Epilepsy • Vascular Neurology

Ginsenoside Rg1 alleviates HG-induced autophagy of retinal microvascular endothelial cells by activating ACE2/Ang1-7/Mas in vitro. (PubMed, Sci Rep) - "However, the regulatory effects of Rg1 on cell viability, ACE2/Ang1-7/Mas axis and autophagy were reversed in the presence of either A779 or LY294002. Rg1 alleviates HG-induced autophagy of HRMECs through the ACE2/Ang1-7/Mas axis, mediated by the PI3K/Akt pathway, supporting the protective effect of Rg1 on retinal endothelium."

Journal • Preclinical • Diabetes • Diabetic Retinopathy • Ophthalmology • Retinal Disorders • ANGPT1

Ethanol extract of Gastrodia elata Blume alleviates ischemic stroke by inhibiting oxidative stress and ferroptosis through the PI3K/AKT/Nrf2 pathway. (PubMed, J Ethnopharmacol) - "This study revealed for the first time that GEE can improve IS by regulating the PI3K/AKT pathway to activate Nrf2 and its downstream antioxidant and anti-ferroptotic effects."

Journal • Cardiovascular • CNS Disorders • Inflammation • Ischemic stroke • Vascular Neurology

Jun Ginger Extract Improves Cold-Induced Asthma by Inhibiting Airway Inflammation via PI3K/AKT Pathway. (PubMed, Food Sci Nutr) - "After the metabolomics analysis, network pharmacology prediction and molecular docking test were performed, the effect of JGAE in regulating the phosphatidylinositol 3'-kinase/protein kinase B (PI3K/Akt) pathway was explored and validated by the PI3K inhibitor LY294002 and activator 740Y-P...Network pharmacology and molecular docking results suggested that downregulating the PI3K/Akt pathway might be the key mechanism, which was validated by the PI3K inhibitor and activator. These findings indicate that JG is a potential dietary intervention for CA management by downregulating the PI3K/Akt pathway, and gingerols might be the main active component."

Journal • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • AQP1 • MUC5AC

Targeting the Osteopontin-regulated PI3K/AKT signaling pathway: A molecular approach to overcome drug resistance and metastasis in gastrointestinal tumors. (PubMed, World J Gastrointest Oncol) - "OPN enhances tumor proliferation and survival through mechanistic target of rapamycin and B-cell lymphoma 2 upregulation (e.g., via denticleless E3 ubiquitin protein ligase homolog in hepatocellular carcinoma) and drives metastasis via PI3K/AKT-mediated epithelial-mesenchymal transition and androgen receptor (AR) activation (e.g., via the OPN-RAN-AR axis in pancreatic cancer)...Therapies targeting the OPN-PI3K/AKT axis (e.g., PI3K inhibitors like LY294002) or combination treatments (e.g., with EGFR-TKIs) show promise for reversing drug resistance. Future research should focus on OPN isoform specificity, clinical translation, and interactions with autophagy and long non-coding RNAs to refine precision therapies. This review summarizes recent advances in understanding the molecular mechanisms, therapeutic targets, and clinical challenges of the OPN-PI3K/AKT axis in gastrointestinal tumors, providing a foundation for overcoming resistance and developing precision therapies."

Journal • Review • B Cell Lymphoma • Colorectal Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Lymphoma • Oncology • Pancreatic Cancer • Solid Tumor • Targeted Protein Degradation • AR • BCL2 • CXCR3 • mTOR • SPP1 • TLR4 • UBE2H • UBR5 • XIAP