LY294002 / Eli Lilly - LARVOL DELTA

Matrine Alleviates Atherosclerosis by Targeting REG1A and Activating the PI3K/AKT/mTOR Pathway to Inhibit Endothelial Cell Ferroptosis. (PubMed, Biochem Genet) - "In addition, both LY294002 (an inhibitor of the PI3K signaling) and Erastin (an inducer of ferroptosis) reversed the alleviation of matrine treatment on ferroptosis in ox-LDL treated HUVECs. The results in vivo showed that matrine treatment inhibited high-fat diet-induced aortic ferroptosis in ApoE-/- mice and alleviated arterial tissue lesions. In summary, matrine inhibits ferroptosis by targeting REG1A to activate PI3K/Akt/mTOR pathway, thereby alleviating aortic endothelial injury and lipid plaque formation in AS mice, suggesting that matrine has potential value for the treatment of AS."

Journal • Atherosclerosis • Cardiovascular • Oncology • APOE • REG1A

TGFBI promotes EMT and perineural invasion of pancreatic cancer via PI3K/AKT pathway. (PubMed, Med Oncol) - "Moreover, PI3K inhibitor LY294002 was observed to counteract the effects of TGFBI on neural invasion, and EMT in Capan-2 and CFPAC-1...Finally, we confirmed TGFBI as potential biomarker for PNI and prognosis of pancreatic cancer. Collectively, we concluded that TGFBI activates the PI3K-AKT pathway in pancreatic cancer cells, ultimately promoting EMT and leading to PNI."

Journal • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • TGFBI

A Dendrobium chrysotoxum extract erianin induce AML cells death by activating PPARɑ and downregulating PI3K/AKT signaling pathways. (PubMed, Toxicon) - "Notably, erianin revealed vigoroso coordinate repression with LY294002 on AML cells. Our findings indicate that erianin showed a potent cytotoxic effect on AML cells and affected AML cells via PPARɑ to regulate PI3K/AKT signaling pathways. We demonstrated the potent anti-AML effects of erianin and reported its potential mechanisms of action, indicating its potential for further development as a novel anti-AML drug."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CDKN1A • PIK3R1

Sevoflurane Preconditioning Protects Against Myocardial Ischemia Reperfusion Injury in Mice via PI3K/AKT/GSK3β-mediated Upregulation of Syntaxin1a. (PubMed, J Biochem Mol Toxicol) - "Preconditioning with volatile anesthetics, such as isoflurane and sevoflurane, can protect the myocardium against ischemia/reperfusion injury (IRI)...Regulation of signaling pathway by intraperitoneal administration of the phosphatidylinositol 3-kinase (PI3K) inhibitor, Ly294002 (30 mg/kg), and GSK3β inhibitor, TWS119 (30 mg/kg)...TWS119 causes the opposite effect (p < 0.05). These findings demonstrated that SPC activated the AKT/GSK3β signaling pathway to upregulate Stx1A expression and provide protection to the myocardium."

Journal • Preclinical • Anesthesia • Cardiovascular • Myocardial Infarction • Myocardial Ischemia • Oncology • Reperfusion Injury • Solid Tumor • Targeted Protein Degradation • Thymoma • Thymus Cancer • GSK3B • NPPB

P2X7 receptor promotes the growth and metastasis of gastric cancer by activating P13/AKT/GSK-3 beta signaling (experimental research). (PubMed, Int J Surg) - "Our conclusion is that activation of P2X7R promotes the proliferation, metastasis and EMT of GC cells by activating P13/AKT/GSK-3beta signaling, and indicates that P2X7R may become a new potential target for GC treatment."

Journal • Gastric Cancer • Oncology • Solid Tumor • CDH1 • CDH2 • GSK3B • MMP2 • MMP9 • VIM • ZEB1

Effect of TNF-α on cisplatin-induced permeability change of blood labyrinth barrier in cochlea of C57BL/6J mice (PubMed, Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi) - "The expression of MMP-9 decreased in PC+TNF-α+LY294002 group (P<0.05). The hearing loss of C57BL/6J male mice induced by cisplatin may be related to the increased release of TNF-α from the blood labyrinth barrier EC in the cochlear stria vascularis, and the activation of PI3K/AKT signaling pathway by TNF-α in PC, which increases the secretion of MMP-9 from PC, ultimately leads to the increased permeability of the blood labyrinth barrier."

Journal • Preclinical • Oncology • Otorhinolaryngology • CDH5 • MMP2 • MMP9 • TJP1 • TNFA

Nobiletin alleviates brain injury in uremic mice and inhibits indoxyl sulfate-induced neurotoxicity in HT22 cells through the phosphatidylinositol 3-kinase/protein kinase B signaling pathway. (PubMed, Cytojournal) - "A uremic encephalopathy mouse model was established by inducing renal failure with cisplatin (DDP)...The PI3K inhibitor LY294002 was used to further investigate the involvement of the PI3K/Akt pathway in the neuroprotective effects of NOB...NOB exerts potent neuroprotective effects by activating the PI3K/Akt pathway, mitigating uremia-induced brain injury and preventing DDP-induced neurotoxicity. These findings support the potential therapeutic application of NOB for uremic encephalopathy and provide insights into its underlying mechanisms."

Journal • Preclinical • Chronic Kidney Disease • CNS Disorders • Nephrology • Renal Disease • Vascular Neurology

CIAPIN1 attenuates ferroptosis via regulating PI3K/AKT pathway in LPS-induced podocytes. (PubMed, BMC Nephrol) - "These results suggest that serum CIAPIN1 inhibits LPS-induced ferroptosis in podocytes by regulating the PI3K/AKT signaling pathway."

Journal • Acute Kidney Injury • Infectious Disease • Nephrology • Renal Disease • Septic Shock • GPX4 • SLC7A11

TFEB nuclear persistence predicts sensitivity to lysosomal inhibition in therapy-induced senescent thyroid cancer cells (AACR 2025) - "To assess whether lysosomes may be a valid target for new senotherapies, we employed as a TIS model different cell lines of anaplastic thyroid cancer, an aggressive and untreatable type of tumor, undergoing senescence upon either CDK4/6 inhibitor Palbociclib or ionizing radiation treatment...Conversely, the lysosome-sparing autophagy inhibitor LY294002 did not replicate these results, suggesting that the senolytic effect is ascribable to lysosomal rather than autophagy inhibition...Interestingly, this was associated with significantly lower protein levels of Exportin-1, an export receptor responsible for TFEB nuclear extrusion.Our results indicate that lysosomes represent a promising target for developing new senotherapeutics, but TFEB's ability to enter and persist at the nuclear level appears to be crucial in determining this sensitivity. Understanding the molecular differences underlying the varying functionality of the lysosomal biogenesis machinery, often..."

IO biomarker • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • CDKN1A • HMGA2 • TFEB • XPO1

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

Intelectin-1 promotes granulosa cells proliferation and modulates apoptosis via ERK1/2, AKT, and insulin receptor signaling pathways in Large White and Meishan pigs. (PubMed, Gen Comp Endocrinol) - "Then, using pharmacological inhibitors of ERK1/2 (PD98059, 5 μM), AKT (LY294002, 10 μM) and INSR (1 μM), treated alone or with ITLN1 (S961, 50 ng/mL), we analyzed its involvement in the effects of ITLN1 on Gc proliferation/apoptosis. We demonstrated that ITLN1 had a mitogenic effect on Gc by enhancing cell cycle progression and modulating the levels of PCNA, cyclins and apoptotic factors via ERK1/2, AKT, and INSR, suggesting that ITLN1 is a newly identified regulator in ovarian folliculogenesis, regardless of the fatness degree of pigs."

IO biomarker • Journal • AMPK • BCL2 • CASP9 • FADD • IR • PCNA • STAT3 • XIAP

Inhibition of the Sp1/PI3K/AKT signaling pathway exacerbates doxorubicin-induced cardiomyopathy. (PubMed, Biochim Biophys Acta Mol Cell Res) - "Doxorubicin induces cardiotoxicity by promoting oxidative stress and apoptosis through the downregulation of the Sp1/PI3K/AKT signaling pathway. Inhibition of this pathway exacerbates cardiac injury, suggesting that targeting Sp1 and PI3K/AKT may offer novel therapeutic strategies for the prevention and treatment of DIC."

Journal • Cardiomyopathy • Cardiovascular • CASP3 • SP1

Fucoxanthin alleviates secondary brain injury in mice following intracerebral hemorrhage via PI3K-mediated inhibition of NF-κB signaling pathway. (PubMed, Pathol Res Pract) - "Fucoxanthin alleviates ICH-induced neurological deficits and brain injuries by suppressing the PI3K/Akt-mediated NF-κB pathway to inhibit M1 polarization and attenuate neuroinflammation, neuronal apoptosis, BBB dysfunction, and brain edema."

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

Glycoside components promote endothelial progenitor cell-derived exosomes repairing damaged vascular endothelium via the PI3K/AKT signaling pathway. (PubMed, Phytomedicine) - "The combination of AAP and EPC-Exo synergistically promotes vascular endothelial repair and angiogenesis, partly by enhancing EPC-Exo uptake through activation of the PI3K/AKT signaling pathway."

Journal • CASP3

Remote Ischemic Postconditioning Improve Cerebral Ischemia-Reperfusion Injury Induced Cognitive Dysfunction through Suppressing Mitochondrial Apoptosis in Hippocampus via TK/BK/B2R-Mediated PI3K/AKT. (PubMed, Mol Neurobiol) - "HOE140 was used to antagonize the bradykinin 2 receptor (B2R)...Finally, the PI3K inhibitor LY294002 reversed the anti-apoptotic effect induced by BK/B2R...In conclusion, RIPostC represents a promising therapeutic strategy for combating cognitive dysfunction by inhibiting cell apoptosis in hippocampus. Moreover, our results suggest that RIPostC may have a broader protective effect against apoptosis in other ischemia-reperfusion-related diseases."

IO biomarker • Journal • Alzheimer's Disease • Cardiovascular • Cognitive Disorders • Ischemic stroke • Reperfusion Injury • ANXA5 • BCL2 • CASP3 • CASP9

PTK2B inhibitor PF-431396 inhibits inflammatory response and apoptosis of ovarian granulosa cells by targeting AKT1 phosphorylation in premature ovarian insufficiency. (PubMed, Int Immunopharmacol) - "In this study, a rat POI model was established by intraperitoneal injection of cyclophosphamide (Cy) for 14 days...PF-431396 facilitated AKT1 phosphorylation, and the inhibitory effects of PF-431396 on GC inflammatory response and apoptosis were reversed by an AKT1 inhibitor LY294002...Additionally, it could improve Cy-induced ovarian tissue injury, inhibit inflammation and apoptosis, and elevate p-AKT1 level in ovarian tissues. Together, our results unveil that PF-431396, a PTK2B inhibitor, ameliorates ovarian dysfunction in POI through promoting AKT1 phosphorylation, suggesting that PTK2B may be a therapeutic target for POI."

Journal • Inflammation • Women's Health • PTK2B • TYK2

F-box/WD Repeat-Containing Protein 5 Promotes Breast Cancer Progression by Regulating Ferroptosis via Enhancing Krüppel-like Factor 13 Ubiquitination Through Phosphoinositide 3-Kinase/Serine/Threonine Protein Kinase Pathway. (PubMed, Rejuvenation Res) - "KLF13 silencing counteracted the inhibitory effects of FBXW5 depletion on cell proliferation, migration, and invasion, as well as its promotion of ferroptosis, effects that were reversed by LY294002. In conclusion, targeting FBXW5 may serve as a potential therapeutic strategy for BC by modulating the KLF13/PI3K/AKT axis."

Journal • Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • BRCA • WDR5

SIRT5 Regulates Lipid Deposition in Goat Preadipocytes via PI3K-Akt and MAPK Signaling Pathways. (PubMed, Animals (Basel)) - "Notably, we successfully reversed the phenotypic effects observed in SIRT5 knockdown goat precursor adipocytes by inhibiting the PI3K-Akt and MAPK signaling pathways using the AKT inhibitor LY294002 and the p38 MAPK pathway inhibitor PD169316, respectively. In conclusion, our findings demonstrated that SIRT5 may modulate intramuscular fat deposition in goats through PI3k-Akt and MAPK signaling pathways. These results expand the gene regulatory network associated with IMF formation and provide a theoretical foundation for improving meat quality by targeting IMF deposition."

Journal • Metabolic Disorders • HIF1A • SIRT5

Effect of Cu(ATSM) on the expression and activity of ABC export proteins in killifish (Fundulus heteroclitus) kidney tubules. (PubMed, Environ Toxicol Pharmacol) - "Cu(ATSM)-induced activation was further suppressed by phosphatidylinositol 3-kinase inhibitor LY-294002 and mTOR inhibitor rapamycin. Activation was also inhibited by GSK650394, an inhibitor of serum-and-glucocorticoid-inducible-kinase-1 being a subsequent target. Given the parallelism with other metals, this ABC transporter regulation appears to be a general defense mechanism of teleosts to react on metallic pollutants."

Journal

Chelidonine inhibits melanoma cell malignancy by inactivating TLR4/NF-κB and PI3K/AKT signaling pathways. (PubMed, Korean J Physiol Pharmacol) - "Furthermore, TAK-242 or LY294002 further enhanced the inhibitory effects chelidonine of on malignant cell behavior. In conclusion, our findings demonstrate that chelidonine effectively suppresses the malignancy of melanoma cells through the inhibition of TLR4/NF-κB and PI3K/AKT signaling pathways, suggesting its potential as a promising therapeutic agent for melanoma treatment."

Journal • Melanoma • Oncology • Solid Tumor • TLR4

Pterostilbene Potentiates the NGF-TrkA Signaling Pathway, Enhancing Differentiation in PC12 Cells. (PubMed, J Agric Food Chem) - "The selective inhibitors of TrkA (K252a) and PI3K/Akt (LY294002) were applied to validate the NGF/TrkA/Akt signaling pathways leading to diminished neurite outgrowth and reduced expression of neurofilaments in cells treated with pterostilbene and NGF. Taken together, the results indicate that pterostilbene could potentiate NGF/TrkA activity, enhancing neuron-like differentiation in PC12 cells under a low concentration of NGF. These findings suggest that the application of pterostilbene could be a promising alternative therapeutic strategy to improve NGF efficacy."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • NGF

L-Theanine attenuates oxidative damage induced by heat stress through the PI3K/AKT/Nrf2 signaling pathway in skeletal muscle cells. (PubMed, Poult Sci) - "The protective effects of LTA in HS-treated cultured cells were significantly reduced by the PI3K inhibitor LY294002 or the Nrf2 inhibitor ML385. In conclusion, our study showed that LTA protects cultured skeletal muscle cells from HS-induced oxidative damage by modulating the PI3K/AKT/Nrf2 signaling pathway, positioning LTA as a promising natural antioxidant for poultry feed additives aimed at improving muscle health."

Journal

Electroacupuncture modulates the gut-brain axis via the PI3K/Akt pathway to improve feeding behavior, body weight, glucolipid metabolism, and reduce insulin resistance in T2DM rats. (PubMed, Diabetol Metab Syndr) - "EA plays a role in managing feeding behavior, body weight, and glucolipid metabolism, as well as alleviating IR in T2DM rats. EA may contribute to the preservation of intestinal mucosal barrier integrity, likely through anti-inflammatory and anti-apoptotic actions mediated by the PI3K/Akt pathway. Additionally, EA appears to influence the regulation of brain-gut peptides and promote a healthier gut microbiota composition. These findings suggest that EA holds potential as an therapeutic approach for T2DM, with its mechanisms potentially linked to the modulation of the gut-brain axis via the PI3K/Akt pathway. Further research is warranted to fully elucidate these effects and their clinical implications."

Journal • Preclinical • Diabetes • Inflammation • Inflammatory Bowel Disease • Metabolic Disorders • Type 2 Diabetes Mellitus • CLDN1 • OCLN • TJP1

Triphenyl phosphate induces lipid metabolism disorder and promotes obesity through PI3K/AKT signaling pathway. (PubMed, Environ Int) - "Further research showed that TPHP activated the PI3K/AKT pathway, and PI3K inhibitor (LY294002) could rescue TPHP induced lipid droplet formation and normalize the expression of adipogenic markers. These findings confirm that TPHP is a potential environmental obesogen that can disrupt the metabolic homeostasis of white adipose tissue through the PPARγ and PI3K/AKT signaling pathways, with higher susceptibility in males. This study provides compelling evidence for the obesogenic effects of TPHP and information for risk assessment of organophosphorus flame retardants."

Journal • Dyslipidemia • Genetic Disorders • Metabolic Disorders • Obesity • PPARG

Edaravone Alleviates BV-2 Microglia-Mediated Neuroinflammation Through the PI3K/AKT/ NF-κB Pathway. (PubMed, Adv Biol (Weinh)) - "Additionally, the PI3K pathway inhibitor LY294002 and a PI3K overexpression plasmid are introduced to further analyze the expression changes of these markers. The results suggest that EDA may alleviate the inflammatory response mediated by activated MG through the PI3K/Akt signaling pathway."

Journal • Cardiovascular • CNS Disorders • Inflammation • Ischemic stroke