LY294002 / Eli Lilly - LARVOL DELTA

Kdf1 Regulates Molar Cusp Morphogenesis via the PI3K/AKT/mTOR Signalling Axis. (PubMed, Cell Prolif) - "Furthermore, in utero microcapillary injection of the PI3K/AKT/mTOR pathway inhibitor LY294002 partially rescued the molar cusp defects in K14-Cre;Kdf1fl/fl mice. Collectively, our findings provide in vivo evidence supporting the regulatory role of Kdf1 in molar cusp morphogenesis, highlighting its function in modulating dental epithelial cell proliferation via the PI3K/AKT/mTOR signalling pathway."

Journal

Phosphoinositide Signaling and Actin Polymerization Are Critical for Tip Growth in the Marine Red Alga Pyropia yezoensis. (PubMed, Plants (Basel)) - "Treatment with LY294002 and U73122, specific inhibitors of phosphoinositide-phosphate 3-kinase and phospholipase C, respectively, reduced side-branch formation and inhibited the elongation of branches...As CCB and LAT-B affect actin polymerization through different mechanisms, this result suggests differences in the contributions of actin polymerization to branch initiation versus tip growth. These findings demonstrate the critical and diverse functional roles played by phosphoinositide turnover and actin polymerization in the regulation of the initiation and maintenance of tip growth in the conchocelis phase of P. yezoensis."

Journal

CIAPIN1 promotes survival, proliferation, migration and glycolysis of endometrial cancer cells through PI3K/Akt pathway. (PubMed, Sci Rep) - "PI3K inhibition (LY294002) reversed these effects, confirming the pathway dependency. These findings highlight CIAPIN1 as a potential oncogenic driver in EC, enhancing tumor progression through PI3K/Akt-mediated glycolysis and oxidative stress modulation. Targeting CIAPIN1 may represent a novel therapeutic strategy for EC."

Journal • Endometrial Cancer • Oncology • Solid Tumor • CAT • LDHA • PKM

Molecular Mechanisms of Aminoglycoside-Induced Ototoxicity in Murine Auditory Cells: Implications for Otoprotective Drug Development. (PubMed, Int J Mol Sci) - "Co-treatment with PI3K inhibitors (LY294002, wortmannin) further suppressed Akt phosphorylation, supporting the role of PI3K-Akt signaling in auditory cells...Sodium thiosulfate (STS) and N-acetylcysteine (NAC) significantly decreased GTTR uptake, suggesting a protective effect against gentamicin-induced hair cell damage...Additionally, GTTR may be a simple, effective method for evaluating protective interventions in auditory cell lines. Overall, this study provides molecular-level insights into aminoglycoside-induced ototoxicity and introduces a platform for protective strategies."

Journal • Preclinical • Infectious Disease • Otorhinolaryngology • CASP3 • HSPA5 • SLC22A2

Inhibitory Effects of Vandetanib on Catecholamine Synthesis in Rat Pheochromocytoma PC12 Cells. (PubMed, Int J Mol Sci) - "Recently, TKIs, namely, sunitinib and selpercatinib, which were clinically used to target PPGLs, have been reported to decrease catecholamine levels without reducing tumor size. Moreover, both an MEK inhibitor U0126 and a PI3K/AKT inhibitor LY294002 suppressed catecholamine synthesis without decreasing viable cells. This study in rat pheochromocytoma PC12 cells reveals the direct inhibitory effects of vandetanib on catecholamine synthesis via the suppression of RET-ERK and RET-AKT signaling."

Journal • Preclinical • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • RET

Protective mechanism of moslosooflavone against hypobaric hypoxia-induced brain injury: insights from network pharmacology and in vivo validation. (PubMed, Eur J Pharmacol) - "Additionally, the beneficial effects of moslosooflavone, including reducing pathological damage and exerting antioxidant, anti-inflammatory, and antiapoptotic effects, were significantly attenuated by LY294002. These findings suggest that the modulation of the PI3K/AKT signaling pathway is a key mechanism underlying the protective effects of moslosooflavone against HHBI."

Journal • Preclinical • CNS Disorders • Vascular Neurology • CDC37 • HIF1A

Puerarin alleviates cerebral ischemia/reperfusion (CIR)-induced neurocyte oxidative stress and apoptosis via DNA demethylation-mediated PI3K/Akt activation. (PubMed, Phytomedicine) - "Pue inhibits DNMT3A/B activation, leading to demethylation of the PI3K promoter and subsequent activation of PI3K/Akt signaling, which mitigates CIR-induced oxidative stress and apoptosis. This study elucidates a novel epigenetic mechanism underlying Pue's neuroprotective effects and highlights its therapeutic potential for ischemic stroke treatment."

Journal • Cardiovascular • CNS Disorders • Cognitive Disorders • Ischemic stroke • Metabolic Disorders • Reperfusion Injury • ANXA5 • DNMT3A

GAS1 affects proliferation, apoptosis, and steroid hormone levels by regulating mitochondrial functions and the PI3K/AKT pathway in bovine granulosa cells. (PubMed, Theriogenology) - "In addition, the inhibition of GAS1 increased the level of phosphorylated PI3K/AKT, and LY294002, a PI3K/AKT pathway inhibitor, alleviated the effects of GAS1 inhibition on P4 and E2 levels in bovine granulosa cells. These results showed that GSA1 affects proliferation, apoptosis, mitochondrial function, and redox homeostasis and regulates P4 and E2 levels via the PI3K/AKT pathway in bovine granulosa cells. These results are helpful for analyzing the molecular mechanism of follicle development and provide a theoretical basis for improving follicle development and female animal fertility."

Journal • CYP19A1 • GAS1 • HSD3B1 • MFN2 • STAR

Exploring the comorbidity mechanisms of ITGB2 in rheumatoid arthritis and membranous nephropathy through integrated bioinformatics analysis. (PubMed, Ren Fail) - "Small molecules targeting ITGB2, including LY-294002 and CP466722, may serve as potential drugs for both RA and MN. As the pathogenic gene shared by both RA and MN, ITGB2 may play a role in M1 macrophage polarization and contribute to the maturation and differentiation of B cells through BAFF signaling."

Journal • Glomerulonephritis • Immunology • Inflammatory Arthritis • Nephrology • Renal Disease • Rheumatoid Arthritis • Rheumatology • ITGB2

2-Hydroxy-3-Methylanthraquinone Suppresses Hepatocellular Carcinoma Progression by Blocking Annexin A5-Mediated Phosphatidylinositol 3-Kinase/Protein Kinase B Signaling. (PubMed, Chem Biol Drug Des) - "These reversal effects were abolished by treatment with LY294002, a selective PI3K inhibitor. In summary, HMA suppresses the progression of HCC by targeting ANXA5 and inhibiting the PI3K/AKT signaling pathway, highlighting its potential as a novel therapeutic agent for HCC."

Journal • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • ANXA5

Estrogen protects against postpartum Concanavalin A-induced hepatitis by promoting intrahepatic CD4⁺CD25⁺ Treg expansion through activation of the PI3K/Akt signaling pathway in HBV-Tg mice. (PubMed, Virol J) - "Estrogen protects against postpartum Con A-induced hepatitis by promoting intrahepatic CD4⁺CD25⁺ Treg expansion through activation of the PI3K/Akt signaling pathway in HBV-Tg mice."

Journal • Preclinical • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Liver Failure • CD4 • CD8 • FOXP3 • IFNG • IL10 • IL2RA • ISG20 • TNFA

Astragaloside IV Alleviates H2O2-Induced Mitochondrial Dysfunction and Inhibits Mitophagy Via PI3K/AKT/mTOR Pathway. (PubMed, Cardiovasc Ther) - "However, cotreatment with LY294002 diminished the upregulation of PI3K, p-AKT, and p-mTOR induced by As-IV. In the study, we demonstrated that As-IV protected H9c2 cells from H2O2-induced mitochondrial dysfunction by inhibiting mitophagy, which might be related to the PI3K/AKT/mTOR pathway."

Journal • Cardiovascular • Metabolic Disorders • PINK1

Lysimachia christinae Hance aqueous extract ameliorates renal injury in kidney stone rats and calcium oxalate crystal-induced oxidative stress in HK-2 cells via inhibiting the PI3K/Akt/mTOR pathway. (PubMed, Histol Histopathol) - "This study shows that LCH ameliorates the kidney damage in kidney stone rats and HK-2 cells. The mechanism of LCH in treating kidney stones is related to the activation of the Nrf2/HO-1 axis and the inhibition of the PI3K/Akt/mTOR pathway."

Journal • Preclinical • Nephrology • Renal Calculi • Renal Disease

Astragaloside IV Promotes Osteogenic Differentiation of Periodontal Ligament Stem Cells via Activating PI3K/AKT/eNOS/NO Signaling Pathway: In vitro and in vivo Study. (PubMed, Drug Des Devel Ther) - "After treating the cells with different doses of AS-IV, LY294002 (PI3K inhibitor), and L-NAME (eNOS inhibitor), alkaline phosphatase (ALP) staining, alizarin red staining, qRT-PCR, Western blotting, nitric oxide (NO) assay and immunofluorescence staining were utilized to ascertain the expression level of related factors and the validity of PI3K/AKT/eNOS/NO pathway...AS-IV can promote the osteogenic differentiation of PDLSCs, and PI3K/AKT/eNOS/NO was involved. Meanwhile, AS-IV exhibits positive effects on tension-side osteogenesis during tooth movement in rats."

Journal • Preclinical • CD34 • NOS3 • PTPRC • THY1

Tamibarotene promotes differentiation of neuroblastoma SH-SY5Y cells into neurons, which is associated with activation of the PI3K/AKT signaling pathway. (PubMed, BMC Neurosci) - "Tamibarotene, a synthetic retinoid used in the treatment of acute promyelocytic leukemia, has been reported to induce differentiation in the SH-SY5Y cell line into neurons. Inhibition of the PI3K/Akt signaling pathway using LY294002 resulted in a decreased efficacy of AM80-induced differentiation in SH-SY5Y cells, along with downregulation of neuronal marker expression. These findings suggest that Am80 can effectively promote the differentiation of SH-SY5Y cells into neurons and reduce the proliferation of neuroblastoma cells, which is related to the PI3K/AKT pathway, providing a good model for the study of nervous system diseases."

Journal • Acute Promyelocytic Leukemia • Hematological Malignancies • Leukemia • Neuroblastoma • Oncology • Solid Tumor • CNR1 • CXCR4 • NTRK2

Bim and Mcl-1 Coordinate NVP-BEZ235-induced Renal Cell Carcinoma Cell Apoptosis. (PubMed, Arch Biochem Biophys) - "Bcl-2 inhibitor ABT-737 and Mcl-1 inhibitor AZD5991 predisposed NVP-BEZ235-treated cells to transform into the apoptotic phenotype. PI3K inhibitor LY294002 and Stat3 inhibitor AG490 duplicated the sensitized actions towards NVP-BEZ235...Data of in vivo tumor-bearing studies further revealed a better anti-tumor potential in the combination treatment of NVP-BEZ235 and MEK/ERK inhibitors without obvious toxicity. Our findings suggest that the feedback activation of pro-survival machinery is likely to be the main cause of cancer cells being refractory to NVP-BEZ235, and a combination treatment is a feasible strategy to sensitize cancer cell responses."

IO biomarker • Journal • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Targeted Protein Degradation • BCL2L11 • MCL1

Dexmedetomidine mitigates oxidative stress in H9C2 cardiac myoblasts under a high‑glucose environment via the PI3K/AKT signaling pathway. (PubMed, Mol Med Rep) - "H9C2 cardiac myoblasts were either untreated or pretreated with 10 nM Dex and the PI3K inhibitor LY294002 before exposure to H2O2 to induce oxidative cellular damage in the presence of HG culture medium. The present study revealed that Dex pretreatment attenuated H9C2 cardiac myoblast injury via the PI3K/AKT signaling pathway under HG conditions. Its protective effects may be achieved by reducing oxidative stress damage to cardiac myoblasts."

Journal • Anesthesia • Cardiovascular • Critical care • Diabetes • BAX • BCL2 • CASP3 • CAT

FGF21 restores metabolic function in Alzheimer's disease via activation of PI3K/Akt signaling. (PubMed, Neurol Res) - "The involvement of the PI3K/Akt/mTOR pathway was explored using the PI3K inhibitor LY294002...Conversely, FGF21 overexpression activated PI3K/Akt signaling, suppressed neuronal apoptosis, and restored metabolic functions in AD models. FGF21 alleviates AD-related cognitive impairment and restores metabolic function by activating the PI3K/Akt pathway."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Metabolic Disorders • FGF21

CXCR4/CXCL12 axis promotes lymphatic metastasis in tongue squamous cell carcinoma via PI3K/AKT signaling pathway. (PubMed, J Transl Med) - "The CXCR4/CXCL12 axis functions as a crucial mediator of TSCC lymphatic metastasis by promoting tumor cell invasiveness and lymphangiogenesis via the PI3K/AKT pathway. CXCR4 and CXCL12 serve as independent prognostic biomarkers for TSCC lymphatic metastasis and represent promising therapeutic targets for this aggressive malignancy."

Journal • Oncology • Squamous Cell Carcinoma • Tongue Carcinoma • CXCL12

Effect of Bazi Bushen Capsule on D-Galactose-Induced Human Endothelial Cell Senescence Through PI3K/Akt/eNOS Signaling Pathway. (PubMed, Aging Med (Milton)) - "The experimental groups comprised the following: Control, Model, and groups treated with drug-containing serum at low (BZBSL), medium (BZBSM), and high (BZBSH) doses of BZBS, in addition to a pathway inhibitor group (LY294002 [5 μM/L])...Compared to the Model group, drug-containing serum of BZBS significantly increased the expression levels of PI3K, p-Akt, Akt, and eNOS (p < 0.010) and elevated NO levels in the cells (p < 0.010), by which BZBS ameliorated HBMECs aging and enhanced the function of aging HBMECs. Our findings indicate that BZBS can mitigate D-gal-induced aging in HBMECs by activating the PI3K/Akt/eNOS signaling pathway."

Journal • NOS3

Ginsenoside Re ameliorates thioacetamide-induced acute liver injury through inhibiting autophagy-NLRP3 inflammasome pathway. (PubMed, Front Pharmacol) - "Additionally, the phosphoinositide 3-kinases (PI3K) inhibitor LY294002 and the mammalian target of rapamycin (mTOR) inhibitor RAPA were co-administered with G-Re in the thioacetamide (TAA)-induced rat hepatic stellate cell line (HSC-T6) to explore the mechanisms associated with G-Re...These results further support the notion that reactivation of autophagy can counteract G-Re-mediated suppression of NLRP3 and caspase-1 expression. This study highlights G-Re as a promising therapeutic candidate for liver injury, acting through inhibition of autophagy and inflammation via the PI3K/AKT/mTOR signaling pathway."

Journal • Hepatology • Liver Failure • Oncology • BECN1 • IL18 • IL1B • NLRP3 • SQSTM1 • TNFA

Hydroxychloroquine improves manifestation of PE rats under oxidative stress by regulating the PI3K/AKT/mTOR signaling pathway to inhibit autophagy. (PubMed, Sci Rep) - "Hydroxychloroquine treatment activated the PI3K/AKT/mTOR pathway and inhibited excessive autophagy to ameliorate oxidative stress injury, and these effects were attenuated after application of the PI3K inhibitor LY294002. In summary, hydroxychloroquine may inhibit autophagy by activating the PI3K/AKT/mTOR pathway, which in turn ameliorates oxidative stress injury and improves preeclampsia outcomes. Our study provides a new theoretical basis for hydroxychloroquine application for preeclampsia therapy."

Journal • Preclinical • Gynecology

Soyasapogenol B prevents sarcopenia by increasing skeletal muscle mass and function through the Sirt1/PGC-1α and PI3K pathway. (PubMed, Biomed Pharmacother) - "The upregulation of mitochondrial biogenesis and myogenic differentiation by soyasapogenol B was attenuated by treatment with EX-527, a SIRT1 inhibitor, and LY294002, a PI3K inhibitor. In conclusion, soyasapogenol B increased skeletal muscle mass, skeletal muscle strength and endurance by activating the Sirt1 and PI3K pathways. Thus, by promoting protein synthesis and mitochondrial biogenesis, soyasapogenol B could be a potential prevention option for sarcopenia."

Journal • Genetic Disorders • Obesity • Oncology • Sarcopenia

Peripheral Blood-Derived Mesenchymal Stem Cells Promote A2 Phenotype Polarization in Astrocytes via TGF-β-Mediated PI3K/Akt Pathway Activation. (PubMed, Eur J Med Res) - "This effect could also be reversed by inhibiting the PI3K/Akt pathway with LY294002 and AF-101. In conclusion, PB-MSCs can mediate the polarization of AS toward the A2 phenotype by activating the PI3K/Akt pathway."

Journal • CNS Disorders • Inflammation • Orthopedics • IL10 • IL13 • S100A10 • TGFB1

Effect of activated autophagy on an animal model of vestibular migraine-like attacks. (PubMed, Exp Neurol) - "The VMa rat model can be established by mimicking VM patients' dizziness and headache symptoms. It shows similar increased pain sensitivity, disrupted vestibular function, and autophagy dysfunction as in VM patients. Activating autophagy might provide prophylactic treatment for VM disease."

Journal • Preclinical • CNS Disorders • Migraine • Pain • FOS