LY294002 / Eli Lilly - LARVOL DELTA

Validation and analysis of key factors of Banxia Xiexin decoction against gastric cancer. (PubMed, World J Gastrointest Oncol) - "Transcriptomic and proteomic analysis showed that BXD inhibited tumor growth and slowed cancer progression by suppressing five factors in the PI3K/AKT signaling pathway, including phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, phosphoinositide-3-kinase regulatory subunit 1, and AKT serine/threonine kinase 1."

Journal • Gastric Cancer • Oncology • Solid Tumor • AKT1 • ANXA5 • HSP90AA1 • PIK3CA • PIK3R1 • TP53

Myotonic dystrophy-related CDC42-binding kinase alpha (MRCKα) mediates methionine- and leucine-stimulated β-casein synthesis in bovine mammary epithelial cells via targeting mTOR. (PubMed, Anim Nutr) - "Amino acids (AA), including methionine (Met) and leucine (Leu), stimulate milk synthesis in bovine mammary epithelial cells (BMEC) via activation of protein kinase mechanistic target of rapamycin (mTOR)...Inhibiting PI3K with LY294002 blocked Met- and Leu-induced protein expression of MRCKα and β-casein and phosphorylation of mTOR (P < 0.05). Overexpression of MRCKα increased protein levels of β-casein and phosphorylation of mTOR, which was prevented by PKB inhibitor MK2206 (P < 0.05). Our results indicate that MRCKα is a key mediator of the Met- and Leu-induced signaling cascade, acting downstream of PI3K and upstream of PKB to regulate β-casein synthesis in BMEC."

Journal • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy • CDC42

Daidzein alleviates ethanol-induced acute gastric injury in rats by targeting ESR1 and activating the PI3K/AKT/CREB signaling pathway. (PubMed, Phytomedicine) - "DAI inhibited apoptosis and preserved mucosal integrity by targeting ESR1 to activate the PI3K/AKT/CREB signaling pathway. The research elucidated the mechanisms and clinical value of DAI in the treatment of GU, offering a reference for its application as a gastric mucosal protectant in drug development and dietary supplements."

Journal • Preclinical • Gastroenterology • Gastrointestinal Disorder • Inflammation • Peptic Ulcer • EGFR • ER

Temporal changes in PTTH/Egf signaling and ERK target gene expressions during chilling in Bombyx mori eggs. (PubMed, Comp Biochem Physiol A Mol Integr Physiol) - "LY294002 (a specific phosphatidylinositol 3-kinase (PI3K) inhibitor) and U0126 (an ERK inhibitor) inhibited pointed gene expression in dechorionated eggs, indicating that both PI3K and ERK are involved in increased pointed gene expression. When eggs that had been kept at 5 °C for 30 days were transferred to 25 °C, expression levels of PTTH and pointed genes decreased after transfer, clearly indicating that continuous chilling for 45 days is necessary to sustain the higher expressions of these genes. To the best of my knowledge, this study presents the first comprehensive analysis of the transcriptional regulation of both upstream and downstream genes in the ERK signaling pathway during a chilling period, offering valuable insights into the mechanisms underlying chilling-induced diapause termination."

Journal • EGF • EGFR

Dual inhibition of AKT and autophagy sensitizes triple negative breast cancer cells to carboplatin. (PubMed, Transl Oncol) - "Current clinical treatments, primarily chemotherapy regimens based on paclitaxel and anthracycline, are associated with high recurrence rates and low overall survival rates...Further investigation demonstrated that CBP activates the AKT pathway in MDA-MB-231 cells, while its combination with LY294002 or Triciribine (inhibitors of the PI3K/AKT pathway), suppresses cell proliferation...In other words, low doses of EM-2 combined with CBP produced the same anti-tumor effects as high-dose CBP alone. These findings provide a novel strategy for the treatment of CBP using dual AKT and autophagy inhibitors, highlighting potential clinical applications."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Rosamultin attenuates cerebral ischemia/reperfusion injury by inhibiting autophagy via the PI3K/Akt/mTOR pathway. (PubMed, J Pharmacol Sci) - "However, LY294002, a PI3K inhibitor, restored the beneficial influences of Rosa after OGD/R...In addition, Rosa enhanced the p-Akt and p-mTOR levels and inhibited autophagy levels in mice after MCAO. Rosa could attenuate autophagy via activating the PI3K/Akt/mTOR axis, thereby alleviating cerebral ischemia stroke injury."

Journal • Cardiovascular • Ischemic stroke • Reperfusion Injury

Aerobic Exercise and PI3K Inhibitor Ameliorate Obesity Cardiomyopathy by Alleviating Pyroptosis in Middle-Aged Mice. (PubMed, Int J Mol Sci) - "Furthermore, the inhibition of the PI3K pathway by LY294002, coupled with exercise, attenuated and suppressed HFD-induced myocardial impairments, inflammation, and pyroptosis, with a synergistic effect. Based on these findings, we concluded that eight weeks of aerobic exercise synergizes with the inhibition of PI3K through inflammatory and pyroptosis mechanisms to improve obesity-associated myocardial remodeling and dysfunction. Therefore, long-term regular aerobic exercise represents a potential strategy in the treatment of OCM."

Journal • Preclinical • Cardiomyopathy • Cardiovascular • Genetic Disorders • Inflammation • Obesity

Matrix stiffness enhances viability, migration, invasion and invadopodia formation of oral cancer cells via PI3K/AKT pathway in vitro. (PubMed, Eur J Med Res) - "This study reveals that matrix stiffness may enhance the invasiveness and anti-apoptotic ability of OC cells by activating the PI3K/AKT pathway, which provides a new idea for exploring the microenvironmental regulation of tumor mechanics and targeted intervention strategies."

IO biomarker • Journal • Preclinical • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • BAX • BCL2 • CDH1 • CDH2

DEC1 promotes breast cancer bone metastasis through transcriptional activation of CXCR4. (PubMed, J Biomed Res) - "Notably, AMD3100 (a CXCR4 antagonist) partially reversed the DEC1-OE-induced upregulation of CXCR4 and associated pro-metastatic genes...Furthermore, pharmacological inhibition of AKT (LY294002) or JAK2 (AZD1480), but not ERK (PD98059), attenuated DEC1-mediated CXCR4 upregulation, although all three inhibitors mitigated DEC1-driven migration-related gene expression. Additionally, DEC1 enhanced CXCL12 secretion from mesenchymal stromal cells and osteoblasts, amplifying the CXCR4/CXCL12 axis within the bone microenvironment. Collectively, our findings demonstrate that DEC1 promotes breast cancer (BC) bone metastasis by directly transactivating CXCR4 expression, providing a molecular basis for targeting DEC1 to prevent and treat BC bone metastasis."

Journal • Breast Cancer • Oncology • Solid Tumor • CXCL12 • CXCR4 • JAK2

Role and mechanism of Prussian blue nanoparticles in the apoptosis of mouse adipose-derived mesenchymal stem cells treated with hydrogen peroxide (PubMed, Zhonghua Shao Shang Yu Chuang Mian Xiu Fu Za Zhi) - "Compared with those in high PBNP group, the ratios of p-PI3K/PI3K and p-Akt/Akt, as well as Bcl-2 protein expression level were significantly decreased in cells in high PBNP+LY-294002 group and high PBNP+MK-2206 group (P<0.05), while the protein expression levels of Bax, Cyt-C, cleaved caspase-9, and cleaved caspase-3 were significantly increased (P<0.05). PBNP can inhibit apoptosis of mouse ADSCs caused by oxidative stress through activating the PI3K/Akt signaling pathway and reducing the expression level of apoptosis-related proteins in cells."

IO biomarker • Journal • Preclinical • B Cell Lymphoma • Lymphoma • Oncology • BAX • CASP3 • CASP9 • CAT

Apigenin Inhibits Cell Ferroptosis by Activating the PI3K/Akt Pathway and Alleviates Renal Injury Caused by Hypertension. (PubMed, Dose Response) - "In addition, API treatment reduced the expression of glutathione peroxidase 4 (GPX4) while enhancing SLC7A11 and ACSL4 expression, which was reversed by LY294002 treatment (all, P < .001). Our experimental data suggest that API inhibits cell ferroptosis by activating the PI3K/Akt pathway and alleviates renal injury caused by hypertension."

Journal • Cardiovascular • Fibrosis • Hypertension • Immunology • Renal Disease • ACSL4 • CST3 • GPX4 • IFNG • SLC7A11 • TGFB1

Cinobufagin inhibits hepatocellular carcinoma EMT-like stemness via VEGF/VEGFR2 autocrine signaling. (PubMed, Discov Oncol) - "Cinobufagin may attenuate the PI3K/AKT-dependent metastatic potential of hepatocellular carcinoma by inhibiting the VEGFa/VEGFR2 autocrine pathway."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • Transplantation

Multidimensional Evidence Chain of Nutritional Impact on Digestive System Tumors: Integration of Mendelian Randomization Causal Inference, NHANES Epidemiological Data, and Transcriptomic Analysis. (PubMed, Nutr Cancer) - "Potentially Available Drugs: Zoledronate, LY-294002, and Everolimus may be potential choices for malnutrition digestive tract tumors. Key genes (ACTG2, MSX1, COL7A1) and gender-specific interventions offer novel strategies for precision oncology. Future validation in cross-ethnic cohorts and clinical trials is warranted."

Journal • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Metabolic Disorders • Oncology • Solid Tumor • CDH1 • COL7A1 • TP63

Changdiqing decoction (CDQD) ameliorates colitis via suppressing inflammatory macrophage activation and modulating gut microbiota. (PubMed, Phytomedicine) - "CDQD alleviates colitis by suppressing inflammatory macrophage activation and modulating the gut microbiota. Our research provides a novel traditional Chinese medicine strategy for the treatment of UC via enema administration."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Transplantation • Ulcerative Colitis • IFNG

Apigenin attenuates the atherosclerotic lesions through enhancing selective autophagy/lipophagy and promoting RCT process. (PubMed, Pharm Biol) - "Then triton WR-1339 (TWR) was injected into muscles of C57BL/6 mice, and the role of autophagy was assessed by autophagy inhibitor LY294002 intervention...The TEM and IFM images revealed that apigenin promoted the formation of autophagosomes and the co-localization between autophagy proteins with lipid protein. The lipid-lowering effects of apigenin were mediated through promoting RCT and enhancing selective lipophagy, meanwhile it provided a potential therapeutic option for atherosclerosis."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Metabolic Disorders • APOE

Mechanisms of aerobic exercise on doxorubicin-induced cardiomyocyte apoptosis: based on AMPK/PI3K/AKT signalling pathway. (PubMed, Life Sci) - "Our findings indicate aerobic exercise may protect against myocardial damage by activating the AMPK/PI3K/AKT signalling pathway, offering insights into the molecular mechanisms of cardioprotection and highlighting the potential benefits of exercise."

Journal • Cardiovascular • Fibrosis • Immunology • Oncology

TRPV4-dependent signaling pathways play essential regulatory roles in high salt-induced cardiac hypertrophy via autophagic alterations. (PubMed, J Cardiovasc Pharmacol) - "Salt-induced autophagic activity was enhanced by inhibiting Class I PI3-Kinase (PI3KC1) with LY294002 or Akt with AZD5363, but got undermined by AMPK inhibition with Compound C (CC) or SIRT1 inhibition with EX-527...Thus, both PI3KC1 and AMPK signaling pathways participate in salt-induced cardiac hypertrophy via shared upstream component of TRPV4: lower salt triggers AMPK, scavenges ROS, preventing cardiac hypertrophy, whilst higher salt activates PI3KC1 with opposite effects. Our findings illuminate potential therapeutic effects of interfering TRP-related channels on high salt-induced hypertrophy and other mechanical stretch force-associated diseases."

Journal • Cardiovascular • Congestive Heart Failure • Fibrosis • Gene Therapies • Heart Failure • Hypertension • Immunology • TRPV4

Anti-Inflammatory Mechanisms of Pleurotus citrinopileatus: Inhibition of MAPK and NF-κB Signaling Pathways, and Activation of ROS/PI3K/Nrf2/HO-1 Signaling Pathway in LPS-Stimulated RAW264.7 Cells. (PubMed, J Microbiol Biotechnol) - "Furthermore, treatment with the HE, DCM, and EA fractions enhanced phosphoinositide 3-kinase (PI3K) activation, whereas PI3K inhibition by LY294002 attenuated HO-1 expression and nuclear Nrf2 translocation. Reactive oxygen species (ROS) scavenging by N-acetyl-L-cysteine (NAC) similarly reduced PI3K activation and the upregulation of HO-1 and nuclear Nrf2. Collectively, these findings indicate that the HE, DCM, and EA fractions mitigate NO production by downregulating iNOS expression through the suppression of MAPK and NF-κB signaling, while also engaging the ROS/PI3K/Nrf2/HO-1 pathway to exert anti-inflammatory effects."

Journal • Inflammation • HMOX1 • MAPK8 • NFE2L2

REALGAR-INDIGO NATURALIS FORMULA EXERTS AN ANTI-TUMOR EFFECT IN TUMOR-BEARING NUDE MICE BY ENHANCING THE AUTOPHAGY LEVEL TO PROMOTE THE APOPTOSIS OF ARSENIC-RESISTANT TUMOR CELLS. (EHA 2025) - "Background: In China, the Chinese patent drug Realgar-Indigo naturalis Formula (RIF) has been used as an alternative therapy to intravenous arsenic trioxide for treating acute promyelocytic leukemia (APL).Comprising four traditional Chinese herbs-Realgar, Indigo naturalis, Salvia miltiorrhiza, and Pseudostellaria heterophylla-RIF notably contains tetra-arsenic tetra-sulfide, indirubin, tanshinone IIa, and total saponins of Radix Pseudostellariae as its primary active components...In vitro, the killing effect of arsenic disulfide on cells under different autophagy states was studied using the autophagy pathway intervention agents LY294002 (PI3K inhibitor) and Baf A1 (autophagosome degradation inhibitor)... The synergistic effect of the component combination of RIF can regulate autophagy through the PI3K/Akt/mTOR pathway, enhance tumor cell apoptosis, inhibit tumor growth, and treat arsenic-resistant APL."

Preclinical • Tumor cell • Acute Promyelocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • RARA

Ergothioneine Suppresses Amyloid Β-Induced Tau Phosphorylation and Cytotoxicity by Inactivating Glycogen Synthase Kinase-3β in Cultured Neurons. (PubMed, Curr Mol Pharmacol) - "ERGO may suppress the increased expression of p-Tau and proteins involved in Aβ production induced by Aβ oligomers by inactivating GSK-3β, thereby mitigating neurotoxicity."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • BACE1 • CHAT • GSK3B

STOML2 inhibits sorafenib-induced ferroptosis in hepatocellular carcinoma via p-AKT signaling pathway. (PubMed, Am J Cancer Res) - "The AKT inhibitor LY294002 exhibited synergistic antitumor effects with sorafenib in HCC. In conclusion, the present study demonstrated that STOML2 could enhance the AKT-SLC7A11-mediated antioxidant capacity in HCC, inhibit ferroptosis and reduce the sensitivity of HCC to sorafenib, providing a theoretical basis for the combination of LY294002 and sorafenib."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • SLC7A11 • STOML2

Study on the effect and mechanism of PM2.5 on the expression of alzheimer's-like lesions related proteins in SH-SY5Y cells. (PubMed, Toxicol Lett) - "Based on bioinformatics results, the study employed a PI3K inhibitor (LY294002, 10 μmol/L for 1h) and a reactive oxygen species (ROS) inhibitor, N-acetyl-L-cysteine (NAC, 5 nmol/L for 1h), as interventions...Furthermore, the ROS/PI3K/Akt/GSK-3β pathway was found to play a key role in these processes. This research provides a basis for understanding the impact of PM2.5 on Alzheimer's disease patients and offers recommendations for the prevention of haze-related health risks, as well as for risk management by relevant governmental departments."

Journal • Alzheimer's Disease • CNS Disorders

Quercetin Induces Apoptosis Through Downregulating P4HA2 and Inhibiting the PI3K/Akt/mTOR Axis in Hepatocellular Carcinoma Cells: An In Vitro Study. (PubMed, Cancer Rep (Hoboken)) - "This investigation reveals that quercetin compels apoptosis in HCC cells by diminishing P4HA2 and restraining the PI3K/Akt/mTOR axis."

Journal • Preclinical • Hepatocellular Cancer • Oncology • Solid Tumor • P4HA2

Effects and mechanisms of trifolin on attenuating hypertension-induced vascular smooth muscle cell proliferation and collagen deposition in vivo and in vitro. (PubMed, Sci Rep) - "Mice were randomly allocated into six groups: control, Ang II, Ang II + Trifolin (0.1 mg/kg), Ang II + Trifolin (1 mg/kg), Ang II + Trifolin (10 mg/kg), and Ang II + Valsartan (10 mg/kg)...In vitro study indicated that trifolin consistently reduced the cell viability, down-regulated the expression of PCNA, collagen I and collagen III, and reduced the cell migration, as well as reduced the ratio of p-PI3K/PI3K and p-AKT/AKT (similar with the effect of PI3K inhibitor: LY294002) in Ang II stimulated A7R5 cells. Trifolin treatment attenuated the elevation of blood pressure, the proliferation and collagen deposition of VSMCs, and modulated multiple signaling pathways, including PI3K/Akt pathway. These results suggest that trifolin could be a potential therapeutic approach for treating hypertension."

Journal • Preclinical • Cardiovascular • Hypertension • Oncology • PCNA

Muscone Attenuates Uveitis Through the PI3K/AKT Signaling Pathway. (PubMed, Invest Ophthalmol Vis Sci) - "Moreover, by using LY294002 to specifically inhibit PI3K, we observed a marked decrease in inflammatory phenotype and BRB destruction of EAU. In summary, this study establishes the protective efficacy of Muscone against the progression of EAU and provides insights into the molecular mechanisms responsible for its therapeutic action."

Journal • Immunology • Inflammation • Ocular Inflammation • Ophthalmology • Uveitis • IFNG