LY294002 / Eli Lilly - LARVOL DELTA

Akt/SIRT3-dependent mitochondrial autophagy inhibits apoptosis of alveolar epithelial cells and alleviates hyperoxia-induced acute lung injury (PubMed, Zhonghua Wei Zhong Bing Ji Jiu Yi Xue) - "Activation of the Akt/SIRT3 signaling pathway promotes mitophagy to inhibit alveolar epithelial cell apoptosis, thereby attenuating HALI."

IO biomarker • Journal • Acute Lung Injury • Respiratory Diseases • BAX • BCL2 • BECN1 • CASP3 • GAPDH • SIRT3

H3K18 lactylation promotes POM121 transcription and accelerates gastric cancer progression via the PI3K/AKT pathway. (PubMed, Pathol Res Pract) - "H3K18la enhances the malignant behavior of GC cells through activation of the POM121/PI3K/AKT pathway. These findings provide new insights into the role of histone lactylation in GC progression and suggest that targeting the H3K18la-POM121-PI3K/AKT axis may represent a potential therapeutic avenue worthy of further investigation."

Journal • Gastric Cancer • Oncology • Solid Tumor • LDHA • LDHB • POM121

Venlafaxine upregulates cortical catechol-O-methyltransferase expression and activity in rats and mice. (PubMed, Drug Metab Dispos) - "Phosphatidylinositol 3-kinase inhibitor LY294002, mammalian target of rapamycin inhibitor rapamycin, silencing P70S6K, or silencing 4EBP1 remarkably attenuated venlafaxine-induced upregulation of COMT...Furthermore, COMT inhibitor tolcapone reversed venlafaxine-induced decreases in SAM levels, H3K4me3 and H3K27me3 expression, and locomotor and exploration activities...SIGNIFICANCE STATEMENT: This study revealed that venlafaxine upregulated cortical catechol-O-methyltransferase expression and activity via activating phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway. The induction of catechol-O-methyltransferase led to depletion of cortical S-adenosylmethionine, which may partly contribute to the decreases in locomotor and exploration activities and downregulations of H3K4me3 and H3K27me3 expression in cortex of rats and mice."

Journal • Preclinical • COMT • EIF4EBP1

LY294002 and LiCl Mitigate Neonatal ExPEC Meningitis Through Akt/GSK3β Signaling Modulation. (PubMed, Mediators Inflamm) - "LY294002 and LiCl reduced neuroinflammation and preserved the blood-brain barrier (BBB) integrity in the neonatal ExPEC meningitis model, likely via modulation of the Akt/GSK3β pathway. These results underscore the potential of this pathway as a therapeutic target and provide a basis for further preclinical investigation."

Journal • CNS Disorders • Infectious Disease • Inflammation • GSK3B

Decoding the DKK1/CKAP4 signaling Axis: A novel mechanism driving Neointimal hyperplasia in arteriovenous fistulas. (PubMed, Int Immunopharmacol) - "The upregulation of DKK1 drives VSMC migration and proliferation via CKAP4-mediated PI3K/Akt activation, thereby exacerbating NIH and ultimately leading to the failure of AVFs."

Journal • Cardiovascular • Chronic Kidney Disease • Nephrology • Renal Disease • CKAP4 • DKK1 • VIM

The MYBL2-GTSE1 axis promotes laryngeal squamous cell carcinoma progression by regulating PI3K/AKT-dependent glycolytic reprogramming. (PubMed, Cancer Biol Ther) - "Importantly, these oncogenic effects were effectively reversed by GTSE1 knockdown or PI3K inhibition with LY294002, validating the pathway's functional significance. The MYBL2-GTSE1 axis promotes LSCC progression through PI3K/AKT-mediated metabolic reprogramming, representing a promising therapeutic target."

Journal • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • GTSE1 • LDHA • MYBL2 • PKM • SLC2A1

TRANSFORMING GROWTH FACTOR-Β1 ACTS VIA TΒR-I ON MICROGLIA TO PROTECT AGAINST MPP+-INDUCED DOPAMINERGIC NEURONAL LOSS (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

Quercetin attenuates deoxynivalenol-induced muscle developmental disorders in broilers by modulating the PI3K/Akt/mTOR pathway and reducing apoptosis. (PubMed, Poult Sci) - "For in vitro experiments, myoblasts were used as experimental subjects to establish intervention models with LY294002, Z-VAD-FMK, and IBS008738...Moreover, inhibition of apoptosis, but not promotion of myogenesis, directly alleviated DON-induced muscle defects, establishing apoptosis as the causative event. In conclusion, our data demonstrated that QUE alleviated DON-induced apoptosis via the PI3K/Akt/mTOR pathway, thereby mitigating muscle development disorders."

Journal • CNS Disorders • Developmental Disorders • Psychiatry

Paeonol alleviates granulosa cell senescence in laying chickens via the PI3K/Akt/mTOR signaling pathway. (PubMed, Poult Sci) - "These findings indicate that Paeonol may mitigate D-gal-associated GC senescence and mitochondrial impairment, with PI3K/Akt /mTOR signaling potentially contributing to these effects. Paeonol warrants further evaluation as a dietary supplement for supporting reproductive function in late-laying hens."

Journal • Metabolic Disorders

Investigating the Mechanism of Rehmannia glutinosa-Ephedra sinica in heart failure with preserved ejection fraction by Network Pharmacology, Metabolomics and Experimental Validation. (PubMed, J Ethnopharmacol) - "MD exerts cardioprotective effects in HFpEF by modulating metabolic dysfunction and ferroptosis, which may be associated with the activation of the PI3K/AKT and GPX4/ACSL4 pathways."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Metabolic Disorders • ACSL4 • GPX4

Remimazolam alleviates blood-brain barrier damage by regulating the PI3K/AKT signaling pathway in sepsis-associated encephalopathy mice. (PubMed, Brain Res Bull) - "Notably, co-administration of LY294002 abolished the protective effects of remimazolam, indicating a critical role for PI3K/AKT signaling in mediating its neuroprotective actions. These findings suggest that remimazolam may represent a promising therapeutic candidate for targeting the pathogenesis of SAE."

Journal • Preclinical • CNS Disorders • Infectious Disease • Inflammation • Septic Shock • IL1B • IL6 • OCLN • TJP1

Role and Mechanism of BRIP1 in Anoikis Resistance of Gastric Cancer. (PubMed, Int J Mol Sci) - "We found that the PI3K inhibitor LY294002 counteracted BRIP1-driven oncogenic effects, which was evidenced by restored expression of key regulators governing apoptosis, cell cycle progression, and EMT, in addition to suppressed proliferation in GC cells. BRIP1 is postulated to function upstream of the PI3K/Akt signaling cascade. This study establishes a risk scoring model and identifies BRIP1 as a potential prognostic marker for GC."

Journal • Gastric Cancer • Oncology • Solid Tumor • BRIP1 • DUSP1 • TXNIP

IKZF3 Promotes Gastric cancer Progression and Oxaliplatin Resistance via PI3K/AKT/mTOR Activation. (PubMed, J Gastroenterol Hepatol) - "IKZF3 drives GC progression and oxaliplatin resistance by activating PI3K/AKT/mTOR signaling. It is a potential prognostic biomarker and therapeutic target, supporting further development of LY294002 and Iberdomide for GC treatment."

Journal • Gastric Cancer • Oncology • Solid Tumor • IKZF3

Nodakenin attenuates cerebral ischemia-reperfusion injury by modulating the PI3K/AKT/NF-κB signaling pathway. (PubMed, Immunopharmacol Immunotoxicol) - "These protective effects were abolished by PI3K inhibitor LY294002. Nodakenin exerted neuroprotective effects against cerebral I/R injury by regulating the PI3K/AKT/NF-κB pathway to reduce neuroinflammation, oxidative stress and ferroptosis. These findings identify Nodakenin as a promising candidate for limiting secondary injury after ischemic stroke."

Journal • Cardiovascular • CNS Disorders • Inflammation • Ischemic stroke • Oncology • Reperfusion Injury • GPX4 • IL1B • IL6 • TNFA

Berberine Ameliorates Pulmonary Fibrosis via Downregulating the TGFBR2-Mediated Signaling. (PubMed, Chem Biol Drug Des) - "In vivo, BBR was administered by gavage following intratracheal instillation of bleomycin (BLM) in a mouse model from Day 1 to Day 20...Both cell lines were transfected with a lentivirus carrying TGF-β receptor 2 (TGFBR2) knockdown genes, and the autophagy inhibitor chloroquine (CQ) and PI3K inhibitor LY294002 were employed to investigate the underlying effects of BBR on TGF-β signaling and autophagy in pulmonary fibrosis...The effect of BBR on pulmonary fibrosis was further verified using both TGF-β1-treated HLF and A549 cells with the addition of the inhibitors of PI3K, LY294002, and autophagy, CQ in vitro, respectively. Our study suggests that BBR can inhibit pulmonary fibrosis by down-regulating the expression of TGFBR2, attenuating TGF-β/Smad2/3 signal, and activating autophagy through phosphorylation of PI3K/AKT/mTOR."

Journal • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Interstitial Lung Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • TGFB1 • TGFBR2

Qiangjing Tablets modulate oxidative stress and endoplasmic reticulum stress through the PI3K/Akt/NRF-2 signaling axis and regulate gut microbiota in ornidazole-induced asthenozoospermia rats. (PubMed, J Tradit Complement Med) - "QJT and LY294002 (PI3K inhibitor) were supplied to the ORN-induced rats...QJT modulated oxidative stress and ER stress via the PI3K/Akt/NRF-2 signaling axis and maintained gut microbiota homeostasis in AZS rats. This study will lay a theoretical basis for the treatment of AZS and male fertility."

Journal • Preclinical • Infertility • Metabolic Disorders • Sexual Disorders • ATF6 • PERK

Methylophiopogonanone a attenuates pulmonary fibrosis by inhibiting SPP1-mediated macrophage polarization via the PI3K/Akt pathway. (PubMed, Animal Model Exp Med) - "This study identifies that MOA is a promising natural compound that alleviates pulmonary fibrosis by inhibiting SPP1-mediated macrophage polarization via the PI3K/Akt pathway."

Journal • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • IL4 • SPP1

Mechanisms of Anti-Oxidants, N-Acetylcysteine and Elamipretide (SS-31), on Ozone-Induced Airway Hyperresponsiveness and Mucus Hypersecretion. (PubMed, Lung) - "NAC and SS-31 protect against acute O₃-induced AHR and AMH by alleviating oxidative stress and suppressing PI3K/AKT-driven inflammatory and pyroptotic pathways. Targeting oxidative stress, including mitochondrial ROS, may represent a viable strategy to mitigate airway damage caused by acute O₃ exposure."

Journal • Inflammation • Respiratory Diseases • MUC5B • NLRP3

Mechanistic Insights into the Antidepressant Effects of the Angelica sinensis and Ligusticum chuanxiong Herb Pair: Involvement of the PI3K/AKT Signaling Pathway. (PubMed, J Ethnopharmacol) - "DC exhibits potent antidepressant effects by modulating the PI3K/AKT pathway to enhance neurotransmitter release and reduce inflammatory factor levels. This mechanism protects neurons and alleviates neuroinflammation, thereby exerting antidepressant effects."

Journal • CNS Disorders • Depression • Inflammation • Psychiatry • IL1B • IL6 • TNFA

Ursolic Acid Attenuates Bone Loss by Stabilizing Osteoblast Mitochondrial Integrity and Inhibiting Downstream Apoptosis via PI3K-AKT-Bcl2 Signaling. (PubMed, Eur J Pharmacol) - "UA promotes osteoblast differentiation and mitigates mitochondrial dysfunction by activating PI3K-AKT-Bcl2 signaling. The findings provide evidence supporting UA as a potential therapeutic candidate for OP."

IO biomarker • Journal • Metabolic Disorders • Osteoporosis • Rheumatology • BCL2

Simo Tang mitigates mitochondria-dependent apoptosis via PI3K/AKT pathway activation in Chronic atrophic gastritis. (PubMed, J Ethnopharmacol) - "By orchestrating the PI3K/AKT cascade, SMT simultaneously elevates antioxidant enzyme activity, maintains mitochondrial homeostasis, suppresses pro-apoptotic and pro-inflammatory signalling, thereby attenuating gastric mucosal injury and retarding CAG progression."

IO biomarker • Journal • Dyspepsia • Gastrointestinal Disorder • Inflammation • APAF1 • BCL2 • CASP9 • CCND1 • IL6 • TNFA

Fisetin Targets Multiple Signaling Pathways to Suppress Microglia-Mediated Neuroinflammation and Cognitive Decline in Alzheimer's Disease. (PubMed, Neuropharmacology) - "Furthermore, conditioned medium from fisetin-treated microglia alleviated neuronal damage and restored the expression of BDNF and PSD95 in primary neurons. The collective findings, along with experimental studies utilizing the PI3K inhibitor (LY294002), indicate that PI3K may act as a molecular target of fisetin, underscoring its potential therapeutic significance in regulating early inflammatory processes in AD."

Journal • Alzheimer's Disease • CNS Disorders • Inflammation • DLG4

Sulforaphane Attenuates Methamphetamine-Induced Neurotoxicity via Activation of the PI3K/AKT Pathway. (PubMed, J Biochem Mol Toxicol) - "These protective effects were associated with increased phosphorylation of PI3K and AKT, and were markedly diminished by the PI3K inhibitor LY294002. In a METH-induced neurotoxicity mouse model, SFN ameliorated hippocampal histopathological damage, reduced TUNEL-positive apoptotic cells, and normalized the expression of BAX, Bcl-2, cleaved caspase-3, and phosphorylated PI3K/AKT. These findings suggest that SFN alleviates METH-induced neurotoxicity by activating the PI3K/AKT pathway and inhibiting mitochondria-dependent apoptosis, providing evidence for its potential as a therapeutic candidate for METH-related neuronal injury."

IO biomarker • Journal • BAX • BCL2 • CASP3

RHBDD1 promotes cervical cancer progression by activating the EGFR/PI3K/AKT signaling pathway. (PubMed, Arch Biochem Biophys) - "RHBDD1 facilitates CC progression by promoting proliferation, EMT, migration, invasion, and tumorigenesis through activation of the EGFR/PI3K/AKT pathway, likely via direct receptor-level interaction. Targeting this regulatory node may offer a promising therapeutic approach for CC."

Journal • Cervical Cancer • Oncology • Solid Tumor • RHBDD1 • SNAI1

MEK1/2 Inhibitor (U0126) and PI3K Inhibitor (LY294002) Suppress Herpes Simplex Virus Type 1 Replication by Targeting MAPK/ERK1/2 and PI3K/AKT Signaling Pathways: Implications for Oral Health and Translational Control of Orolabial HSV-1 Infection. (PubMed, Iran J Pharm Res) - "These findings position MEK1/2 and PI3K as promising therapeutic nodes for managing cutaneous HSV-1 infections. This host-directed dual-pathway inhibition may therefore help reduce recurrent orolabial HSV-1 lesions."

Journal • Herpes Simplex • Infectious Disease • Inflammation • Oncology • IL6 • MAPK1 • TNFA