LY294002 / Eli Lilly - LARVOL DELTA

PPARGC1A as an Epigenetic Biomarker of Differentiation in Differentiated Thyroid Cancer (ETA 2026) - "Similarly, thyroid cancer redifferentiation models, including treatments with LY294002 (PI3K inhibitor), PD325901 (ERK/MAPK inhibitor), Trichostatin A (histone deacetylase inhibitor) and 5-azacytidine (DNA methyltransferase inhibitor), also resulted in an increased PPARGC1A expression alongside the TDS, reinforcing the link between PPARGC1A and differentiation state. In conclusion, we have identified PPARGC1A as an epigenetic factor with a great potential as a biomarker of differentiation in DTC. Understanding its role may provide new insights into tumour dedifferentiation and open new avenues for therapeutic strategies in advanced thyroid carcinomas."

Biomarker • Oncology • Solid Tumor • Thyroid Gland Carcinoma • PPARGC1A

Targeting V-Domain Ig Suppressor of T Cell Activation (VISTA) in Malignant Mesothelioma (IASLC-WCLC 2026) - "To understand and modulate key signaling pathways involved in VISTA expression, we conducted experiments treating cells with Trametinib, LY294002, capivasertib, and ruxolitinib. The IncuCyte analysis showed that both VISTA- and Mesothelin-targeted CAR T-cells at the lower E:T ratios of 0.5:1 and 1:1 led to potent killing of the MM cell lines HAY, H2461, and H2373. Conclusions : These findings offer valuable insights into the regulatory mechanisms governing VISTA-mediated immunoregulation in MM, as well as the effectiveness of VISTA- and mesothelin-targeted CAR T-cells in malignant mesothelioma."

IO biomarker • Mesothelioma • Solid Tumor • MSLN • VSIR

The regulatory effect of PI3K/Akt/HIF-1α glycolytic signaling pathway on the metabolites in urine of mice with bleomycin-induced pulmonary fibrosis model (PubMed, Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi) - " From May to October 2023, 36 C57BL/6 mice were randomly divided into six groups (n=6 each): control (BD) group, bleomycin model (BM) group, early PI3K inhibitor (LY294002) intervention (BZLY) group, late PI3K inhibitor intervention (BWLY) group, early HIF-1α inhibitor[2-methoxyestradiol(2-ME2) ] intervention (BZ2M) group, and late HIF-1α inhibitor intervention (BW2M) group. Pathway enrichment analysis revealed 6 significantly altered metabolic pathways: purine metabolism, linoleic acid metabolism, α-linolenic acid metabolism, riboflavin metabolism, sphingolipid metabolism, and tyrosine metabolism (P<0.05) . The PI3K/Akt/HIF-1α glycolytic signaling pathway may regulate the development and progression of idiopathic pulmonary fibrosis through purine metabolism, linoleic acid metabolism, α-linolenic acid metabolism, riboflavin metabolism, sphingolipid metabolism, and tyrosine metabolism pathways."

Journal • Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Metabolic Disorders • Pulmonary Disease • Respiratory Diseases • HIF1A

Trimethylamine N-oxide, a Gut Microbiota Metabolite, Promotes Diabetes-Mediated Erectile Dysfunction via a PANoptotic-Like Process Involving Pyroptosis, Apoptosis, and Necroptosis in CCSMCs. (PubMed, Andrology) - "Gut microbiota dysbiosis in T1DMED rats was associated with elevated serum TMAO, and TMAO triggered a PANoptotic-like process in CCSMCs via PI3K/Akt activation, thereby contributing to the progression of DMED."

Journal • Diabetes • Erectile Dysfunction • Gastrointestinal Disorder • Metabolic Disorders • Type 1 Diabetes Mellitus • CASP3 • CASP8 • NOS3

FSCN1 Modulates Fatty Acid Metabolism and the Coordinated Activation of AKT/mTOR and p38 MAPK Pathways in Colorectal Cancer Cells. (PubMed, Oncol Res) - "Mechanistically, FSCN1 was associated with activation of the protein kinase B/mammalian target of rapamycin (AKT/mTOR) and p38 mitogen-activated protein kinase (p38 MAPK) pathways; pharmacological inhibition with LY294002 or SB203580 phenocopied the lipid-lowering effects of FSCN1 knockdown. Collectively, these findings link FSCN1 to the AKT/mTOR/SREBP1/(FASN/SCD1) lipogenic axis and the p38 MAPK/PPARα/ACOX1 peroxisomal FAO pathway, implicating FSCN1 in lipid metabolic regulation and CRC progression, while suggesting a putative functional regulatory axis and a promising candidate therapeutic target for CRC."

Journal • Colorectal Cancer • Oncology • Solid Tumor • ACOX1 • Fascin • FASN • FSCN1 • mTOR • PPARA • SCD

POFUT1 Serves as an Independent Prognostic Factor and Therapeutic Target by Activating the PI3K/AKT Pathway in Glioma. (PubMed, Brain Behav) - "POFUT1 as a key driver of glioma malignancy, predominantly through activating the PI3K-AKT signaling pathway. These findings highlight POFUT1 as a promising novel therapeutic target for aggressive glioma."

Biomarker • Journal • Brain Cancer • Glioma • Oncology • Solid Tumor

Jaceidin Inhibits Proliferation and Promotes Apoptosis in Oral Squamous Cell Carcinoma Cells by Regulating Survivin and AKT/ERK Signaling Pathways. (PubMed, Int J Mol Sci) - "In addition, JAC attenuated AKT and ERK1/2 phosphorylation, and pharmacological inhibition with LY294002 or U0126 further enhanced JAC-induced apoptotic signaling. Furthermore, JAC reduced survivin expression and attenuated survivin-mediated apoptotic resistance. These findings suggest that JAC suppresses OSCC cell survival in association with modulation of AKT/ERK-survivin signaling and caspase-dependent apoptosis."

Journal • Oncology • Oral Cancer • Squamous Cell Carcinoma • BAX • BCL2L11 • BIRC5 • CASP3 • CASP8 • CASP9 • CCND1 • CCNE1 • CDK1 • CDK2 • PARP1 • TNFRSF10B • TRADD

Salvianolic Acid B Inhibits Ferroptosis in Acute Lung Injury: Network Analysis and Experimental Validation. (PubMed, J Cell Mol Med) - "In vitro and in vivo evidence confirmed that Sal B attenuates LPS-induced ALI by inhibiting ferroptosis via the PI3K/AKT axis, as corroborated by LY294002 and si-ALB intervention. RNA sequencing and network pharmacological analysis synergistically revealed the PI3K/AKT pathway as a potential signalling pathway for Sal B. Sal B ameliorates sepsis-induced ALI via a defined mechanism that involves the activation of the PI3K-AKT pathway, thereby inhibiting ferroptosis both in vivo and in vitro."

Journal • Acute Lung Injury • Infectious Disease • Respiratory Diseases • Septic Shock • IL17A

Bupleuri Radix- Aurantii Fructus Immaturus pair attenuates metabolic dysfunction-associated fatty liver disease in association with modulation of PI3K/Akt-GSK3β/FoxO1 pathway: Evidence from multi-model validation including human iPSC-derived liver organoids. (PubMed, J Ethnopharmacol) - "With BAP as the research subject, this study conducts cross-validation across a multi-model system including whole-animal models, hepatocytes and human liver organoids, and suggests that BAP ameliorates glucolipid metabolic disorders and slows MAFLD progression, effects that are closely associated with modulation of the PI3K/Akt-GSK3β/FoxO1 signaling pathway. These findings provide novel compatibility insights and experimental evidence for traditional Chinese medicine-based intervention of MAFLD."

Journal • CNS Disorders • Depression • Hepatology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Psychiatry • CPT1A • FASN • PPARA

N-acetylcysteine restores osteogenesis in human periodontal ligament stem cells by attenuating HIF-1α-driven oxidative stress and glycolytic reprogramming. (PubMed, J Dent Sci) - "Cells were treated with the antioxidant N-acetylcysteine (NAC), the glycolysis inhibitor 2-deoxy-d-glucose (2-DG), or the PI3K inhibitor LY294002. HIF-1α stabilization suppresses hPDLSC osteogenesis by inducing both oxidative stress and pathological glycolytic reprogramming. Targeted antioxidant intervention effectively mitigates these impairments, highlighting the ROS/PI3K/Akt/HIF-1α axis as a key link between redox imbalance and metabolic dysfunction, and suggesting a potential therapeutic target for periodontal regeneration."

Journal • Dental Disorders • Metabolic Disorders • Periodontitis • HIF1A • RUNX2 • SLC2A1

Lysicamine: a Potential Redifferentiation Agent for Thyroid Cancer Cells Identified via a Non-radioactive Iodide Uptake Screening (ETA 2026) - "Pd184352 and Ly294002, ERK and PI3K inhibitors respectively, were used as positive controls. Lysicamine promoted iodide uptake and upregulated key thyroid differentiation markers in both non-tumoral and anaplastic thyroid cancer cells, highlighting its potential as a novel redifferentiation agent. Since lysicamine inhibits the PI3K/AKT pathway, as previously demonstrated by our group, this mechanism may contribute to the enhancement of NIS expression and function. Thus, lysicamine may represent a promising strategy to restore radioiodine responsiveness in aggressive thyroid tumors."

Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • PAX8

Low-dose N-methyl-D-aspartate protects against amyloid-β-induced neurotoxicity by suppressing the MLK3-MKK7-JNK3 pathway and activating the PI3K-PDK1-Akt pathway. (PubMed, Neuroreport) - "Low-dose NMDA exerts neuroprotective effects against Aβ-induced neurotoxicity. These effects are mediated by the dual modulation of the pro-survival PI3K-PDK1-Akt pathway and the pro-apoptotic MLK3-MKK7-JNK3 pathway."

Journal • Alzheimer's Disease • CNS Disorders • MAP3K11

Dual modulation of lipid-lowering and anti-inflammatory effects of Thymus quinquecostatus Celak. ethanol extract on atherosclerosis: integration of UPLC-Q-TOF-MS/MS, in silico, in vivo, and in vitro studies. (PubMed, J Sci Food Agric) - "This study shows the potential of TEE as a functional food for lipid-lowering and anti-inflammatory strategies in cases of AS."

Journal • Atherosclerosis • Cardiovascular • Inflammation • IL6 • mTOR • PIK3R1

Terazosin Alleviates Apoptosis and Neuroinflammation in Cerebral Ischemia-reperfusion Injury via Activating the PI3K/AKT/mTOR Signaling Pathway. (PubMed, Curr Neuropharmacol) - "In summary, this study demonstrates that TZ exerts neuroprotective effects against CIRI by activating the PI3K/AKT/mTOR signaling pathway. These results provide a preclinical basis for repurposing TZ as a treatment for ischemic stroke and highlight the PI3K/AKT/mTOR axis as a potential neuroprotective target."

IO biomarker • Journal • Cardiovascular • CNS Disorders • Inflammation • Ischemic stroke • Reperfusion Injury • BAX • BCL2 • IL1B • IL6 • PIK3CA • TNFA

Dopamine receptor D1 is altered in atrial fibrillation-associated tissues and modulates Ang II-induced cardiomyocyte stress partly through PI3K/Akt signaling. (PubMed, Mol Biol Rep) - "DRD1 expression is altered in EAT and downregulated in the myocardial tissue of patients with AF and in experimental atrial remodeling. DRD1 overexpression protects cardiomyocytes against Ang II-induced stress, with PI3K/Akt signaling contributing to this effect. However, whether DRD1 causally regulates AF susceptibility in vivo remains to be established."

Journal • Atrial Fibrillation • Cardiovascular • Inflammation • AKT1 • DRD1 • NLRP3

ZDWX-25, a dual DYRK1A/GSK3β inhibitor, attenuates tau hyperphosphorylation and neuroinflammation in acute mouse models. (PubMed, Front Pharmacol) - "The PI3K inhibitor LY294002 was used in HT22 and BV2 cells...ZDWX-25 attenuates tau pathology via dual direct/indirect mechanisms and enhances microglial clearance; it also shows preliminary anti-neuroinflammatory effects. These findings support ZDWX-25 as a multi-target candidate for Alzheimer's disease."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Inflammation • DLG4 • IL6 • TNFA

Artemisinin alleviates hippocampal neuronal apoptosis and cognitive impairment in rats after cardiac arrest resuscitation: Association with the PI3K/Akt pathway. (PubMed, Pak J Pharm Sci) - "Artemisinin alleviates hippocampal neuronal apoptosis and improves neurological deficits and cognitive dysfunction in rats after cardiac arrest resuscitation, suggesting a possible association with activation of the phosphatidylinositol 3-kinase/protein kinase B pathway. Limitations include use of a single pharmacological inhibitor and lack of genetic validation."

Journal • Preclinical • Alzheimer's Disease • Cardiovascular • CNS Disorders • Cognitive Disorders • Vascular Neurology

Mogrol Protects Against Warm Hepatic Ischemia-Reperfusion Injury by Preserving Mitochondrial Function through PI3K/AKT/GSK3β Signaling. (PubMed, Eur J Pharmacol) - "Mogrol mitigates warm HIRI, at least in part, by activating the PI3K/AKT/GSK3β signaling pathway, thus highlighting its potential as a naturally derived candidate for liver protection."

Journal • Cardiovascular • Inflammation • Metabolic Disorders • Reperfusion Injury • GSK3B

Epimedii Folium-Ligustri Lucidi Fructus protects airway epithelial barrier from recurrent injury by inhibiting PI3K (PubMed, Zhongguo Zhong Yao Za Zhi) - "PI3K inhibitor(LY294002), YN-containing serum, PI3K agonist(740 Y-P), or YN-containing serum+740 Y-P were administered in corresponding groups...Notably, the protective effects of YN were partially reversed by the PI3K agonist. These findings indicate that YN mitigates recurrent airway epithelial injury and restores barrier function primarily through inhibiting the PI3K pathway."

Journal • Asthma • Pulmonary Disease • Respiratory Diseases • CDH1 • CTNNB1 • OCLN • TJP1 • VIM

MiR-326 targets ETS1 to activate PI3K/Akt signaling and promote malignant phenotypes in gastric cancer cells. (PubMed, Pak J Pharm Sci) - "miR-326 promotes malignant phenotypes in gastric cancer cells by targeting ETS1, activating the PI3K/Akt signaling pathway, and inducing dysregulation of inflammatory cytokines. The miR-326/ETS1/PI3K/Akt axis may serve as a potential diagnostic biomarker and therapeutic target for gastric cancer."

Journal • Gastric Cancer • Oncology • Solid Tumor • ETS1 • IL10 • IL17A • IL6 • MIR326 • TNFA

Protein 4.1 R Suppresses Melanoma Progression by Inhibiting Glycolysis via the PI3K/AKT/mTOR Pathway. (PubMed, Mol Carcinog) - "Treatment with the PI3K inhibitor LY294002 partially reversed the effects of protein 4.1 R knockdown on melanoma cells. In conclusion, these findings suggest that protein 4.1 R may negatively regulate melanoma progression through mechanisms associated with glycolytic remodeling and PI3K/AKT/mTOR signaling."

Journal • Melanoma • Oncology • Solid Tumor

Impact of NR4A3 on wound healing in chronic venous ulcers and its association with the PI3K/Akt signaling pathway. (PubMed, Front Physiol) - "PI3K/Akt agonist 740Y-P and inhibitor LY294002 were used in rescue experiments...These findings suggest that NR4A3 is associated with keratinocyte behavior and inflammatory responses via the PI3K/Akt pathway, potentially affecting chronic VU progression and healing. Reduced NR4A3 may impair wound repair through inflammation and abnormal cell migration, while TNF-α induces compensatory NR4A3 elevation."

Journal • Inflammation • Venous Ulcer • CXCL5 • CXCL8 • IL6 • NR4A3 • TNFA

Predicted mechanisms of Huaier in hepatocellular carcinoma therapy via IL-2/PI3K-Akt immunomodulation: An integrated multi-method study. (PubMed, J Ethnopharmacol) - "The findings suggest that combination therapy with Huaier may enhance the efficacy of conventional antitumor treatments against HCC, providing preliminary evidence for its clinical application. The immunomodulatory mechanism may involve the regulation of IL-2 expression through the PI3K-Akt pathway, as supported by computational predictions and preliminary in vitro validation at the transcriptional level. However, these mechanistic conclusions remain preliminary and require further confirmation through protein-level assays and more physiologically relevant in vivo models."

Journal • Hepatocellular Cancer • Immunology • Oncology • Solid Tumor • IL2 • IL6 • PIK3CA

HOXC9 promotes cell proliferation and suppresses mitochondria-dependent apoptosis through the AKT/mTOR pathway in esophageal squamous cell carcinoma. (PubMed, Mol Cell Biochem) - "Mechanistic studies were performed using RNA-seq, Western blotting, and PI3K inhibitor LY294002 (30 µM)...This study identifies a potential mechanism by which HOXC9 contributes to ESCC progression via AKT/mTOR-mediated inhibition of mitochondria-dependent apoptosis and promotion of cell proliferation. These findings suggest HOXC9 as a candidate prognostic biomarker and preliminary therapeutic target for ESCC, requiring further validation across clinical and molecular subtypes."

Journal • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma

Banxia Baizhu Tianma decoction inhibits neuronal cell death, inflammatory injury, and blood-brain barrier disruption after SAH via the PI3K-AKT pathway. (PubMed, Comput Biol Chem) - "BBTD confers neuroprotection against SAH by multi-target inhibition of programmed cell death, BBB disruption, and neuroinflammation, primarily via PI3K-AKT activation. This provides a foundation for preclinical evidence."

Journal • Cerebral Hemorrhage • Hematological Disorders • Inflammation • Subarachnoid Hemorrhage • ACSL4 • CASP3 • CASP7 • CASP8 • CASP9 • CLDN5 • GPX4 • MMP3 • NLRP3 • NOS3 • OCLN • RIPK1 • TJP1