Ex-Rad (recilisib) / Traws Pharma - LARVOL DELTA

Effect of 6-gingerol on proliferation and apoptosis of ovarian cancer cells by the PI3K/AKT/mTOR pathway. (PubMed, Biochem Biophys Rep) - "SKOV3 ovarian cancer cells were treated with varying concentrations of 6-gingerol, either alone or in combination with Recilisib, an activator of the PI3K signaling pathway...The pivotal involvement of this signaling cascade is supported by the observation that its targeted activation effectively reverses the actions of 6-gingerol. Collectively, these results support further investigation into the biological effects of 6-gingerol in ovarian cancer models."

Journal • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • ATG7 • BECN1

Changyanqing decoction ameliorates ulcerative colitis via PI3K-Akt pathway: Insights from network pharmacology and in-vitro validation. (PubMed, Pak J Pharm Sci) - "CYQHJ exerts anti-inflammatory effects against UC mainly through PI3K-Akt inhibition, with quercetin as the core bioactive compound, providing mechanistic insight into its therapeutic action."

Journal • Preclinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • IL6 • TNFA

Aptamer-functionalized tetrahedral framework nucleic acid delivery of siBhlhe22 for repairing osteoporotic bone defects via dual modulation of PI3K-Akt signaling and purine metabolism. (PubMed, J Nanobiotechnology) - "This effect depended on the inhibition of PI3K-Akt signaling, as demonstrated by rescue experiments using the agonist Recilisib...This was accompanied by in vivo suppression of PI3K-Akt signaling and upregulation of OCN and OPN. Our findings establish a novel gene therapy strategy that targets Bhlhe22 to simultaneously modulate pro-osteogenic signaling and metabolic reprogramming, offering a promising anabolic approach for osteoporosis treatment."

Journal • Gene Therapies • Osteoporosis • Rheumatology • RUNX2

Liensinine induces autophagy and apoptosis in hepatocellular carcinoma via reactive oxygen species-mediated inhibition of the PI3K/AKT/mTOR pathway. (PubMed, Tissue Cell) - "Lien exerts anti-HCC effects by promoting autophagy and apoptosis through ROS-mediated inhibition of the PI3K/AKT/mTOR pathway."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • BECN1

Pharmacological Potential of Gardoside in Anxiety: Behavioral and Molecular Evidence. (PubMed, J Ethnopharmacol) - "GS can significantly alleviate FS-induced anxiety-like behavior in mice, and its mechanism of action may be related to inhibiting the excessive activation of the PI3K/AKT signaling pathway in the hippocampus, thereby regulating glutamate receptor function and reducing neuronal excitability. Our study provides an important pharmacological basis for the development of GS as a potential anti-anxiety drug."

Journal • Mood Disorders • Psychiatry • EGFR • PIK3R1

Quercetin Ameliorates Comorbid Insomnia in Diarrhea-Predominant Irritable Bowel Syndrome via the PI3K/AKT/NF-κB Signaling Pathway. (PubMed, Biomedicines) - "Experimental validation was conducted in 36 male C57BL/6J mice assigned to control, CID+IBS-D model, quercetin-treated, and quercetin-plus-Recilisib-treated groups...The protective effects were associated with reduced inflammatory activation and modulation of PI3K/AKT/NF-κB-related signaling. These findings support quercetin as a promising candidate for gut-brain axis-related comorbid disorders, while further studies are needed to define pathway specificity, tissue exposure, and translational applicability."

Journal • CNS Disorders • Gastrointestinal Disorder • Immunology • Inflammation • Insomnia • Sleep Disorder • OCLN • TJP1

Niranthin ameliorates Crohn's disease-like colitis in mice via antagonizing intestinal epithelial cell apoptosis and regulating intestinal Th1/Th2 immune homeostasis (PubMed, Nan Fang Yi Ke Da Xue Xue Bao) - "Niranthin ameliorates colitis in mice by antagonizing epithelial apoptosis and regulating Th1/Th2 balance via inhibiting the PI3K/AKT pathway."

Journal • Preclinical • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • BAX • BCL2 • CASP3 • CLDN1 • IL10 • TJP1 • TNFA

Blockade of T-type Ca2+ channels disrupts mitochondrial function and follicle development by inhibiting the PI3K/AKT pathway. (PubMed, Reproduction) - "To investigate this, we administered flunarizine (FNZ), a potent T-type VGCCs antagonist, to 4-6-week-old female mice via intraperitoneal injection at doses of 0, 3, or 30 mg/kg/day for 7 days. Furthermore, FNZ inhibit activation of protein kinase B (p-AKT), an effect that was rescued by recilisib, a specific activator of phosphatidylinositol 3-kinase (PI3K)/AKT. In conclusion, our study establishes that pharmacological inhibition of T-type VGCCs disrupts hormonal secretion and follicular development in adolescent mice, likely through modulation of the PI3K/AKT signaling axis."

Journal • Metabolic Disorders

Single-Nucleus RNA Sequencing Reveals SPP1+ Macrophages Induce Cardiomyocyte Apoptosis to Promote Atrial Fibrillation Susceptibility. (PubMed, J Cardiovasc Dev Dis) - "Treatment with the PI3K/AKT activator Recilisib reversed apoptosis and restored p-PI3K/p-AKT levels in HL-1 cells co-cultured with SPP1-overexpressing RAW264.7 macrophages. These findings demonstrate that SPP1+ macrophages accumulate in atrial tissues of AF patients and induce cardiomyocyte apoptosis by downregulating the PI3K/AKT pathway, thereby increasing AF susceptibility."

IO biomarker • Journal • Atrial Fibrillation • Cardiovascular • Heart Failure • BCL2 • CASP3 • SPP1

Structural maintenance of chromosome protein 1A exacerbates liver fibrosis by enhancing hepatic stellate cell activation and extracellular matrix synthesis via laminin subunit gamma 2 activation. (PubMed, J Cell Commun Signal) - "Rescue experiments were conducted in sh-LAMC2-treated and recilisib (PI3K/Akt agonist)-treated mice...The inhibitory effect of SMC1A knockdown on ECM accumulation and HSC activation was mitigated by LAMC2 overexpression. This study provides new insights and highlights the promising potential of the SMC1A/LAMC2/PI3K/Akt axis as a therapeutic target for liver fibrosis."

Journal • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • LAMC2 • SMC1A

m6A-mediated stabilization of Bhlhe22 suppresses osteogenesis in osteoporosis by activating the PI3K-AKT-GSK3β signaling axis. (PubMed, Stem Cell Res Ther) - "m6A modification stabilizes Bhlhe22 mRNA, leading to its overexpression in OP. Elevated BHLHE22 protein suppresses BMSC osteogenesis by transcriptionally activating Pik3r3 and the PI3K-AKT-GSK3β signaling axis. Targeting the m6A-Bhlhe22-PI3K axis represents a promising therapeutic strategy for osteoporosis."

Journal • Osteoporosis • Rheumatology • GSK3B • PIK3R3

Berberine-cinnamic acid co-crystal effect in ameliorating hyperlipidemia might be regulated through the PI3K/AKT/mTOR/SREBP-1 signaling pathway. (PubMed, FEBS Open Bio) - "Furthermore, the phosphorylation of phosphatidylinositol 3-kinase (PI3K), AKT and mammalian target of rapamycin (mTOR) was inhibited by BBR-CA, contributing to decreased active SREBP-1 in the nucleus, and was reversed and enhanced by the PI3K agonist recilisib and inhibitor LY294002, respectively. Taken together, our results suggest that BBR-CA could function by modulating the PI3K/AKT/mTOR signaling pathway, resulting in decreased nuclear expression of SREBP-1, as well as reduced expression of stearoyl-CoA desaturase 1 and acetyl-CoA carboxylase, thus alleviating hyperlipidemia. Further experimental validation is required to confirm these results."

Journal • Dyslipidemia • Hepatocellular Cancer • Oncology • Solid Tumor • SCD

Dendrobin A inhibits gastric cancer: Mechanistic insights supported by integrated evidence. (PubMed, Phytomedicine) - "Dendrobin A exerts potent anti-GC effects by inhibiting HSP90AB1/CDK2/PARP1 expression and modulating P53/PI3K-Akt signaling, supporting its therapeutic potential."

Journal • Gastric Cancer • Oncology • Solid Tumor • CDC37 • CDKN1A • HSP90AB1

Sappanone A, a potential natural inhibitor of PI3K, alleviates metabolic dysfunction-associated steatohepatitis in experimental models. (PubMed, Biochem Pharmacol) - "Network pharmacology results indicated that SA might alleviate MASH through the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/(Mechanistic target of rapamycin) mTOR signaling pathway. Notably, the PI3K activator Recilisib weakened the inhibitory effect of SA on PA-induced p-AKT and COL1a1 in LX-2 cells, further confirming the dependence of SA on PI3K activity. In conclusion, we identified SA as a potential natural PI3K inhibitor and promising compound for the treatment of MASH."

Journal • Fibrosis • Hepatocellular Cancer • Hepatology • Immunology • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Oncology • Solid Tumor • COL1A1

Mechanistic Insights into AKT1/GSK3β/CD36 Axis Regulation in ZLY06-Induced Hepatic Lipid Metabolism Dysfunction and Protective Intervention via AKT Activation Strategies. (PubMed, Food Chem Toxicol) - "Experimental evidence demonstrated that AKT activators (such as SC79 and Recilisib) mitigated ZLY06-induced lipid accumulation by restoring AKT1 phosphorylation, reducing CD36 expression, and normalizing lipid metabolism. These findings provided critical mechanistic insights into ZLY06-induced hepatotoxicity and suggested a potential therapeutic strategy to alleviate hepatic lipid accumulation through AKT pathway activation. This work advances our understanding of drug-induced hepatic lipid metabolism disorders and lays a foundation for the development of safer therapeutic agents."

Journal • Dyslipidemia • Metabolic Disorders • CD36 • GSK3B • SCARB1

PI3K-Mediated Regulation of Glycogen Metabolism To Facilitate Tomato chlorosis Virus Transmission by Bemisia tabaci MED. (PubMed, J Agric Food Chem) - "Similarly, feeding whiteflies with the PI3K inhibitor PI3K-IN-1 decreased ToCV transmission, while the PI3K activator Recilisib enhanced it...Conversely, the inhibition of PI3K disrupts glycogen metabolism, consequently impairing viral transmission. These findings highlight that PI3K is crucial for facilitating ToCV transmission by whiteflies and offer a potential target for controlling vector-borne plant viruses."

Journal

Discovery of a novel quinoxaline derivative modulator via a dual P53/TLR2 targeting strategy for the alleviation of radiation damage. (PubMed, Eur J Med Chem) - "In this study, a series of novel quinoxaline molecules were designed and synthesized with Ex-RAD and TLR2 agonist as the lead, showing anti-radiation effects and compound Z9 was the best one of them...Notably, Z9 showed excellent stability and affinity for the TLR2 protein conjugate in molecular docking and molecular dynamics simulations. These findings suggested that Z9 was worth further research being a potential candidate for anti-radiation drugs, as the dual modulator of P53/TLR2."

Journal • BAX • MYD88 • TLR2

Curcumol attenuates hyperproliferation and inflammatory response in a psoriatic HaCaT keratinocyte model by inhibiting the PI3K-Akt pathway and ameliorates skin lesions and inflammatory status in psoriasis-like mice. (PubMed, Inflammopharmacology) - "Additionally, in vivo, curcumol ameliorates psoriasis-like skin lesions and inflammatory status in imiquimod-induced mice. Further investigation shows that curcumol partially counteracts the activation of PI3K-Akt by recilisib in keratinocytes. These results suggest that curcumol may be a promising therapeutic option for psoriasis."

Journal • Preclinical • Dermatology • Immunology • Inflammation • Psoriasis

Asperosaponin VI alleviates TNBS-induced Crohn's disease-like colitis in mice by reducing intestinal epithelial cell apoptosis via inhibiting the PI3K/AKT/NF-κB signaling pathway (PubMed, Nan Fang Yi Ke Da Xue Xue Bao) - "AVI can improve TNBS-induced CD-like colitis in mice by reducing intestinal epithelial cell apoptosis and intestinal barrier damage via inhibiting the PI3K/AKT/NF-κB signaling pathway."

Journal • Preclinical • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease

Design, synthesis and biological evaluation of (E)-kojyl-styryl-sulfones: Novel recilisib hybrids as promising radioprotectors. (PubMed, Arch Pharm (Weinheim)) - "Moreover, the antioxidant evaluation of these selected hybrids on the IR-induced reactive oxygen species (ROS) generation and lipid peroxidation in the HFF-1 cells revealed that they could significantly downregulate IR-induced oxidative stress in the HFF-1 cells, while mechanistically recilisib is not a well-established ROS scavenger. The obtained results suggest that these privileged (E)-kojyl-styryl-sulfones can serve as promising radioprotectors for further studies and development."

Journal

HYPOCRELLIN A, A NATURAL SMALL COMPOUND, EXERTS ANTI-TUMOR EFFECTS VIA MULTI-TARGET INHIBITION OF THE PI3K-AKT-MTOR, MAPK, AND STAT3 SIGNALING PATHWAYS IN INTRAHEPATIC CHOLANGIOCARCINOMA (AASLD 2024) - "This inhibitory effect can be rescued by recilisib, an activator of PI3K-AKT-mTOR... HA demonstrated promising therapeutic efficacy against ICC through its multi-target inhibition effects on the PI3K-AKT-mTOR, MAPK, and STAT3 signaling pathways. Moreover, it exhibited notable therapeutic benefits in primary ICC model (KRAS/P19/SB), positioning it as a novel therapeutic agent for treating ICC."

Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • KRAS

Hypocrellin A against intrahepatic Cholangiocarcinoma via multi-target inhibition of the PI3K-AKT-mTOR, MAPK, and STAT3 signaling pathways. (PubMed, Phytomedicine) - "HA, a novel natural small molecule, demonstrated promising therapeutic efficacy against ICC through its multi-target inhibitory effects on the PI3K-AKT-mTOR, MAPK, and STAT3 signaling pathways. Moreover, it exhibited notable therapeutic benefits in a primary ICC model (KRAS/P19/SB), positioning it as a novel therapeutic agent for ICC."

Journal • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • KRAS

MG-132 activates sodium palmitate-induced autophagy in human vascular smooth muscle cells and inhibits senescence via the PI3K/AKT/mTOR axis. (PubMed, Lipids Health Dis) - "MG-132 activates autophagy by inhibiting the PI3K/AKT/mTOR pathway, thereby inhibiting palmitate-induced proliferation, migration, and oxidative stress in vascular smooth muscle cells and suppressing their senescence."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • BECN1

New mechanistic understanding of osteoclast differentiation and bone resorption mediated by P2X7 receptors and PI3K-Akt-GSK3β signaling. (PubMed, Cell Mol Biol Lett) - "P2X7 receptors positively regulate osteoclast formation and bone resorption by activating the PI3K-Akt-GSK3β signaling pathway."

Journal • Metabolic Disorders • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Rheumatology • CSF1 • GSK3B • MMP9 • NFATC1 • TNFRSF11A • TRAP

FNDC5 inhibits malignant growth of human cervical cancer cells via restraining PI3K/AKT pathway. (PubMed, J Cell Physiol) - "The effects of FNDC5 were prevented by inhibiting integrin with cilengitide, activating PI3K with recilisib or activating Akt with SC79...PI3K inhibitor LY294002 showed similar effects to FNDC5 in HeLa and SiHa cells...These results indicate that FNDC5 inhibits the malignant phenotype of CxCa cells through restraining PI3K/Akt signaling. Upregulation of FNDC5 may play a beneficial role in retarding the tumor growth of CxCa."

Journal • Cervical Cancer • Oncology • Solid Tumor