Torin1 / InvivoGen - LARVOL DELTA

mTORC1 Signaling Mediates Epithelial Dysfunction in Eosinophilic Chronic Rhinosinusitis with Nasal Polyp (eCRSwNP). (AAAAI 2026) - "mTORC1 signaling mediates BC hyperplasia and barrier disruption in TGF-β treated ALI cultures from eCRSwNP patients."

Chronic Rhinosinusitis With Nasal Polyps • Immunology • Nasal Polyps • Otorhinolaryngology • Respiratory Diseases • Sinusitis • CDH1 • CLDN1 • TGFB1

AMPK promotes TFEB transcriptional activity through dephosphorylation at both MTORC1-dependent and -independent sites. (PubMed, Autophagy) - "Treatment of cells with an AMPK activator (MK-8722), glucose deprivation or MTOR inhibitor (torin1) robustly dephosphorylated TFEB not only at the MTORC1-targeted N-terminal serine sites, but also at the C-terminal sites. Loss of function of AMPK abrogated MK-8722- but not torin1-induced dephosphorylation and induction of the TFEB target genes."

Journal • AMPK • TFEB

Florasulam impairs Leydig cell function by blocking autophagic flux and triggering PERK-eIF2α-ATF4-CHOP-mediated ER stress. (PubMed, Ecotoxicol Environ Saf) - "Pharmacological restoration of autophagy with Rapamycin or Torin1 attenuates ER stress and significantly reduces apoptosis. These results identify a critical autophagy-ER stress axis underlying Florasulam-induced Leydig cell injury and provide mechanistic insight into the reproductive risks associated with herbicide exposure."

IO biomarker • Journal • ATF4 • BCL2

A Zebrafish Seizure Model of cblX Syndrome Reveals a Dose-Dependent Response to mTor Inhibition. (PubMed, J Dev Biol) - "We employed a two-concentration model of the seizure-inducing agent, pentylenetetrazol (PTZ), with or without pretreatment of the mTor inhibitor, torin1...These data suggest that inhibition of mTor in an hcfc1a-deficient background leads to a reaction that differs from the traditional response observed in wildtype siblings. Collectively, we present a model that can be used to test dose-response and the development of combinatorial treatment approaches in a high-throughput manner."

Journal • CNS Disorders • Developmental Disorders • Epilepsy • Genetic Disorders • Mental Retardation • Metabolic Disorders • HCFC1

Effects and mechanisms of core formula improving glomerulosclerosis in diabetic kidney disease by Jinling medical school based on "reticulophagy-PANoptosis" signaling pathway in podocyte (PubMed, Zhongguo Zhong Yao Za Zhi) - "After modeling successfully, the DKD rat models received either TCF, empagliflozin(EMPA), or saline by gavage for 8 weeks, respectively. Secondly, MPC5 cells were subjected to treatment under high-glucose(HG) conditions alone, or HG combined individually with drug-containing serum of the low-dose of TCF(L-TCF) and the high-dose of TCF(H-TCF), EMPA, or Torin 1(autophagy agonist)...The in vitro study results showed that, high and low doses of TCF and EMPA both could ameliorate the protein expression levels of key signaling molecules in the PANoptosis pathway in podocytes treated with HG, and the improvement effect of H-TCF was superior to that of L-TCF or EMPA. In conclusion, the study clarifies that TCF improves GS in DKD by regulating ER-phagy-PANoptosis signaling pathway in podocytes in vivo and in vitro, and has laid the groundwork for exploring mechanisms and scientific implications of treating diabetic kidney disease by Jinling medical school."

Journal • Diabetes • Diabetic Nephropathy • Glomerulonephritis • Nephrology • Renal Disease • IGF2BP1 • IL18 • ZBP1

Chaperone-mediated autophagy ameliorates hyperlipidemia-induced apoptosis in podocytes via attenuating lipid accumulation. (PubMed, J Mol Histol) - "We further found that blocking CMA with inhibitor VER155008 or LAMP-2 A siRNA significantly upregulated PA-induced increased expression of PLIN2, exacerbated PA-induced lipid accumulation and apoptosis, whereas promoting CMA with Torin1 downregulated the expression of PLIN2, ameliorated lipid accumulation and apoptosis in PA-induced podocytes. Moreover, we also observed the activation of CMA and increased lipid accumulation in the kidney tissue of DKD mice. Taken together, these results suggest that CMA plays a protective role in PA-induced podocytes apoptosis and that the potential protective mechanism of CMA is involved in reducing cellular lipid accumulation through mediating the degradation of PLIN2."

Journal • Diabetic Nephropathy • Dyslipidemia • Metabolic Disorders • Nephrology • Renal Disease • PLIN2

TSC2 is a positive master regulator of cellulase production by affecting protein secretion in Trichoderma reesei. (PubMed, Int J Biol Macromol) - "The mTOR inhibitor Torin 1 significantly inhibited the production of CMC and BGL at the early stage...Autophagy inhibition via ammonium chloride or atg8 deletion suppressed cellulase yields. These findings suggest that the TSC2-mTORC1-GRASP55-autophagy signaling axis may govern the secretion of cellulase components BGL and CMC, playing a crucial role in cellulase production in T. reesei."

Journal • TSC2

Untargeted metabolomics and lipidomics to study autophagy induction in mouse embryonic fibroblasts. (PubMed, Anal Bioanal Chem) - "Together, these results show that Torin1 and Tat-Beclin1 trigger distinct yet partly overlapping metabolic programs. The metabolic signatures identified here provide reference profiles for future mechanistic studies and highlight candidate biomarkers that may support early functional evaluation of autophagy modulators in disease-relevant settings."

Journal • Preclinical • BECN1

Menin-driven mTOR signaling sustains taxane resistance in CRPC and reveals a targetable vulnerability for combination therapy. (PubMed, Cell Commun Signal) - "While taxanes such as docetaxel (Dtx) and cabazitaxel (Cbz) are widely employed, therapeutic resistance remains a major clinical obstacle...Moreover, combination treatment with the mTOR inhibitor Torin-1 and docetaxel synergistically enhanced therapeutic response in Menin-depleted resistant cells. MEN1 knockdown also abrogated tumor growth in vivo.These findings identify Menin as one of the key mediator of taxane resistance in CRPC through the regulation of mTOR. Targeting Menin, alone or in combination with mTOR inhibition, represents a promising strategy to overcome resistance and improve therapeutic outcomes in taxane-refractory PC."

Journal • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CCND1 • MEN1 • WDR5

mTOR Activation Causes Cellular Aggregation and Proteomic Changes in vitro (AES 2025) - "Treatment groups included mTOR inhibitors rapamycin (50 nM; 48hrs) or torin1 (50 nM; 48 hrs), or physiological media only. Abnormal cellular aggregation is an mTOR-dependent phenotype that occurs in vitro, following Nprl3, Tsc2, Strada, or Kptn KO. Changes in the proteome in vitro point towards both overlapping and unique mechanisms of cell aggregation across human mTORopathies. These observations suggest enhanced cellular aggregation caused by mTOR hyperactivation as a common phenotype that may play contribute to histological features seen in mTORopathies."

Preclinical • CNS Disorders • Epilepsy

Lipocalin-2 Is Induced by Uromodulin Aggregates but Does Not Affect Kidney Disease Progression in UMOD-Related Autosomal Dominant Tubulointerstitial Kidney Disease (KIDNEY WEEK 2025) - "LCN2 induction by specific mutant uromodulin aggregates was confirmed in the mIMCD3 cells, with a significant rescue observed when stimulating aggregate clearance with Torin-1...Conclusion These findings identify LCN2 as a mutation-specific tubular stress marker in ADTKD- UMOD , strongly induced by intracellular accumulation of mutant uromodulin in TAL cells. While LCN2 contributes to iron handling, it does not drive fibrosis nor inflammation in the mutant kidneys, supporting its potential utility as a disease biomarker rather than a therapeutic target."

Fibrosis • Immunology • Inflammation • Nephrology • Renal Disease • LCN2 • UMOD

CXCL3 promotes liver cancer progression by modulating the tumor microenvironment via the PI3K/AKT/mTOR pathway. (PubMed, PLoS One) - "Mechanistically, CXCL3 activated the PI3K/AKT/mTOR pathway by upregulating PI3K, p-PI3K, AKT, p-AKT, mTOR, and p-mTOR, while the mTOR inhibitor Torin 1 reversed these effects...In vivo, CXCL3 overexpression significantly promoted tumor growth in nude mice. These findings suggest CXCL3 facilitates liver cancer progression through tumor microenvironment modulation and PI3K/AKT/mTOR pathway activation."

Biomarker • IO biomarker • Journal • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • CXCL3

Lysosomal homeostasis regulates myocardial ischemia-reperfusion injury through autophagy pathway. (PubMed, Sci Rep) - "Using a rat MIRI model and primary myocardial cell hypoxia/reoxygenation (HR) model, we assessed the changes in autophagic flux through the intervention of autophagy agonists (TAT-Beclin1), inhibitors (3-MA), lysosomal agonists (Torin1), and inhibitors (Bafilomycin A1) from multiple dimensions...This study reveals a vicious cycle of “overactivation of autophagy - lysosomal degradation defects” in MIRI, and targeting lysosomal homeostasis to regulate autophagic flux may serve as a novel therapeutic strategy. The online version contains supplementary material available at 10.1038/s41598-025-20853-6."

Journal • Cardiovascular • Myocardial Ischemia • Reperfusion Injury • ANXA5 • BECN1 • LAMP1 • SQSTM1

Lamprey TFE3 exhibits evolutionarily conserved activation mechanisms and regulates autophagy and immune responses. (PubMed, Dev Comp Immunol) - "Treatment with Torin1 induced nuclear translocation of TFE3, indicative of its activation...In vivo stimulation with LPS or poly (I:C) induced significant changes in Lj-TFE3 expression, indicating that lamprey TFE3 is responsive to pathogen-associated molecular patterns and may participate in immune stress responses. Together, these findings demonstrate that lamprey TFE3 exhibits conserved structural and functional features and plays a key role in immune and metabolic regulation, providing important evolutionary insights into the MiT/TFE transcription factor family in early vertebrates."

Journal • Inflammation • Ophthalmology • ABCA1 • MITF • TFE3 • TFEB

Persistent mTORC1 activation underlies sex dimorphic progression of MASLD in mice with hepatocyte prohibitin-1 deficiency. (PubMed, Res Sq) - "Prior studies in disparate cell models have implicated PHB1 as a mediator of insulin signaling and its downstream effector, the mechanistic target of rapamycin complex 1 (mTORC1), but the mechanisms and physiological implications of these interactions are unclear. Furthermore, one week of treatment with mTORC1 inhibitor Torin1 reduced hepatic triglycerides and normalized mTORC1 signaling in hPHB1-KD males to levels comparable with WT. Collectively, these findings demonstrate that PHB1 is essential for maintaining metabolic homeostasis in liver via control of mTORC1-lipin1 axis, and further confirm that metabolic effects of PHB1 deficiency in liver are sexually dimorphic."

Journal • Preclinical • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • EIF4EBP1 • LPIN1

Rapalink-1 reveals TOR-dependent genes and an agmatinergic axis-based metabolic feedback regulating TOR activity and lifespan in fission yeast. (PubMed, Commun Biol) - "The Target of Rapamycin, TOR, is a conserved signalling pathway with characterised chemical inhibitors such as rapamycin and torin1. Genetic interactome assays for the agmatinase agm1 and further cell and molecular analyses demonstrate that impairing the agmatinergic branch of arginine catabolism results in TOR activity levels that are beneficial for growth but detrimental for chronological ageing. Our study reveals the anti-ageing action of agmatinases within a metabolic circuit that regulates TOR activity, protein translation levels and lifespan."

Journal

Counteracting lysosome defects alleviates the cellular senescence of Hutchinson-Gilford progeria syndrome. (PubMed, Sci China Life Sci) - "Activating lysosome biogenesis via the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) or the mTORC1 inhibitor Torin 1 promoted progerin clearance and accordingly mitigated DNA damage, cell cycle arrest, low proliferation ability and senescence-associated secretory phenotype (SASP) in HGPS cells. Overall, we propose that, in HGPS, lysosomes exhibit defects and that activating lysosome biogenesis can accelerate progerin clearance and alleviate cellular senescence. These findings highlight the anti-senescence roles of PKC activation and lysosome biogenesis and provide new insights for understanding and treating HGPS."

Journal • LMNA

Comprehensive bioinformatic analysis identifies potential therapeutic drugs for CryAB (R120G)-related cardiomyopathy. (PubMed, BMC Cardiovasc Disord) - "By using Connectivity Map (CMap) analysis and transcriptome data, we identified phosphodiesterase (PDE) family as potential targets and several potential therapeutic candidates, with nortriptyline, torin-1, and cilostazol emerging as top candidates. Molecular docking simulations showed that Nortriptyline exhibited strong binding affinities with hub proteins, particularly SCN5A. These findings suggest promising new therapeutic strategies for CryAB(R120G)-related cardiomyopathy by targeting specific pathways and hub genes to mitigate cardiac dysfunction."

Journal • Cardiomyopathy • Cardiovascular • ACACB • CRYAB • RPA1

CD4+ differentiated T regulatory cells is modified by physical fitness and visceral adipose tissue in young adults-A cross-sectional study. (PubMed, Physiol Rep) - "CD4+ cells were cultured in Treg differentiation medium with 2 ng/mL TGF-β, with or without 100 nM rapamycin or 50 nM Torin-1, for 96 h. These findings indicate that low cardiorespiratory fitness and high VAT contribute to an altered inflammatory response, influencing peripheral blood mononuclear cell immunophenotypes and exhaustion markers. Furthermore, mTORC1 and mTORC2 inhibition modulate cytokine production, emphasizing the role of metabolic status in immune regulation."

Journal • Observational data • Genetic Disorders • Inflammation • Obesity • CD4 • IL10 • IL6 • TGFB1

PTEN deficiency in postnatally developing Purkinje cells disrupts metabolic signaling, leading to dendritic abnormalities and sex-specific behavioral deficits. (PubMed, Sci Rep) - "Notably, ex vivo treatment with AICAR (an AMPK activator) or Torin1 (an mTOR inhibitor) partially restored dendritic organelle content in Pten-deficient PCs. These findings suggest that PTEN is critical for maintaining metabolic balance during postnatal dendritic maturation, and its loss leads to structural and functional impairments in PCs that contribute to behavioral phenotypes in a sex- and age-dependent manner."

Journal • Autism Spectrum Disorder • CNS Disorders • Genetic Disorders • Metabolic Disorders • PTEN

Dissecting the cell cycle regulation, DNA damage sensitivity and lifespan effects of caffeine in fission yeast. (PubMed, Microb Cell) - "We have previously suggested that caffeine modulates cell cycle progression and lifespan by inhibiting the Target of Rapamycin Complex 1 (TORC1)...Our findings show that caffeine accelerates mitotic division and is beneficial for CLS through AMPK. Direct pharmacological targeting of AMPK may serve towards healthspan and lifespan benefits beyond yeasts, given the highly conserved nature of this key regulatory cellular energy sensor."

Journal

A newly discovered mTOR-STAT3 pathway regulates calcium release and calcium-mediated apoptosis at the ER in Triple Negative Breast Cancer (EACR 2025) - "Pan-mTOR inhibition by Torin-1 – but not mTOR Complex 1 inhibition via Rapamycin – could prevent both IP3R3 degradation and Ca2+-mediated apoptosis, mimicking the effects of STAT3 silencing. These data demonstrate for the first time that STAT3 Serine phosphorylation can be regulated in the specific cellular compartment where its functions are exerted, in this case occurring at the ER downstream of mTOR. In turn this specific regulation can lead to enhance apoptosis resistance via IP3R3 degradation. Preliminary data indicate that STAT3-mTOR might directly interact, since they can still co-immunoprecipitate in the absence of either mTORC1 or mTORC2 upon RAPTOR and RICTOR ablation, respectively."

Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • AKT1 • RICTOR • STAT3

Autophagy-dependent hepatocyte apoptosis mediates gilteritinib-induced hepatotoxicity. (PubMed, Toxicol Lett) - "Pharmacological inhibition of autophagy with autophagy inhibitor 3-methyladenine (3-MA, 5mM) or gene silence of Atg7 attenuated apoptosis, mitochondrial membrane potential loss, and ROS overproduction, while autophagy induction by Torin1 (100nM) exacerbated hepatocyte death. Targeting autophagy pathways, represents a potential therapeutic strategy to alleviate gilteritinib-induced hepatotoxicity, enabling safer clinical use of this vital AML therapy. This study elucidates a critical autophagy-apoptosis axis in drug-induced liver injury and provides actionable insights for managing adverse effects of targeted cancer therapies."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Hepatology • Leukemia • Liver Failure • Oncology • ANXA5 • ATG7 • CASP3 • FLT3

Torin-1 improves cognitive decline by regulating autophagic system and cholesterol metabolism in hepatic encephalopathy. (PubMed, Exp Neurol) - "Conclusively, these findings indicate that the induction of autophagy was found to alleviate the adverse effects seen in HE by regulating cholesterol metabolism in the cerebral cortex. The autophagy inducer torin-1 might be a potential approach to alleviate alterations and symptoms in HE."

Journal • CNS Disorders • Cognitive Disorders • Fibrosis • Gastroenterology • Hepatic Encephalopathy • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Liver Failure • Metabolic Disorders • CLSPN,

Beta cells intrinsically sense and limit their secretory activity via mTORC1-RhoA signaling. (PubMed, Cell Rep) - "Here, we show that the nutrient sensor mechanistic Target of Rapamycin Complex 1 (mTORC1) is rapidly activated by glucose in β cells via the insulin secretion machinery, positioning mTORC1 as a sensor of β cell activity...Mechanistically, mTORC1 promotes RhoA activation and F-actin polymerization, limiting vesicle movement and dampening the second phase of insulin secretion. These findings identify a glucose-mTORC1-RhoA signaling axis that forms an autonomous feedback loop to constrain insulin exocytosis, providing insight into how β cells prevent excessive insulin release and maintain metabolic balance."

Journal • RHOA