Torin1 / InvivoGen - LARVOL DELTA

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

mTOR Signalling in Arbovirus Infections: Molecular Mechanisms and Therapeutic Opportunities. (PubMed, Rev Med Virol) - "Rapamycin and its derivatives reduce viral replication and improve survival in preclinical models, while repurposed drugs like niclosamide and chloroquine exhibit antiviral effects against ZIKV. ATP-competitive inhibitors such as Torin-1 and natural compounds like resveratrol expand the therapeutic landscape. Combination therapies pairing mTOR inhibitors with antivirals or immune modulators may provide synergistic benefits. This review highlights the molecular mechanisms underlying arbovirus manipulation of mTOR signalling and emphasises the potential of tailored therapeutic interventions targeting these pathways to mitigate arbovirus-associated diseases."

Journal • Review • CNS Disorders • Dengue Fever • Infectious Disease

Inactivation of mTOR is a strategy for tumor resistance to ribosome biogenesis inhibition (AACR 2025) - "The findings were validated using chemical inhibition of mTOR by Torin-1, a catalytic mTOR inhibitor and genetic knockout of an activator of mTOR signaling...In summary, we uncover a new non-genetic model of cancer drug resistance termed as translational fitness that enables cells to survive severe translational repression. These findings reveal an unexpected complication by mTOR inhibitory strategies and have implications for exploring effective drug combinations in cancer therapy."

Colorectal Cancer • Oncology • Solid Tumor

MLST8 overexpression in RPE cells disrupts autophagy through novel mechanisms affecting AMD pathogenesis. (PubMed, Autophagy) - "Using our uniquely developed MLST8 (MTOR associated protein, LST8 homolog) knock-in animal model with RPE-specific overexpression, which drives MTOR (mechanistic target of rapamycin kinase) upregulation, we demonstrate that increased MTOR complexes 1 and 2 in the RPE disrupts macroautophagy/autophagy by suppressing autophagosome formation genes and impairing MAP1LC3/LC3 processing. Notably, MTOR inhibition with torin1 treatment or CRYBA1 overexpression rescues these defects, restoring autophagy and RPE integrity. Our findings reveal that autophagy disruption mediated by both MTORC1 and MTORC2 drives AMD-like pathology in our mouse model, establishing autophagy regulation as a promising avenue for therapeutic intervention in this vision-threatening disease."

Journal • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Constitutive hepatic mTORC1 activation aggravates alcohol-induced liver injury via endoplasmic reticulum stress-mediated ferroptosis. (PubMed, Am J Pathol) - "Torin-1, an ATP-competitive mTOR inhibitor, suppressed the mTORC1 activity and reversed the effects of Depdc5 deletion on ER stress and ferroptosis in ethanol-fed mouse livers. Furthermore, pharmacological relief of ER stress using TUDCA or inhibition of ferroptosis with liproxstatin-1 both alleviated the liver abnormalities induced by Depdc5 ablation in ethanol-fed mice. Additionally, the research uncovered that ER stress functions as an upstream signal of ferroptosis in the progression of ALD. These findings provide novel in vivo evidence that sustained mTORC1 activation leads to alcoholic liver injury by inducing ER stress and ferroptosis, suggesting that targeting these pathways may represent a potential therapeutic strategy for ALD."

Journal • Fibrosis • Hepatology • Immunology • Liver Failure • DEPDC5

Activation of autophagy mediated by PI3K/Akt/mTOR signalling cascade alleviates impaired adipose-derived stem cell osteogenesis in a diabetic microenvironment. (PubMed, Br J Pharmacol) - "AGEs decreased the osteogenesis of ASCs by activating PI3K/Akt/mTOR signalling cascade and blocking autophagic flux. Autophagy induced by blocking the PI3K/Akt/mTOR signalling cascade could rescue the negative influences of ASCs in diabetic environment and provide a potential therapeutic strategy for bone renewal in individuals with DOP."

Journal • Osteoporosis • Rheumatology • RUNX2

Ribosome Profiling Reveals Translational Reprogramming via mTOR Activation in Omacetaxine Resistant Multiple Myeloma. (PubMed, Mol Cancer Res) - "Indeed, mTOR inhibition with Torin 1 restored partial sensitivity to omacetaxine in both resistant cell lines. These results provide a rational approach for omacetaxine-based combination in patients with multiple myeloma, which have historically shown better responses to multi-agent regimens. Implications: Through the use of ribosome profiling, our findings indicate mTOR inhibition as a novel combination therapy for partnering with the translation inhibitor omacetaxine in the treatment of multiple myeloma."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology

Autophagy regulates cellular senescence by mediating the degradation of CDKN1A/p21 and CDKN2A/p16 through SQSTM1/p62-mediated selective autophagy in myxomatous mitral valve degeneration. (PubMed, Autophagy) - "MTOR-dependent autophagy induced by rapamycin and torin-1 attenuated cell senescence and decreased the expression of cyclin-dependent kinase inhibitors (CDKIs) CDKN2A/p16INK4A and CDKN1A/p21CIP1...Notably, CDKN1A and CDKN2A localized to autophagosomes and lysosomes following MTOR antagonism or MG132 treatment...Our findings are the first demonstration that CDKN1A and CDKN2A are degraded through SQSTM1-mediated selective autophagy, independent of the ubiquitin-proteasome pathway. These data will inform development of therapeutic strategies for the treatment of canine and human MMVD, and for the treatment of Alzheimer disease, Parkinson disease and other age-related degenerative disorders."

Journal • Alzheimer's Disease • Cardiovascular • CNS Disorders • Movement Disorders • Parkinson's Disease • Targeted Protein Degradation • CDKN1A • CDKN2A • SQSTM1 • TGFB1

Activated mTOR Signaling in the RPE Drives EMT, Autophagy, and Metabolic Disruption, Resulting in AMD-Like Pathology in Mice. (PubMed, Aging Cell) - "The mechanistic target of rapamycin (mTOR) complexes 1 and 2 (mTORC1/2) are crucial for various physiological functions. Aging in these mice leads to RPE degeneration, causing retinal damage, impaired debris clearance, and metabolic and mitochondrial dysfunction. Inhibition of mTOR with TORIN1 in vitro or βA3/A1-crystallin in vivo normalized mTORC1/2 activity and restored function, revealing a novel role for the mTOR complexes in regulating RPE function, impacting retinal health and disease."

Journal • Preclinical • Age-related Macular Degeneration • Macular Degeneration • Metabolic Disorders • Ophthalmology • Retinal Disorders

An mTOR inhibitor discovery system using drug-sensitized yeast. (PubMed, Geroscience) - "Inhibition of the target of rapamycin (TOR/mTOR) protein kinase by the drug rapamycin extends lifespan and health span across diverse species...In contrast, 100 nM Torin1 and 500 nM GSK2126458 (omipalisib) are sufficient to identify TOR1-dependent growth inhibition in the drug-sensitized background...Additionally, for the TOR inhibitor AZD8055, the drug-sensitive system resolves that the compound results in TOR1-dependent growth sensitivity at 100 µM, whereas no growth inhibition is observed in a wild-type yeast strain background. Our platform also identifies the caffeine analog aminophylline as a TOR1-dependent growth inhibitor via selective tor1 growth sensitivity. We also tested nebivolol, isoliquiritigenin, canagliflozin, withaferin A, ganoderic acid A, and taurine and found no evidence for TOR inhibition using our yeast growth-based model. Our results demonstrate that this system is highly effective at identifying compounds that inhibit the TOR..."

Journal • Oncology