tideglusib (AMO-02) / AMO Pharma, ASD Therap - LARVOL DELTA

Tideglusib as a First-in-Class Chemical Probe for NatA: Identification, Mechanism, and Cellular Validation of an Allosteric, CoA-Dependent Inhibitor. (PubMed, ACS Chem Biol) - "Quantitative proteomics confirmed on-target suppression of NatA-mediated Nα-acetylation in yeast. These findings establish tideglusib as a mechanistic chemical probe for NatA, reveal NatA as a previously unrecognized molecular target for a promiscuous clinical-stage investigational compound, and introduce a conceptual framework for exploiting catalysis-dependent adduct formation as a new strategy for acetyltransferase inhibitor design."

Journal

Tideglusib-Preactivated Osteoblasts Encapsulated in Ceramic Particle-Reinforced GelMA Hydrogel for Enhanced Critical-Size Bone Defect Regeneration. (PubMed, Drug Des Devel Ther) - "The composite BCP particle/GelMA scaffold with Tideglusib-pretreated OBs provides mechanical reinforcement and sustained osteogenic stimulation, effectively accelerating critical-size bone defect regeneration. This ex vivo pharmacological priming strategy represents a promising translational approach for bone tissue engineering."

Journal

BDNF and GSK-3β signaling in depression: molecular mechanisms underlying neural plasticity dysfunction. (PubMed, Mol Biol Rep) - "It further illustrates emerging therapeutic approaches targeting this axis, such as metformin, famotidine, tideglusib, lithium, and ketamine. Collectively, the altered crosstalk between BDNF and GSK-3β contributes to the impaired neuroplasticity observed in depression, suggesting that this signaling axis is a promising therapeutic target."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Depression • Inflammation • Mood Disorders • Psychiatry • GSK3B

MicroRNA Biomarkers For ALS: From Systems Biology To Patient Derived Cells (ENCALS 2026) - "Among the pharmacological treatments, IGS2.7 totally restored miR‑206 levels in SOD1 cells and partially miR‑192‑5p levels in sALS cells whereas Tideglusib modulated only miR-1-3p levels in sALS cells. Conclusion Our approach integrating PPIn and experimentally validated interactions between miRNAs and genes revealed a robust framework for the discovery of new biomarkers in ALS. miR‑192‑5p, miR‑1-3p and miR‑206 emerge as promising biomarkers due to their consistent reduction in sALS and/or SOD1 models, with its additional possible relevance for therapeutic monitoring."

Biomarker • Clinical • MIR192 • MIR206 • SOD1

AMO Pharma Limited…announced agreement with regulatory agencies in the U.S., U.K. and Canada on design for a registrational clinical study intended to assess the safety and efficacy of the Company's investigational therapy AMO-02 (oral tideglusib) in the treatment of congenital myotonic dystrophy type 1 (cDM1) (PRNewswire) - "The design requirements and primary outcome choice for this registrational study are based on advice provided to AMO Pharma by the U.S. Food and Drug Administration (FDA), the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) and Health Canada following meetings over the last six months....Based on this regulatory advice, the registrational study for AMO-02 is expected to use hospitalization as the primary efficacy endpoint....The Company expects to provide an update on the planned initiation of the study during the third quarter of 2026."

New trial • Regulatory • Myotonic Dystrophy

Single molecule, dual actions: GSK-3β/AChE dual inhibition for Alzheimer's disease. (PubMed, Eur J Med Chem) - "Our previous work verified that GL10a displayed superior GSK-3β inhibitory and neuroprotective activities relative to Tideglusib. Accordingly, a molecular hybridization strategy was applied to design and synthesize a series of dual target inhibitors against GSK-3β and AChE by conjugating GL10a and carbamate fragment of Rivastigmine's pharmacophore...With favorable pharmacokinetic characteristics and tissue distribution, AJ-4 obviously ameliorated scopolamine-induced learning and memory impairments and alleviated hippocampal neuronal injury in AD mice. In conclusion, GSK-3β/AChE dual inhibitors represent a promising strategy for developing multi-target anti-AD drugs."

Journal • Alzheimer's Disease • CNS Disorders • Pain • APP

Tideglusib-loaded hyaluronic acid hydrogels enhance odontogenic differentiation with adjunct low-intensity focused ultrasound. (PubMed, Dent Mater) - "Sustained Tideglusib delivery from HA-MA hydrogels with LIFU stimulation supported odontogenic differentiation and mineralized matrix formation in hDPSCs. This strategy may offer a platform for biologically driven dentin-pulp repair and dentin-pulp complex regeneration."

Journal • BMP2

Tideglusib improves novel object recognition memory in the preclinical DBA/2J mdx mouse model of Duchenne muscular dystrophy. (PubMed, Front Neurosci) - "While there were no changes in BACE1 activity, tideglusib-treated mdx mice had higher concentrations of Aβ in the serum and lower protein levels of receptor of advanced glycation end products. The results from this brief follow-up study offer preliminary support for tideglusib as a treatment for both muscle and brain impairments in mdx mice, potentially improving cognitive function through enhanced vascular Aβ clearance."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • CTNNB1

Rosmarinic acid as a potential GSK3β inhibitor for autism spectrum disorder: insights from an integrative in silico study. (PubMed, In Silico Pharmacol) - "Molecular docking showed RA binds robustly to GSK3β's ATP-binding pocket (estimated affinity: 58.11 nM in SeeSAR scoring), compared to previously validated inhibitors such as Tideglusib (4077.20 nM in SeeSAR scoring) and Laduviglusib (93.26 nM in SeeSAR scoring)...Together, these findings provide convergent computational evidence that RA may directly interact with GSK3β, supporting further biochemical and cellular validation studies to assess its potential as a modulator of GSK3β-associated pathways relevant to ASD pathophysiology. The online version contains supplementary material available at 10.1007/s40203-026-00627-2."

Journal • Autism Spectrum Disorder • Genetic Disorders • CDK2

Combined application of a GSK3 inhibitor and injectable platelet rich fibrin with deproteinized bovine bone improves bone regeneration. (PubMed, Sci Rep) - No abstract available

Journal

Recent advances in drug repurposing for dentin repair. (PubMed, Arch Oral Biol) - "Leveraging drug repurposing for dentin repair underscores the significance of translating into dentistry knowledge gained from basic, pre-clinical and clinical research in other medical conditions, laying the groundwork for cost-effective therapeutic strategies and improved outcomes in regenerative dental medicine."

Journal • Review • Mood Disorders

Synthesis, Bioactivity and Molecular Modeling Studies on Benzimidazole Derivatives and Its Isosteres as Potent AChE/BChE and GSK3β Inhibitors for Alzheimer's Disease. (PubMed, Chem Biol Drug Des) - "The inhibition of GSK3β was assessed by measuring phosphorylated GSK3β (pGSK3β, Ser9) protein expression via Western Blot analysis under oxidative stress conditions. Among the tested compounds, 1l, 2b, 2j, and 3l significantly increased pGSK3β (Ser9) protein levels compared to cells treated with tideglusib, a known GSK3β inhibitor."

Journal • Alzheimer's Disease • CNS Disorders • Neuroblastoma • Oncology • Pain • Solid Tumor

Targeting the GSK-3β/mTOR axis: a novel pharmacological strategy for preeclampsia prevention and treatment. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Recent evidence identifies the deregulation of the glycogen synthase kinase-3β (GSK-3β) and mechanistic target of rapamycin (mTOR) signaling pathway as a primary pathogenic factor in impaired placentation...We combine molecular pathogenesis with computational docking analyses to assess therapeutic candidates, including metformin, statins, tideglusib, and the mTOR activator MHY1485, that specifically regulate GSK-3β/mTOR activity. Our findings indicate that drugs like atorvastatin and tideglusib demonstrate a robust binding affinity for GSK-3β, whereas MHY1485 interacts with a regulatory pocket in mTOR, hence reinforcing their mechanistic potential...We present the SWITCH Protocol, a precise preventive approach that integrates first-trimester biomarker screening with placenta-targeted medication. This study integrates structural insights, preclinical evidence, and translational trial design to establish GSK-3β/mTOR regulation as a fundamental pharmaceutical strategy for..."

Journal • Review • Gynecology • GSK3B

MECHANISMS OF NEURONAL DYSFUNCTION ASSOCIATED WITH PATHOGENIC TRUNCATED TAU (ADPD 2026) - "Some brain slices were treated with GSK-3 antagonists (Tideglusib) or HCN channel modulators (Zatebradine) prior to analysis. In association with increases in tau phosphorylation in Tau35 hippocampus, elevations in HCN1 and HCN3 channel protein levels and GSK-3 activity are evident... Tau-induced HCN channelopathy disrupts structural and functional aspects of synaptic integrity, contributing to network-wide deficits in neuronal connectivity. These findings suggest that selective targeting of HCN channels may offer a novel therapeutic strategy to mitigate synaptic dysfunction in tauopathies. It is now important to determine if GSK-3β overactivation in these mice alter the biophysical and biomolecular properties of voltage gated cationic channels."

Alzheimer's Disease • CNS Disorders • Dementia

Targeting Soluble VCAM1 and GSK3β Improves Cerebrovascular Function and Reduces Stroke Pathology in Diabetic Mice. (PubMed, Cells) - "In contrast, pharmacological inhibition of Akt with MK2206 activated Glycogen Synthase Kinase 3 beta (GSK3β) and increased MC degranulation without affecting HDC expression. Neutralizing VCAM1 with a monoclonal antibody reduced circulating sVCAM1 and histamine levels, and, together with the GSK3β inhibitor Tideglusib, stabilized MCs, normalized cerebral artery tone, and reduced post-MCAO infarct size and edema. These findings identify two distinct yet complementary mast cell pathways in T2D, highlight an immune-vascular interface that drives cerebrovascular dysfunction, and propose sVCAM1 blockade plus GSK3β inhibition as rational strategies to protect cerebral vascular function in the diabetic brain."

Journal • Preclinical • Cardiovascular • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • GSK3B • HDC • HRH2 • VCAM1

Hyperinsulinemia drives glomerular podocyte injury and albuminuria via a self-perpetuating GSK3β-IRS1 insulin desensitization circuit. (PubMed, Metabolism) - "In contrast, forced expression of a kinase-dead mutant of GSK3β or inhibition of GSK3β with a selective small-molecule inhibitor tideglusib abrogated inhibitory phosphorylation of IRS1S332, restored insulin sensitivity and protected podocytes...Collectively, hyperinsulinemia directly elicits albuminuria and renal impairment via a cascade of molecular events involving insulin receptor exhaustion, reduced insulin signaling, and GSK3β hyperactivity, which promotes IRS1 inhibition and thereby forms a self-amplifying GSK3β-IRS1 circuit of insulin desensitization and podocyte injury. Targeting GSK3β could disrupt this pathogenic loop and mitigate hyperinsulinemia-induced renal injury."

Journal • Metabolic Disorders • Nephrology • Renal Disease • GSK3B • IR

Tideglusib accelerates bone-tendon interface healing and improves mechanical strength in a rabbit rotator cuff tear model: an experimental study. (PubMed, J Orthop Surg Res) - "Local application of tideglusib positively enhances tendon-bone healing both biomechanically and histologically. Further studies are warranted to explore its potential clinical applications."

Journal • Preclinical

Apoptosis and motor deficits in SPG76 hereditary spastic paraplegia: calpain 2 inhibition as therapeutic strategy. (PubMed, Pharmacol Res) - "We found that the calpain inhibitors olesoxime and MDL28170, naringenin and the GSK3β inhibitor tideglusib were the most effective in increasing Akt activation and GSK3β inhibition and in rescuing apoptosis and cell death in SPG76 cells. Among these, olesoxime and MDL28170 reduced calpain activity, rescued apoptosis and locomotor deficits in vivo in a CalpB KO Drosophila model that replicates the SPG76 phenotype."

Journal • CNS Disorders • Genetic Disorders • CAPN1 • CAPN2

Drug Development. (PubMed, Alzheimers Dement) - "This design strategy could be used for the lead optimization of GSK-3β Inhibitors and focusing attention on the exciting therapy could thus reap considerable clinical and economic rewards."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

Tideglusib-loaded chitosan-incorporated bacterial cellulose hydrogel for enhanced palatal wound healing. (PubMed, Int J Biol Macromol) - "Pairwise comparisons demonstrated significant differences between the baseline and Td + Hydrogel groups only. Topical use of chitosan incorporated BC-based hydrogel loaded with Td suggested a beneficial impact on the healing of palatal mucosal wounds in rats."

Journal • Pain

Cardiac Involvement in Myotonic Dystrophy Type 1: Mechanisms, Clinical Perspectives, and Emerging Therapeutic Strategies. (PubMed, Int J Mol Sci) - "ASOs aim to reduce toxic RNA accumulation, CRISPR-based approaches aim to excise or correct the expanded CTG repeats, and repurposed small-molecule drugs, such as vorinostat, tideglusib, and metformin, could serve as potential therapeutic agents for DM1 patients with cardiac complications. More research and well-designed clinical trials are urgently needed to translate these promising strategies into effective treatments for DM1-associated cardiac disease. Here, we discuss the current knowledge in DM1 cardiac pathology and preclinical models as well as the benefits and pitfalls of the available therapeutic approaches."

Journal • Review • Cardiovascular • Genetic Disorders • Heart Failure • Muscular Dystrophy • Myotonic Dystrophy • Respiratory Diseases

Targeted strategy by curcumin and tideglusib biomimetic nano-systems alleviates oxidative stress and inflammation under ischemic stroke. (PubMed, Drug Deliv) - "Additionally, Cur@PLTM and Tid@PLTM synergistically scavenged reactive oxygen species (ROS) and promoted the secretion of neuroprotective cytokines via redox and cellular regulatory mechanisms to mitigate ischemia/reperfusion (I/R) injury. Overall, this platelet membrane-biomimetic nanosystem offers a prospective strategy for targeted brain delivery and combined treatment through antioxidative and anti-inflammatory approaches against ischemic stroke."

Journal • Cardiovascular • Inflammation • Ischemic stroke • Reperfusion Injury

Elevated Levels of Active GSK3β in the Blood of Patients with Myotonic Dystrophy Type 1 Correlate with Muscle Weakness. (PubMed, Int J Mol Sci) - "Previously, we described that the small-molecule inhibitor of GSK3β, tideglusib (TG), reduces DM1 pathology in DM1 cell and mouse models by correcting the GSK3β-CUGBP1 pathway, decreasing the mutant CUG-containing RNA...Thrombospondin and TGFβ, linked to the TG-GSK3β pathway in DM1, are also elevated in the DM1 patients' blood. These findings show that the blood levels of active GSK3β might be developed as a potential noninvasive biomarker of muscle weakness in DM1."

Journal • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy • GSK3B • TGFB1

The synergistic effect of low-intensity focused ultrasound and tideglusib on odontogenic differentiation of human dental pulp stem cells. (PubMed, Clin Oral Investig) - "This pharmacomechanical approach offers a minimally invasive, biologically driven strategy for regenerative endodontic therapy, with strong translational potential in managing reversible pulpitis and promoting dentine repair."

Journal • Dental Disorders • BCL2L1 • BMP2 • CASP3 • RUNX2

Computational identification of phytochemicals as glycogen synthase kinase 3 beta (GSK3β) inhibitors for therapeutic applications in chronic diseases. (PubMed, Sci Rep) - "ADMET profiling shortlisted 49 compounds, with uzarigenin, jatrophone, chrysin, and podolide exhibiting superior binding affinities compared to Tideglusib (-8.53 kcal/mol)...KEGG pathway analysis highlighted the role of GSK-3β inhibitors in Alzheimer's disease, Wnt signaling, and cancer pathways. This study identifies phytochemicals with potential therapeutic applications for neurodegenerative, cancer, and metabolic diseases, warranting further experimental validation."

Journal • Alzheimer's Disease • CNS Disorders • Diabetes • Metabolic Disorders • Oncology