- |||||||||| Nypta (tideglusib) / ASD Therap
Review, Journal: GSK-3: An "Ace" Among Kinases. (Pubmed Central) - Nov 13, 2024 Significant findings of miRNA regulation by GSK-3 exemplify the underpinnings of kinase-mediated transcriptional regulation in cancers. The review provides evidence on the role of GSK-3 as a possible master regulator of proteins and noncoding RNA, thereby implicating the fate of a cell.
- |||||||||| Nypta (tideglusib) / ASD Therap
Journal: The Effect of Tideglusib Application on Type 1 and Type 3 Collagen Expressions by Human Dental-Pulp Derived Stem Cells: A Preliminary Study. (Pubmed Central) - Sep 30, 2024 inhibition in patients with arrhythmogenic cardiomyopathy, this report aims to review the advantages and disadvantages of this strategy. The fact that Wnt signaling pathway activation obtained by Tideglusib application on DPSCs confirmed by the finding in the increase of Axin-2 at short and long-term evaluation periods which is resulted in the increase in the type 1 collagen expression at 24 h and decrease at 1 week together with the decrease in type 3 collagen expression at 1 week warrants further studies to evaluate the effect of Tideglusib on extracellular matrix expression.
- |||||||||| Nypta (tideglusib) / ASD Therap, Amnolake (tamibarotene) / Syros
Journal: Cocktail Cell-Reprogrammed Hydrogel Microspheres Achieving Scarless Hair Follicle Regeneration. (Pubmed Central) - Jan 16, 2024 In vitro and in vivo studies show that AHFS can regulate fibroblast fate, induce fibroblast-to-DPC reprogramming by activating the PI3K/AKT pathway, finally promoting wound healing and in situ HF regeneration while inhibiting scar formation in a two-pronged translational approach. In conclusion, AHFS provides a new and effective strategy for functional repair of skin wounds.
- |||||||||| Nypta (tideglusib) / ASD Therap
Journal: Tideglusib-incorporated nanofibrous scaffolds potently induce odontogenic differentiation. (Pubmed Central) - Aug 8, 2023 In contrast to current pulp capping material driving dentin repair, the sophisticated, polymeric scaffold systems with soluble and insoluble spatiotemporal cues described here can direct stem cell differentiation and dentin regeneration. Hence, bioactive small molecule-incorporated nanofibrous scaffold suggests an innovative clinical tool for dentin tissue engineering.
- |||||||||| Nypta (tideglusib) / ASD Therap
Journal: Therapeutic Targeting of the GSK3?-CUGBP1 Pathway in Myotonic Dystrophy. (Pubmed Central) - Jul 18, 2023 We have previously described the benefits of the correction of the GSK3?-CUGBP1 pathway in DM1 mice (HSA model) expressing 250 CUG repeats using the GSK3 inhibitor tideglusib (TG)...Using a mouse model with dysregulated CUGBP1, which mimics alterations in DM1, we showed that the dysregulated CUGBP1 contributes to the toxicity of expanded CUG repeats by changing gene expression and causing CNS abnormalities. These data show the critical role of the GSK3?-CUGBP1 pathway in DM1 muscle and in CNS pathologies, suggesting the benefits of GSK3 inhibitors in patients with different forms of DM1.
- |||||||||| Nypta (tideglusib) / ASD Therap
Trial completion date, Trial primary completion date: TIDALS: Tideglusib for the Treatment of Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - Jun 2, 2023 P2, N=98, Not yet recruiting, degraders as potential therapeutic agents. Trial completion date: Mar 2024 --> Mar 2026 | Trial primary completion date: Dec 2023 --> Dec 2025
- |||||||||| Nypta (tideglusib) / ASD Therap
Enrollment status, Enrollment change, Trial completion date, Trial primary completion date: REACH CDM X: Safety and Efficacy of Tideglusib in Congenital or Childhood Onset Myotonic Dystrophy (clinicaltrials.gov) - May 24, 2023 P2/3, N=76, Recruiting, Trial completion date: Mar 2024 --> Mar 2026 | Trial primary completion date: Dec 2023 --> Dec 2025 Enrolling by invitation --> Recruiting | N=56 --> 76 | Trial completion date: Mar 2023 --> Mar 2025 | Trial primary completion date: Mar 2023 --> Mar 2025
- |||||||||| Review, Journal: The myotonic dystrophy type 1 drug development pipeline: 2022 edition. (Pubmed Central) - Mar 2, 2023
Three interventional first-in-human clinical trials got underway with distinct drug classes, namely AOC 1001 and DYNE-101 nucleic acid-based therapies, and the small molecule pitolisant, which joins the race toward market authorization with other repurposed drugs, including tideglusib, metformin, or mexiletine, already in clinical evaluation. Furthermore, newly disclosed promising preclinical data for several additional nucleic-acid therapeutic candidates and a CRISPR-based approach, as well as the advent into the pipeline of novel therapeutic programs, increase the plausibility of success in the demanding task of providing valid treatments to patients with DM1.
- |||||||||| Nypta (tideglusib) / ASD Therap
Enrollment closed, Trial primary completion date: REACH CDM: Efficacy and Safety of Tideglusib in Congenital Myotonic Dystrophy (clinicaltrials.gov) - Feb 24, 2023 P2/3, N=56, Active, not recruiting, Furthermore, newly disclosed promising preclinical data for several additional nucleic-acid therapeutic candidates and a CRISPR-based approach, as well as the advent into the pipeline of novel therapeutic programs, increase the plausibility of success in the demanding task of providing valid treatments to patients with DM1. Recruiting --> Active, not recruiting | Trial primary completion date: Jan 2023 --> Apr 2023
- |||||||||| Nypta (tideglusib) / ASD Therap, LY2090314 / Eli Lilly
Journal: Molecular docking study of GSK-3β interaction with nomilin, kihadanin B, and related limonoids and triterpenes with a furyl-δ-lactone core. (Pubmed Central) - Sep 20, 2022 Numerous inhibitors of GSK-3β have been discovered but thus far only a few have reached clinical trials and only one drug, tideglusib (1), has been registered...The formation of GSK-3β-binding complexes for those natural products was compared to reference GSK-3β ATP-competitive inhibitors LY2090314 (3) and AR-A014418 (2)...Compound structure-binding relationships are discussed. The study should help the discovery of novel natural products targeting GSK-3β.
- |||||||||| Nypta (tideglusib) / ASD Therap
Journal: Tideglusib promotes wound healing in aged skin by activating PI3K/Akt pathway. (Pubmed Central) - Jun 23, 2022 The decreased expression of EGFR in epidermis with age resulted in decreased activity of the PI3K/Akt pathway and limited EGF efficacy. Tideglusib could assist wound healing in aged rats via activating PI3K/Akt pathway, which may be considered as an ingredient for medical and cosmetics use.
- |||||||||| Nypta (tideglusib) / ASD Therap, benzesulfonate (PF-562271) / Pfizer
Journal: Focal adhesion kinase inhibitors prevent osteoblast mineralization in part due to suppression of Akt-mediated stabilization of osterix. (Pubmed Central) - May 29, 2022 In this study we evaluated whether use of the FAK TKI PF-562,271 affected the differentiation of pre-osteoblasts, or activity of mature differentiated osteoblasts...As we observed that FAK TKI also resulted in suppression of Akt, which is known to alter osterix protein stability downstream of RUNX2, we examined protein levels by western blot and found a dose-dependent decrease in osterix in FAK TKI treated differentiated MC3T3-E1 cells which is likely responsible for the reduced mineralization observed. Taken together our results suggest that use of FAK TKIs as therapeutics in the bone metastatic setting may block new bone formation as an off-target effect and thereby exacerbate the defective bone regulation that is characteristic of the bone metastatic environment.
- |||||||||| diazepinomicin (AMO-01) / AMO Pharma
Preclinical, Journal: Secondary Metabolites of Actinomycetales as Potent Quorum Sensing Inhibitors Targeting Gram-Positive Pathogens: In Vitro and In Silico Study. (Pubmed Central) - Mar 25, 2022 The results indicated that four compounds, Phenalinolactones A-D, BU-4664LMe, 4,5-dehydrogeldamycin, and Questinomycin A, potentially inhibit the agr quorum sensing system and hemolytic activity of S. aureus...Further, in silico molecular docking studies were performed which provided closer insights into the mode of action of these compounds and proposed that the inhibitory activity of these compounds could be attributed to their potential ability to bind to the ATP-active site of S. aureus AgrA. Taken together, our study highlights the potential of actinomycetales secondary metabolites with diverse structures as anti-virulence quorum sensing inhibitors.
- |||||||||| Nypta (tideglusib) / ASD Therap, LY2090314 / Eli Lilly, elraglusib (9-ING-41) / Actuate Therap
Journal: Proposed hypothesis of GSK-3 β inhibition for stimulating Wnt/β-catenin signaling pathway which triggers liver regeneration process. (Pubmed Central) - Mar 11, 2022 Various signaling pathways for liver regeneration are HO-1/BER pathway, Tweak/Fn14 signaling pathway, Hippo pathway, Wnt/beta-catenin pathway, Hedgehog signaling pathway, bile acids repairing pathway, serotonin (5HT) pathway, estrogen pathway, thyrotropin-releasing hormone (TRH) pathway, insulin repairing pathway, etc. The in vitro scientific literature revealed that numerous GSK-3 β inhibitors (LY 2090314, AR-A014418, Tideglusib, Solasodine, CHIR99021, 9-ING-41, SB-216763) play an important role in stimulating the liver regeneration process. Similarly, from the above discussion, the direction is highlighted to emphasize the proposed molecular Wnt/β-catenin signaling pathway which is associated with GSK-3 β inhibition for the induction of the repairing and regeneration process.
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