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Name: Tideglusib
Synonyms: NP031112, Nypta® , Zentylor™ , Glycogen synthase kinase 3 inhibitor, NP12
Chemical Name: 4-Benzyl-2-(naphthalen-1-yl)-1,2,4-thiadiazolidine-3,5-dione
Therapy Type: Small Molecule (timeline)
Target Type: Tau (timeline)
Condition(s): Alzheimer's Disease, Progressive Supranuclear Palsy
U.S. FDA Status: Alzheimer's Disease (Discontinued), Progressive Supranuclear Palsy (Discontinued)
Company: Zeltia Group


Tideglusib is an orally available, small-molecule drug of the thiadiazolidinone class. It acts as an inhibitor of glycogen synthase kinase 3 (GSK3-β), a widely studied tau kinase. The rationale for its use is that inhibiting GSK3-β will counteract tau hyperphosphorylation, which is thought be a step in the cellular pathogenesis that leads to Alzheimer's disease and other neurodegenerative diseases marked by neurofibrillary tau pathology. Tideglusib was being developed for the treatment of Alzheimer's and the tauopathy progressive supranuclear palsy (PSP) as part of a drug-discovery program based on marine-derived GSK3-β inhibitors. In preclinical studies, tideglusib was reported to reduce a range of disease outcomes, including tau phosphorylation, amyloid deposition, neuron loss, and gliosis in mouse entorhinal cortex and hippocampus, and to reverse a spatial memory deficit in transgenic mice. Neuroprotective, anti-inflammatory, and neurogenesis-inducing effects of tideglusib have been reported in animal models, as well (e.g. Sereno et al., 2009Morales-Garcia et al., 2012, Wang et al., 2016).


A Phase 2a, escalating-dose trial compared four escalating doses ranging from 400–1,000 mg/day to placebo in 30 patients with mild to moderate AD. Conducted at three sites in Germany, this five-month trial evaluated safety and effects on cognition and mood. It reported good tolerability except for a transient increase in serum transaminase levels. It also reported trends for a cognitive benefit on the MMSE screen and ADAS-Cog test battery (see del Ser et al., 2013).

A subsequent six-month, Phase 2b trial in 306 patients with mild to moderate AD ran in 55 centers in Spain, Germany, and other European countries. It compared 1,000 mg taken once daily, 1,000 mg taken every other day, and 500 mg once daily against placebo, and measured cognition with the ADAS-Cog as primary outcome. Called ARGO, the trial started in April 2011 and ended in July 2012. This trial was reported to have missed its primary endpoint and some secondary endpoints (see El Economista articlePharmaTimes article); subsequently, results were formally published (Lovestone et al., 2015).

In 2009, tideglusib received FDA and EMA orphan drug status, and in 2010 received FDA fast-track status for progressive supranuclear palsy, a tauopathy considered suitable to test treatments targeting this protein. In 2009, Noscira started a one-year study in 146 patients with PSP. Called TAUROS, this multicenter European trial compared 600 and 800 mg of tideglusib taken once a day to placebo, measuring change in the Progressive Supranuclear Palsy Rating Scale of Golbe as primary outcome. Tideglusib reportedly showed a signal toward reduced brain atrophy in a subgroup analysis (see company press release, Hoglinger et al., 2014); however, this trial, too, was negative on the primary outcome (Tolosa et al., 2014)

In 2016, clinial trials started evaluating tideglusib for the treatment of congenital As of 2019, tideglusib was in clinical trials for myotonic dystrophy. For all cinical trials of this drug, see

Noscira was set up in 2000 as a subsidiary of the Spanish Zeltia Group, under the name Neuropharma. It was renamed Noscira in 2008, and its impending liquidation was announced in December 2012 (see Reuters story).

Last Updated: 03 Jun 2019


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Paper Citations

  1. . Treatment of Alzheimer's Disease with the GSK-3 Inhibitor Tideglusib: A Pilot Study. J Alzheimers Dis. 2012 Aug 30; PubMed.
  2. . A phase II trial of tideglusib in Alzheimer's disease. J Alzheimers Dis. 2015;45(1):75-88. PubMed.
  3. . Tideglusib reduces progression of brain atrophy in progressive supranuclear palsy in a randomized trial. Mov Disord. 2014 Apr;29(4):479-87. Epub 2014 Jan 31 PubMed.
  4. . A novel GSK-3beta inhibitor reduces Alzheimer's pathology and rescues neuronal loss in vivo. Neurobiol Dis. 2009 Sep;35(3):359-67. PubMed.
  5. . Glycogen synthase kinase 3 inhibition promotes adult hippocampal neurogenesis in vitro and in vivo. ACS Chem Neurosci. 2012 Nov 21;3(11):963-71. PubMed.
  6. . Tideglusib, a chemical inhibitor of GSK3β, attenuates hypoxic-ischemic brain injury in neonatal mice. Biochim Biophys Acta. 2016 Oct;1860(10):2076-85. Epub 2016 Jul 1 PubMed.

External Citations

  1. El Economista article
  2. PharmaTimes article
  3. company press release
  4. (Tolosa et al., 2014)
  6. Reuters story

Further Reading


  1. . Evidence for irreversible inhibition of glycogen synthase kinase-3β by tideglusib. J Biol Chem. 2012 Jan 6;287(2):893-904. PubMed.
  2. . Glycogen synthase kinase 3 inhibitors in the next horizon for Alzheimer's disease treatment. Int J Alzheimers Dis. 2011;2011:280502. PubMed.
  3. . A phase II trial of tideglusib in Alzheimer's disease. J Alzheimers Dis. 2015;45(1):75-88. PubMed.