- |||||||||| sarizotan (EMD128130) / Newron, Rhopressa (netarsudil) / Alcon
Journal: Repurposing Drugs for Inhibition against ALDH2 via a 2D/3D Ligand-Based Similarity Search and Molecular Simulation. (Pubmed Central) - Nov 18, 2023
The electrostatic attraction with positively charged compounds, however, yielded very strong binding results with ALDH2. These findings reveal a deficiency in the modeling of electrostatic interactions (in particular, between charged moieties) in the virtual screening via the 2D/3D similarity search and molecular docking with the Vina scoring system.
- |||||||||| sarizotan (EMD128130) / Newron
Journal: Structure-based virtual screening and molecular docking approaches to identify potential inhibitors against KIF2C to combat glioma. (Pubmed Central) - Nov 9, 2023
The docking results were examined using the Glide gscore, and the best binding compounds (Rimacalib and Sarizotan) were chosen to test their stability with KIF2C protein through molecular dynamics (MD) simulation...The MM/GBSA binding free energies showed a considerable energy contribution in the binding of hits with the KIF2C. Collectively, these findings strongly suggest the potential of the lead compounds to inhibit the biological function of KIF2C, emphasizing the need for further investigation in this area.Communicated by Ramaswamy H. Sarma.
- |||||||||| sarizotan (EMD128130) / Newron
Journal: Tandem InCl-Promoted Hydroperoxide Rearrangements and Nucleophilic Additions: A Straightforward Entry to Benzoxacycles. (Pubmed Central) - Jul 10, 2023
This article describes the tandem process between a Hock or Criegee oxidative cleavage and a nucleophilic addition onto the oxocarbenium species (in particular a Hosomi-Sakurai-type allylation), under InCl catalysis. It was applied to the synthesis of 2-substituted benzoxacycles (chromanes and benzoxepanes), including a synthesis of the 2-(aminomethyl)chromane part of sarizotan, and a total synthesis of erythrococcamide B.
- |||||||||| Review, Journal: 5-HT agonists for levodopa-induced dyskinesia in Parkinson's disease. (Pubmed Central) - May 4, 2023
Clinical trials testing 5-HT agonists have yielded inconsistent results in alleviating dyskinesia, especially that the antidyskinetic benefit observed was often accompanied by an adverse effect on motor function. In this article, we summarize and analyze the various clinical trials performed with 5-HT agonists in PD patients with dyskinesia and offer perspectives on the future of this class of agents in PD.
- |||||||||| sarizotan (EMD128130) / Newron
Clinical, Review, Journal: Current Therapies in Clinical Trials of Parkinson's Disease: A 2021 Update. (Pubmed Central) - Aug 29, 2021
In 1970, the United States Food and Drug Administration approved the drug levodopa as a dopamine replacement to manage PD motor symptoms; levodopa-carbidopa combination became commercialized in 1975...The three phase-III trials use embryonic dopamine cell implant, 5-HT receptor agonist (sarizotan), and adenosine A receptor antagonist (caffeine)...Additionally, we discuss the most potent drug or therapy among these trials. By systematically updating the current trial status and analyzing the therapeutic strategies, we hope this review can provide new ideas and insights for PD therapy development.
- |||||||||| sarizotan (EMD128130) / Newron
Trial completion date, Trial termination: STARS: Evaluation of the Efficacy, Safety, and Tolerability of Sarizotan in Rett Syndrome With Respiratory Symptoms (clinicaltrials.gov) - Nov 9, 2020
P2/3, N=129, Terminated,
By systematically updating the current trial status and analyzing the therapeutic strategies, we hope this review can provide new ideas and insights for PD therapy development. Trial completion date: Apr 2019 --> Jul 2020 | Active, not recruiting --> Terminated; The study did not demonstrate evidence of efficacy on the primary or secondary efficacy variables
- |||||||||| sarizotan (EMD128130) / Newron, Cognex (tacrine) / Shionogi
Preclinical, Journal: Non-dopaminergic Alterations in Depression-Like FSL Rats in Experimental Parkinsonism and L-DOPA Responses. (Pubmed Central) - Apr 9, 2020
FSL rats showed a potentiated tremorgenic response to tacrine, a cholinesterase inhibitor used experimentally to induce 6 Hz resting tremor reminiscent of parkinsonian tremor...However, following chronic treatment with L-DOPA, FRL rats developed sensitization of turning and abnormal involuntary movements (AIMs); these effects were counteracted by the anti-dyskinetic 5-HT agonist/D partial agonist sarizotan...The marked behavioral difference between the FRL and FSL rats was paralleled with the striatal expression of the established marker, c-fos, but also the GABAergic transporter (vGAT), and a hitherto unknown marker, tamalin, that is known to regulate mGluR5 receptor function and postsynaptic organization. This study demonstrates that behavioral and transcriptional responses of non-dopaminergic systems to experimental parkinsonism and L-DOPA are modified in a genetic rat model of depression.
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