ArticleMolecular neurobiology2022
Non-clinical Pharmacology of YTX-7739: a Clinical Stage Stearoyl-CoA Desaturase Inhibitor Being Developed for Parkinson's Disease.
Article in Molecular neurobiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 31 citations in OpenAlex.
- Condensate-driven triglyceride reduction links α-synuclein to mitochondrial dysfunction.EMBO reports · 2026Article
- Elevation of Stearoyl-Coenzyme A Desaturase and Monounsaturated Fatty Acids in Parkinson's Disease Serum.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- α-Synuclein as a molecular link between Parkinson's disease and chronic kidney disease: insights into the kidney-brain axis.Metabolic brain disease · 2026Review
- Mapping the developmental path for Parkinson's disease therapeutics.NPJ Parkinson's disease · 2025Article
- Parkinson disease is a fatty acidopathy.Nature reviews. Neurology · 2025Review
- Dysregulation of Monounsaturated Fatty Acids is Related to α-Synuclein in Multiple System Atrophy.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Targeting SCD triggers lipotoxicity of cancer cells and enhances anti-tumor immunity in breast cancer brain metastasis mouse models.Communications biology · 2025Article
- Interactions of alpha-synuclein with membranes in Parkinson's disease: Mechanisms and therapeutic strategies.Neurobiology of disease · 2024Review
- A Multimodal Drug-Diet-Immunotherapy Combination Restrains Melanoma Progression and Metastasis.Cancer research · 2024Article
- Recent Advances in Clinical Trials in Multiple System Atrophy.Current neurology and neuroscience reports · 2024Review
- Relationships between erythrocyte membrane mono- and poly- unsaturated fatty acid composition and clinical/cognitive indices in antipsychotic-free schizophrenia patients.Frontiers in psychiatry · 2024Article
- Association of serum oleic acid level with depression in American adults: a cross-sectional study.BMC psychiatry · 2023Article
- Prosaposin maintains lipid homeostasis in dopamine neurons and counteracts experimental parkinsonism in rodents.Nature communications · 2023Article
- Inhibition of Protein Aggregation and Endoplasmic Reticulum Stress as a Targeted Therapy for α-Synucleinopathy.Pharmaceutics · 2023Review
- Targeting de novo lipid synthesis induces lipotoxicity and impairs DNA damage repair in glioblastoma mouse models.Science translational medicine · 2023Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stearoyl-CoA desaturase (SCD) is a potential therapeutic target for Parkinson's and related neurodegenerative diseases. SCD inhibition ameliorates neuronal toxicity caused by aberrant α-synuclein, a lipid-binding protein implicated in Parkinson's disease. Its inhibition depletes monounsaturated fatty acids, which may modulate α-synuclein conformations and membrane interactions. Herein, we characterize the pharmacokinetic and pharmacodynamic properties of YTX-7739, a clinical-stage SCD inhibitor. Administration of YTX-7739 to rats and monkeys for 15 days caused a dose-dependent increase in YTX-7739 concentrations that were well-tolerated and associated with concentration-dependent reductions in the fatty acid desaturation index (FADI), the ratio of monounsaturated to saturated fatty acids. An approximate 50% maximal reduction in the carbon-16 desaturation index was observed in the brain, with comparable responses in the plasma and skin. A study with a diet supplemented in SCD products indicates that changes in brain C16 desaturation were due to local SCD inhibition, rather than to changes in systemic fatty acids that reach the brain. Assessment of pharmacodynamic response onset and reversibility kinetics indicated that approximately 7 days of dosing were required to achieve maximal responses, which persisted for at least 2 days after cessation of dosing. YTX-7739 thus achieved sufficient concentrations in the brain to inhibit SCD and produce pharmacodynamic responses that were well-tolerated in rats and monkeys. These results provide a framework for evaluating YTX-7739 pharmacology clinically as a disease-modifying therapy to treat synucleinopathies.
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