ArticleBMC endocrine disorders2018
ATR-101, a selective ACAT1 inhibitor, decreases ACTH-stimulated cortisol concentrations in dogs with naturally occurring Cushing's syndrome.
Article in BMC endocrine disorders, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- A Phase 2, Multicenter Study of Nevanimibe for the Treatment of Congenital Adrenal Hyperplasia.The Journal of clinical endocrinology and metabolism · 2020Trial
- Pharmacologic Alteration of Meibum Lipid Composition Alleviates Dry Eye Phenotype in Awat2-/- Mice.Investigative ophthalmology & visual science · 2026Article
- Effectiveness of Medical Treatment on Survivability in Canine Cushing's Syndrome: A Systematic Review and Meta-Analysis.Animals : an open access journal from MDPI · 2025Article
- The structure of phosphatidylinositol remodeling MBOAT7 reveals its catalytic mechanism and enables inhibitor identification.Nature communications · 2023Article
- YM750, an ACAT Inhibitor, Acts on Adrenocortical Cells to Inhibit Aldosterone Secretion Due to Depolarization.International journal of molecular sciences · 2022Article
- High expression of Sterol-O-Acyl transferase 1 (SOAT1), an enzyme involved in cholesterol metabolism, is associated with earlier biochemical recurrence in high risk prostate cancer.Prostate cancer and prostatic diseases · 2022Article
- De novo labeling and trafficking of individual lipid species in live cells.Molecular metabolism · 2022Article
- Novel treatments for congenital adrenal hyperplasia.Reviews in endocrine & metabolic disorders · 2022Review
- Synthesis and Evaluation ofACS medicinal chemistry letters · 2020Article
- Medical Treatment of Cushing's Disease: An Overview of the Current and Recent Clinical Trials.Frontiers in endocrinology · 2020Review
- Cushing's Disease.Journal of clinical medicine · 2019Review
- New strategies for applying targeted therapies to adrenocortical carcinoma.Current opinion in endocrine and metabolic research · 2019Article
- Adrenocortical carcinoma - towards genomics guided clinical care.Nature reviews. Endocrinology · 2019Review
- Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCushing's syndrome in humans shares many similarities with its counterpart in dogs in terms of etiology (pituitary versus adrenal causes), clinical signs, and pathophysiologic sequelae. In both species, treatment of pituitary- and adrenal-dependent disease is met with limitations. ATR-101, a selective inhibitor of ACAT1 (acyl coenzyme A:cholesterol acyltransferase 1), is a novel small molecule therapeutic currently in clinical development for the treatment of adrenocortical carcinoma, congenital adrenal hyperplasia, and Cushing's syndrome in humans. Previous studies in healthy dogs have shown that ATR-101 treatment led to rapid, dose-dependent decreases in adrenocorticotropic hormone (ACTH) stimulated cortisol levels. The purpose of this clinical study was to investigate the effects of ATR-101 in dogs with Cushing's syndrome.
methodsATR-101 pharmacokinetics and activity were assessed in 10 dogs with naturally-occurring Cushing's syndrome, including 7 dogs with pituitary-dependent disease and 3 dogs with adrenal-dependent disease. ATR-101 was administered at 3 mg/kg PO once daily for one week, followed by 30 mg/kg PO once daily for one (n = 4) or three (n = 6) weeks. Clinical, biochemical, adrenal hormonal, and pharmacokinetic data were obtained weekly for study duration.
resultsATR-101 exposure increased with increasing dose. ACTH-stimulated cortisol concentrations, the primary endpoint for the study, were significantly decreased with responders (9 of 10 dogs) experiencing a mean ± standard deviation reduction in cortisol levels of 50 ± 17% at study completion. Decreases in pre-ACTH-stimulated cortisol concentrations were observed in some dogs although overall changes in pre-ACTH cortisol concentrations were not significant. The compound was well-tolerated and no serious drug-related adverse effects were reported.
conclusionsThis study highlights the potential utility of naturally occurring canine Cushing's syndrome as a model for human disease and provides proof of concept for ATR-101 as a novel agent for the treatment of endocrine disorders like Cushing's syndrome in humans.
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