Trial reportBritish journal of pharmacology2017
Selection and early clinical evaluation of the brain-penetrant 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor UE2343 (Xanamem™).
Trial report in British journal of pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 28 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase I Double-Blind, Randomised, Placebo-Controlled, Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of UE2343 in Healthy Subjects
XanADu: A Phase II, Double-Blind, 12-Week, Randomised, Placebo-Controlled Study to Assess the Safety, Tolerability and Efficacy of Xanamem™ in Subjects With Mild Dementia Due to Alzheimer's Disease (AD)
XanaHES: A Phase I, Single Blinded, Central Reader Blinded, Placebo-Controlled, Dose Escalation Study of Xanamem™ to Assess Safety and Tolerability in Healthy Elderly Subjects
XanaMIA-DR a Double-Blind, Placebo-Controlled, Dose Ranging Study to Assess the Efficacy, Pharmacodynamics and Safety of Xanamem® in Healthy Elderly Volunteers
Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Role of 11β-Hydroxysteroid Dehydrogenase and Mineralocorticoid Receptor on Alzheimer's Disease Onset: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- Plasma pTau181 Predicts Clinical Progression in a Phase 2 Randomized Controlled Trial of the 11β-HSD1 Inhibitor Xanamem® for Mild Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2024Trial
- Safety, tolerability, pharmacodynamics and pharmacokinetics following once-daily doses of BI 187004, an inhibitor of 11 beta-hydroxysteroid dehydrogenase-1, over 28 days in patients with type 2 diabetes mellitus and overweight or obesity.Diabetes, obesity & metabolism · 2023Trial
- Selection and early clinical evaluation of the brain-penetrant 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor UE2343 (Xanamem™).British journal of pharmacology · 2017Trial
- Stress, stress systems, and Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Clinical Pharmacology and Approach to Dose Selection of Emestedastat, a Novel Tissue Cortisol Synthesis Inhibitor for the Treatment of Central Nervous System Disease.Clinical pharmacology in drug development · 2025Review
- Brain 11β-Hydroxysteroid Dehydrogenase Type 1 Occupancy by Xanamem™ Assessed by PET in Alzheimer's Disease and Cognitively Normal Individuals.Journal of Alzheimer's disease : JAD · 2024Article
- The Importance of PET Imaging to Understanding Whole-Body Cortisol Metabolism in Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2024Review
- Article
- Contribution of local regeneration of glucocorticoids to tissue steroid pools.The Journal of endocrinology · 2023Article
- Age-related Changes in the Adrenal Cortex: Insights and Implications.Journal of the Endocrine Society · 2023Review
- Article
- Weak Noncovalent Interactions in Three Closely Related Adamantane-Linked 1,2,4-TriazoleMolecules (Basel, Switzerland) · 2022Article
- Non-invasive in vivo assessment of 11β-hydroxysteroid dehydrogenase type 1 activity byScientific reports · 2022Article
- Effect of Glucocorticoid and 11β-Hydroxysteroid-Dehydrogenase Type 1 (11β-HSD1) in Neurological and Psychiatric Disorders.The international journal of neuropsychopharmacology · 2022Article
- The Development of Pharmacological Therapies for Alzheimer's Disease.Neurology and therapy · 2021Review
- Inhibition of 11β-HSD1 Ameliorates Cognition and Molecular Detrimental Changes after Chronic Mild Stress in SAMP8 Mice.Pharmaceuticals (Basel, Switzerland) · 2021Article
- The ratio of ursodeoxycholyltaurine to 7-oxolithocholyltaurine serves as a biomarker of decreased 11β-hydroxysteroid dehydrogenase 1 activity in mouse.British journal of pharmacology · 2021Article
- 11β-hydroxysteroid dehydrogenases: A growing multi-tasking family.Molecular and cellular endocrinology · 2021Review
- Cognitive performance in idiopathic intracranial hypertension and relevance of intracranial pressure.Brain communications · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
background and purposeReducing glucocorticoid exposure in the brain via intracellular inhibition of the cortisol-regenerating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) has emerged as a therapeutic strategy to treat cognitive impairment in early Alzheimer's disease (AD). We sought to discover novel, brain-penetrant 11β-HSD1 inhibitors as potential medicines for the treatment of AD. EXPERIMENTAL APPROACH: Medicinal chemistry optimization of a series of amido-thiophene analogues was performed to identify potent and selective 11β-HSD1 inhibitors with optimized oral pharmacokinetics able to access the brain. Single and multiple ascending dose studies were conducted in healthy human subjects to determine the safety, pharmacokinetic and pharmacodynamic characteristics of the candidate compound.
resultsUE2343 was identified as a potent, orally bioavailable, brain-penetrant 11β-HSD1 inhibitor and selected for clinical studies. No major safety issues occurred in human subjects. Plasma adrenocorticotropic hormone was elevated (a marker of systemic enzyme inhibition) at doses of 10 mg and above, but plasma cortisol levels were unchanged. Following multiple doses of UE2343, plasma levels were approximately dose proportional and the terminal t CONCLUSIONS AND IMPLICATIONS: UE2343 is safe, well tolerated and reaches the brain at concentrations predicted to inhibit 11β-HSD1. UE2343 is therefore a suitable candidate to test the hypothesis that 11β-HSD1 inhibition in brain improves memory in patients with AD.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.