ArticleACS medicinal chemistry letters2026
Crystal Structure of the Sigma‑2 Receptor Complexed with Investigational Drug Zervimesine (CT1812).
Article in ACS medicinal chemistry letters, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Not yet cited in PubMed.
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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 Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 2 Study to Evaluate the Safety and Efficacy of CT1812 in Subjects With Mild to Moderate Alzheimer's Disease.
A Randomized, Double-blind, Placebo-controlled, Phase 2, 6-month Study to Evaluate the Safety, Tolerability and Exploratory Efficacy of CT1812 in Subjects With Mild to Moderate Dementia With Lewy Bodies
A Randomized, Double-Masked, Placebo-Controlled, Parallel-Group, Phase 2 Study to Evaluate the Efficacy and Safety of Oral CT1812 in Participants With Geographic Atrophy (GA) Secondary to Dry Age-Related Macular Degeneration (AMD).
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Authors and funding
10 authors.
Funding
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Abstract
The investigational drug zervimesine (CT1812) is an allosteric small molecule modulator of the sigma-2 receptor (S2R), known as transmembrane protein 97 (TMEM97), currently in clinical development for Alzheimer's disease and dementia with Lewy bodies. In Phase 2 trials, consistent favorable trends across outcome measures were observed for Alzheimer's disease (NCT03507790), dementia with Lewy Bodies (NCT05225415), and another indication, dry AMD (NCT05893537). The crystal structure of S2R complexed with zervimesine to 2.74 Å resolution reveals this investigational therapeutic bound in the binding site of S2R analogous to that seen previously with other S2R ligands, and is consistent with binding affinity data from a S2R competition assay. The structural interactions by which zervimesine binds with S2R are illuminated, which may shed light on the potential structure-function relationship underlying the favorable effects of zervimesine seen preclinically and clinically, and may foster the design of future S2R modulators for neurodegenerative conditions.
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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.