ACD856

updated

ACD856 is an unapproved investigational compound that the developer's papers describe as a Trk receptor positive allosteric modulator potentiating NGF and BDNF signaling. Three early-phase studies in healthy volunteers report no serious adverse events, but no study tests it in patients. The supplier's cholinergic mechanism claim is not what the published work describes, and no public chemical record gives a structure for anything sold under the name.

Trk receptor positive allosteric modulator

  • PubChem name lookups for ACD856, ACD-856 and ACD 856 returned no compound on 9 October 2026, so no structure, formula or CAS number is established.
  • An openFDA Drugs@FDA query for ACD856 returned no application on 9 October 2026.
  • Human data come from three developer studies in healthy volunteers: a microdose in 6 men, single doses of 1 to 150 mg in 56 subjects, and 7 days of 10, 30 or 90 mg daily in 24 subjects.
  • The half-life was about 20 hours, and the authors report no treatment-emergent or dose-related adverse events and no serious adverse events.
  • ACD856 potentiated TrkA and TrkB signaling with EC50 values of 0.38 and 0.30 micromolar; the only acetylcholine result belongs to the predecessor ACD855.
  • Registry searches on 9 October 2026 found no phase 2 study and no study in people with Alzheimer's disease.

What is ACD856, and is it approved?

ACD856 is an investigational Trk receptor modulator with no FDA approval record, and no public chemical record gives its structure. An openFDA query for ACD856 returned no application on 9 October 2026.

PubChem name lookups for ACD856, ACD-856 and ACD 856 returned no compound on 9 October 2026, so no structure, formula, molecular weight or CAS number is established here for anything sold under this name. Material from a vendor cannot be matched to the developer's molecule from a public chemical record.

The developer's screening paper reports that a 25,000-molecule screen identified the triazinetrione derivatives ACD855, which it identifies as ponazuril (PubChem CID 3050408, C18H14F3N3O6S, 457.4 g/mol, CAS 69004-04-2), and later ACD856. ACD855 and ACD856 are different molecules, and data for one do not transfer to the other.

An openFDA Drugs@FDA query for ACD856 returned no application on 9 October 2026. That is a dated, US-scoped search, and approvals outside the United States are not covered here. All human data found come from three early-phase studies in healthy volunteers by the developer: a phase 0 microdose and two phase 1 studies.

Developer screening paper: ACD856 potentiates TrkA and TrkB

Animal study

Dahlström M et al. Cells. 2021;10(8). PMID 34440640.

A 25,000-molecule screen identified the triazinetrione derivatives ACD855, which the paper identifies as ponazuril (PubChem CID 3050408, C18H14F3N3O6S, 457.4 g/mol, CAS 69004-04-2), and later ACD856. The screen looked for small molecules that potentiate signaling of the neurotrophins NGF and BDNF, and ACD856 potentiated TrkA and TrkB signaling with EC50 values of 0.38 and 0.30 micromolar. The compounds acted as cognitive enhancers in a TrkB-dependent manner in several behavioral models, and a single treatment with ACD856 restored age-related cognitive dysfunction in 18-month-old mice to the level of 2-month-old mice. In the abstract, the only acetylcholine result, a 40% rise in hippocampal acetylcholine, and the rat brain-slice long-term potentiation result are reported for the predecessor ACD855, not for ACD856.

Participants / model
Cell-based receptor assays; mice, including 18-month-old mice
Treatment
In vitro exposure; single in vivo treatment (route not stated in the abstract)
Follow-up
Single treatment in the aged-mouse test
Study design
Preclinical screen with receptor assays and behavioral memory tests
Funding
not stated in the source

Developer authors. ACD855 and ACD856 are different molecules, and data for one do not transfer to the other. PubChem name lookups for ACD856, ACD-856 and ACD 856 returned no compound on 9 October 2026.

Read the original source
FDA record search, 9 October 2026: no matching application

Regulatory record

U.S. Food and Drug Administration, openFDA Drugs@FDA API query run on 9 October 2026 for ACD856 by brand or generic name.

The query for ACD856 returned no application. No US approval record was found. This supports only a dated, US-scoped statement.

Participants / model
FDA application database, not a clinical population
Treatment
Name search
Follow-up
Query run on 9 October 2026
Study design
Dated US approval-record search
Funding
not stated in the source

A search result shows what the database returned on that date. It is not a worldwide status claim.

Read the original source

What did the phase 0 and phase 1 trials find?

In three early studies in healthy volunteers, the authors report no treatment-emergent or dose-related adverse events and no serious adverse events. The studies measured safety, PK, CSF levels and EEG, not any cognitive outcome.

A phase 0 intravenous microdose (0.100 mg) was given to 6 healthy men, followed by a randomized, double-blind, placebo-controlled single ascending oral dose study (1 to 150 mg) in 56 healthy subjects. The authors report no treatment-emergent or dose-related adverse events or other safety findings. After the microdose, plasma decline was bi-exponential with low distribution volume, low clearance and a half-life of about 20 hours. Orally, absorption was rapid, bioavailability almost complete and exposure dose-proportional. Food lowered and delayed Cmax but had little effect on half-life or overall bioavailability, and no renal elimination was detected.

In the multiple ascending dose study, 24 healthy men and women in 3 cohorts of 8 (6 on ACD856 and 2 on placebo per cohort) took 10, 30 or 90 mg once daily for 7 days as an oral solution. There were no serious adverse events and no treatment-emergent or dose-related trends in any safety assessment, which included anxiety, depression and suicidality questionnaires. Tmax was 30 to 45 minutes, steady state came before day 6, steady-state half-life was about 20 hours, and accumulation ratios were about 1.6 for Cmax and 1.9 for AUC. No unchanged ACD856 appeared in urine, and CSF levels rose with dose.

In the 30 and 90 mg cohorts, quantitative EEG showed dose-dependent increases in relative theta power and decreases in fast alpha and beta power, which the authors read as central target engagement. An EEG change is not a cognitive outcome, and the abstract reports no cognitive test. The predecessor ACD855 had a half-life in humans too long to allow further development.

Phase 0 and phase 1: 6 men (microdose) and 56 volunteers (single doses)

Clinical trial

Nilsson B et al. Eur J Clin Pharmacol. 2024;80(5):717-727. PMID 38353689.

The authors report no treatment-emergent or dose-related adverse events or other safety findings. After the microdose, plasma decline was bi-exponential with low distribution volume, low clearance, and a half-life of about 20 hours. Orally, absorption was rapid, bioavailability almost complete, and exposure dose-proportional; food lowered and delayed Cmax but had little effect on half-life or overall bioavailability; no renal elimination was detected. The predecessor ACD855 had a half-life in humans too long to allow further development.

Participants / model
6 healthy men (microdose); 56 healthy subjects, including placebo (single ascending dose)
Treatment
Intravenous microdose 0.100 mg; single oral doses 1 to 150 mg
Follow-up
Single doses
Study design
Phase 0 intravenous microdose, then a randomized, double-blind, placebo-controlled single ascending oral dose study
Funding
not stated in the source

Developer authors. Registered as NCT05783830 (microdose, retrospectively registered) and NCT05077631 (single ascending dose).

Read the original source
Phase 1 multiple doses: 24 volunteers, 7 days, CSF and EEG

Clinical trial

Önnestam K et al. J Prev Alzheimers Dis. 2023;10(4):778-789. PMID 37874100.

There were no serious adverse events and no treatment-emergent or dose-related trends in any safety assessment, which included anxiety, depression, and suicidality questionnaires. Tmax was 30 to 45 minutes, steady state came before day 6, steady-state half-life was about 20 hours, and accumulation ratios were about 1.6 for Cmax and 1.9 for AUC. No unchanged ACD856 appeared in urine. CSF levels rose with dose. In the 30 and 90 mg cohorts, quantitative EEG showed dose-dependent increases in relative theta power and decreases in fast alpha and beta power, which the authors read as central target engagement.

Participants / model
24 healthy male and female subjects (6 active and 2 placebo per cohort, in 3 cohorts of 8)
Treatment
Oral solution, 10, 30 or 90 mg once daily, or placebo
Follow-up
7 days
Study design
Phase 1 multiple ascending dose study with PK in plasma, urine and CSF and quantitative EEG
Funding
not stated in the source

Developer authors. An EEG change is not a cognitive outcome, and the abstract reports no cognitive test.

Read the original source

Which ACD856 studies are registered?

Three ACD856 studies are registered, all completed and none with posted results. Registry searches on 9 October 2026 found no phase 2 study and no study in people with Alzheimer's disease.

ClinicalTrials.gov lists three ACD856 studies, all completed and none with posted results: the multiple ascending dose study (NCT05077501, phase 1, enrollment 24), the single ascending dose study (NCT05077631, phase 1, enrollment 56) and the microdose study (NCT05783830, early phase 1, enrollment 6). The microdose study was registered retrospectively.

Registry searches for ACD856 and for AlzeCure on 9 October 2026 found no phase 2 study and no study in people with Alzheimer's disease. Development status after the 2024 papers is not established here.

Registry: three completed early-phase studies, no results posted

Trial registry record

ClinicalTrials.gov. NCT05077501 (multiple ascending dose), with related records NCT05077631 (single ascending dose) and NCT05783830 (microdose).

Three ACD856 studies are listed, all completed and none with posted results: the multiple ascending dose study (NCT05077501, phase 1, enrollment 24), the single ascending dose study (NCT05077631, phase 1, enrollment 56), and the microdose study (NCT05783830, early phase 1, enrollment 6). Registry searches for ACD856 and for AlzeCure on 9 October 2026 found no phase 2 study and no study in people with Alzheimer's disease.

Participants / model
Registry records, not a population
Treatment
Not applicable
Follow-up
Not applicable
Study design
Official trial registry
Funding
not stated in the source

No posted results for any of the three records.

Read the original source
Phase 0 and phase 1: 6 men (microdose) and 56 volunteers (single doses)

Clinical trial

Nilsson B et al. Eur J Clin Pharmacol. 2024;80(5):717-727. PMID 38353689.

The authors report no treatment-emergent or dose-related adverse events or other safety findings. After the microdose, plasma decline was bi-exponential with low distribution volume, low clearance, and a half-life of about 20 hours. Orally, absorption was rapid, bioavailability almost complete, and exposure dose-proportional; food lowered and delayed Cmax but had little effect on half-life or overall bioavailability; no renal elimination was detected. The predecessor ACD855 had a half-life in humans too long to allow further development.

Participants / model
6 healthy men (microdose); 56 healthy subjects, including placebo (single ascending dose)
Treatment
Intravenous microdose 0.100 mg; single oral doses 1 to 150 mg
Follow-up
Single doses
Study design
Phase 0 intravenous microdose, then a randomized, double-blind, placebo-controlled single ascending oral dose study
Funding
not stated in the source

Developer authors. Registered as NCT05783830 (microdose, retrospectively registered) and NCT05077631 (single ascending dose).

Read the original source

What do the cell and animal studies show?

In cells and mice, ACD856 potentiated TrkA and TrkB signaling, enhanced neurite outgrowth, raised BDNF and restored memory in aged mice. These are developer studies, and none has been tested in people.

In the developer's screening paper, ACD856 potentiated TrkA and TrkB signaling with EC50 values of 0.38 and 0.30 micromolar. The compounds acted as cognitive enhancers in a TrkB-dependent manner in several behavioral models, and a single treatment with ACD856 restored age-related cognitive dysfunction in 18-month-old mice to the level of 2-month-old mice.

In cell lines, primary cortical neurons and mice, ACD856 enhanced NGF-induced neurite outgrowth, raised the presynaptic protein SNAP25, increased phosphorylated TrkB, protected neurons against amyloid-beta or energy-deprivation toxicity, and increased BDNF, including in the brains of 21-month-old mice. Repeated dosing gave an antidepressant-like effect that lasted up to seven days. The paper describes these effects as neuroprotective and possibly disease-modifying; neither has been tested in people.

In the forced swim test, ACD855, ACD856 and a third Trk modulator (AC26845) each showed antidepressant-like activity. The authors report data indicating that the forced-swim effects of fluoxetine and ketamine are mediated through BDNF/TrkB signaling. No depression outcome in people exists in the records found. The abstracts for these studies do not state the route or dose.

Developer screening paper: ACD856 potentiates TrkA and TrkB

Animal study

Dahlström M et al. Cells. 2021;10(8). PMID 34440640.

A 25,000-molecule screen identified the triazinetrione derivatives ACD855, which the paper identifies as ponazuril (PubChem CID 3050408, C18H14F3N3O6S, 457.4 g/mol, CAS 69004-04-2), and later ACD856. The screen looked for small molecules that potentiate signaling of the neurotrophins NGF and BDNF, and ACD856 potentiated TrkA and TrkB signaling with EC50 values of 0.38 and 0.30 micromolar. The compounds acted as cognitive enhancers in a TrkB-dependent manner in several behavioral models, and a single treatment with ACD856 restored age-related cognitive dysfunction in 18-month-old mice to the level of 2-month-old mice. In the abstract, the only acetylcholine result, a 40% rise in hippocampal acetylcholine, and the rat brain-slice long-term potentiation result are reported for the predecessor ACD855, not for ACD856.

Participants / model
Cell-based receptor assays; mice, including 18-month-old mice
Treatment
In vitro exposure; single in vivo treatment (route not stated in the abstract)
Follow-up
Single treatment in the aged-mouse test
Study design
Preclinical screen with receptor assays and behavioral memory tests
Funding
not stated in the source

Developer authors. ACD855 and ACD856 are different molecules, and data for one do not transfer to the other. PubChem name lookups for ACD856, ACD-856 and ACD 856 returned no compound on 9 October 2026.

Read the original source
Cells and aged mice: neurite outgrowth, neuroprotection, BDNF

Animal study

Parrado Fernandez C et al. Int J Mol Sci. 2023;24(13). PMID 37446337.

In cell lines, primary cortical neurons, and mice, ACD856 enhanced NGF-induced neurite outgrowth, raised the presynaptic protein SNAP25, increased phosphorylated TrkB, protected neurons against amyloid-beta or energy-deprivation toxicity, and increased BDNF, including in the brains of 21-month-old mice. Repeated dosing gave an antidepressant-like effect that lasted up to seven days. The paper describes these effects as neuroprotective and possibly disease-modifying; neither has been tested in people.

Participants / model
PC12 and SH-SY5Y cells, primary cortical neurons, 21-month-old mice; species for the antidepressant test not stated in the abstract
Treatment
In vitro exposure; repeated in vivo dosing (route not stated in the abstract)
Follow-up
Repeated dosing; effect lasted up to seven days
Study design
Preclinical study of neurite outgrowth, SNAP25, TrkB phosphorylation, neuroprotection, brain BDNF and antidepressant-like behavior
Funding
not stated in the source

Developer authors. The abstract does not give a route or dose.

Read the original source
Forced swim test: antidepressant-like activity in rodents

Animal study

Madjid N et al. Psychopharmacology (Berl). 2023;240(8):1789-1804. PMID 37394539.

In the forced swim test, ACD855, ACD856, and a third Trk modulator (AC26845) each showed antidepressant-like activity, and the authors report data indicating that the forced-swim effects of fluoxetine and ketamine are mediated through BDNF/TrkB signaling. Microdialysis measured neurotransmitter levels in freely moving rats.

Participants / model
Rodents in the forced swim test; freely moving rats for microdialysis
Treatment
Not stated in the abstract
Follow-up
not stated in the source
Study design
Preclinical study of forced swim behavior and brain neurotransmitter levels
Funding
not stated in the source

Developer authors. No depression outcome in people exists in the records found.

Read the original source

Is ACD856 a cholinergic compound with a mechanism distinct from BDNF-pathway compounds?

No. Every ACD856 record found describes it as a Trk receptor potentiator of NGF and BDNF signaling, and the one acetylcholine result belongs to the predecessor ACD855. No record tests ACD856 in Alzheimer's disease or against any racetam.

Sellers describe ACD856 as cognitive enhancement through cholinergic potentiation, in development for Alzheimer's disease, with a mechanism distinct from racetams and BDNF-pathway compounds.

A PubMed search on 9 October 2026 for ACD856, ACD-856 or "ACD 856" returned 12 records, 6 of them about this compound (3 preclinical reports, 1 review, and 2 phase 1 studies in healthy volunteers); the other 6 were unrelated matches. All 6 describe ACD856 as a Trk receptor positive allosteric modulator that potentiates NGF and BDNF signaling, which contradicts the claim of a mechanism distinct from BDNF-pathway compounds.

A separate search for ACD856 with cholinergic or acetylcholine returned 1 record, the screening paper. In its abstract, the only acetylcholine result, a 40% rise in hippocampal acetylcholine, is reported for ACD855, not ACD856. No record tests ACD856 in people with Alzheimer's disease or compares it with any racetam.

The development goal for Alzheimer's disease is accurate as a stated aim. Cognitive enhancement in people has not been tested.

PubMed search, 9 October 2026: 12 records, 6 about ACD856, all describe Trk potentiation

PubMed search record

PubMed search run on 9 October 2026: ACD856 OR ACD-856 OR "ACD 856". 12 records returned.

The search returned 12 records, 6 of them about this compound (3 preclinical reports, 1 review, and 2 phase 1 studies in healthy volunteers); the other 6 were unrelated matches. All 6 describe ACD856 as a Trk receptor positive allosteric modulator that potentiates NGF and BDNF signaling, which contradicts the claim of a mechanism distinct from BDNF-pathway compounds. A separate search for ACD856 with cholinergic or acetylcholine returned 1 record, whose acetylcholine result belongs to ACD855. No record tests ACD856 in people with Alzheimer's disease or compares it with any racetam.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Search run on 9 October 2026
Study design
Literature search
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists.

Read the original source
Developer screening paper: ACD856 potentiates TrkA and TrkB

Animal study

Dahlström M et al. Cells. 2021;10(8). PMID 34440640.

A 25,000-molecule screen identified the triazinetrione derivatives ACD855, which the paper identifies as ponazuril (PubChem CID 3050408, C18H14F3N3O6S, 457.4 g/mol, CAS 69004-04-2), and later ACD856. The screen looked for small molecules that potentiate signaling of the neurotrophins NGF and BDNF, and ACD856 potentiated TrkA and TrkB signaling with EC50 values of 0.38 and 0.30 micromolar. The compounds acted as cognitive enhancers in a TrkB-dependent manner in several behavioral models, and a single treatment with ACD856 restored age-related cognitive dysfunction in 18-month-old mice to the level of 2-month-old mice. In the abstract, the only acetylcholine result, a 40% rise in hippocampal acetylcholine, and the rat brain-slice long-term potentiation result are reported for the predecessor ACD855, not for ACD856.

Participants / model
Cell-based receptor assays; mice, including 18-month-old mice
Treatment
In vitro exposure; single in vivo treatment (route not stated in the abstract)
Follow-up
Single treatment in the aged-mouse test
Study design
Preclinical screen with receptor assays and behavioral memory tests
Funding
not stated in the source

Developer authors. ACD855 and ACD856 are different molecules, and data for one do not transfer to the other. PubChem name lookups for ACD856, ACD-856 and ACD 856 returned no compound on 9 October 2026.

Read the original source

How does ACD856 work, and what does the body do with it?

ACD856 is described as a Trk receptor positive allosteric modulator that potentiates NGF and BDNF signaling. In healthy volunteers its half-life was about 20 hours and CSF levels rose with dose.

The published mechanism is Trk receptor potentiation. The screen looked for small molecules that potentiate signaling of the neurotrophins NGF and BDNF, and ACD856 potentiated TrkA and TrkB signaling with EC50 values of 0.38 and 0.30 micromolar. The paper reports the effects as TrkB-dependent in several behavioral models in mice.

After a 0.100 mg intravenous microdose in 6 healthy men, plasma decline was bi-exponential with low distribution volume, low clearance and a half-life of about 20 hours. Orally, absorption was rapid, bioavailability almost complete and exposure dose-proportional, and food lowered and delayed Cmax with little effect on half-life or overall bioavailability.

In the 7-day multiple-dose study, Tmax was 30 to 45 minutes, steady state came before day 6, steady-state half-life was about 20 hours, and accumulation ratios were about 1.6 for Cmax and 1.9 for AUC. No unchanged ACD856 appeared in urine. CSF levels rose with dose, and quantitative EEG changes in the 30 and 90 mg cohorts were read by the authors as central target engagement.

Developer screening paper: ACD856 potentiates TrkA and TrkB

Animal study

Dahlström M et al. Cells. 2021;10(8). PMID 34440640.

A 25,000-molecule screen identified the triazinetrione derivatives ACD855, which the paper identifies as ponazuril (PubChem CID 3050408, C18H14F3N3O6S, 457.4 g/mol, CAS 69004-04-2), and later ACD856. The screen looked for small molecules that potentiate signaling of the neurotrophins NGF and BDNF, and ACD856 potentiated TrkA and TrkB signaling with EC50 values of 0.38 and 0.30 micromolar. The compounds acted as cognitive enhancers in a TrkB-dependent manner in several behavioral models, and a single treatment with ACD856 restored age-related cognitive dysfunction in 18-month-old mice to the level of 2-month-old mice. In the abstract, the only acetylcholine result, a 40% rise in hippocampal acetylcholine, and the rat brain-slice long-term potentiation result are reported for the predecessor ACD855, not for ACD856.

Participants / model
Cell-based receptor assays; mice, including 18-month-old mice
Treatment
In vitro exposure; single in vivo treatment (route not stated in the abstract)
Follow-up
Single treatment in the aged-mouse test
Study design
Preclinical screen with receptor assays and behavioral memory tests
Funding
not stated in the source

Developer authors. ACD855 and ACD856 are different molecules, and data for one do not transfer to the other. PubChem name lookups for ACD856, ACD-856 and ACD 856 returned no compound on 9 October 2026.

Read the original source
Phase 0 and phase 1: 6 men (microdose) and 56 volunteers (single doses)

Clinical trial

Nilsson B et al. Eur J Clin Pharmacol. 2024;80(5):717-727. PMID 38353689.

The authors report no treatment-emergent or dose-related adverse events or other safety findings. After the microdose, plasma decline was bi-exponential with low distribution volume, low clearance, and a half-life of about 20 hours. Orally, absorption was rapid, bioavailability almost complete, and exposure dose-proportional; food lowered and delayed Cmax but had little effect on half-life or overall bioavailability; no renal elimination was detected. The predecessor ACD855 had a half-life in humans too long to allow further development.

Participants / model
6 healthy men (microdose); 56 healthy subjects, including placebo (single ascending dose)
Treatment
Intravenous microdose 0.100 mg; single oral doses 1 to 150 mg
Follow-up
Single doses
Study design
Phase 0 intravenous microdose, then a randomized, double-blind, placebo-controlled single ascending oral dose study
Funding
not stated in the source

Developer authors. Registered as NCT05783830 (microdose, retrospectively registered) and NCT05077631 (single ascending dose).

Read the original source
Phase 1 multiple doses: 24 volunteers, 7 days, CSF and EEG

Clinical trial

Önnestam K et al. J Prev Alzheimers Dis. 2023;10(4):778-789. PMID 37874100.

There were no serious adverse events and no treatment-emergent or dose-related trends in any safety assessment, which included anxiety, depression, and suicidality questionnaires. Tmax was 30 to 45 minutes, steady state came before day 6, steady-state half-life was about 20 hours, and accumulation ratios were about 1.6 for Cmax and 1.9 for AUC. No unchanged ACD856 appeared in urine. CSF levels rose with dose. In the 30 and 90 mg cohorts, quantitative EEG showed dose-dependent increases in relative theta power and decreases in fast alpha and beta power, which the authors read as central target engagement.

Participants / model
24 healthy male and female subjects (6 active and 2 placebo per cohort, in 3 cohorts of 8)
Treatment
Oral solution, 10, 30 or 90 mg once daily, or placebo
Follow-up
7 days
Study design
Phase 1 multiple ascending dose study with PK in plasma, urine and CSF and quantitative EEG
Funding
not stated in the source

Developer authors. An EEG change is not a cognitive outcome, and the abstract reports no cognitive test.

Read the original source

What risks did the studies report?

The authors report no serious adverse events and no dose-related safety findings. Exposure was limited to single doses up to 150 mg and 7 days at up to 90 mg daily in healthy volunteers, so tolerability in patients and over longer use is unknown.

In the single-dose studies in 6 and 56 healthy volunteers, the authors report no treatment-emergent or dose-related adverse events or other safety findings. In the 7-day multiple-dose study in 24 healthy men and women, there were no serious adverse events and no treatment-emergent or dose-related trends in any safety assessment, including anxiety, depression and suicidality questionnaires.

Human exposure is limited to single doses up to 150 mg and 7 days at up to 90 mg daily in healthy volunteers, and every study comes from the developer. No study found tests ACD856 in patients, so safety in patients, in older adults and with longer use is not described.

Phase 0 and phase 1: 6 men (microdose) and 56 volunteers (single doses)

Clinical trial

Nilsson B et al. Eur J Clin Pharmacol. 2024;80(5):717-727. PMID 38353689.

The authors report no treatment-emergent or dose-related adverse events or other safety findings. After the microdose, plasma decline was bi-exponential with low distribution volume, low clearance, and a half-life of about 20 hours. Orally, absorption was rapid, bioavailability almost complete, and exposure dose-proportional; food lowered and delayed Cmax but had little effect on half-life or overall bioavailability; no renal elimination was detected. The predecessor ACD855 had a half-life in humans too long to allow further development.

Participants / model
6 healthy men (microdose); 56 healthy subjects, including placebo (single ascending dose)
Treatment
Intravenous microdose 0.100 mg; single oral doses 1 to 150 mg
Follow-up
Single doses
Study design
Phase 0 intravenous microdose, then a randomized, double-blind, placebo-controlled single ascending oral dose study
Funding
not stated in the source

Developer authors. Registered as NCT05783830 (microdose, retrospectively registered) and NCT05077631 (single ascending dose).

Read the original source
Phase 1 multiple doses: 24 volunteers, 7 days, CSF and EEG

Clinical trial

Önnestam K et al. J Prev Alzheimers Dis. 2023;10(4):778-789. PMID 37874100.

There were no serious adverse events and no treatment-emergent or dose-related trends in any safety assessment, which included anxiety, depression, and suicidality questionnaires. Tmax was 30 to 45 minutes, steady state came before day 6, steady-state half-life was about 20 hours, and accumulation ratios were about 1.6 for Cmax and 1.9 for AUC. No unchanged ACD856 appeared in urine. CSF levels rose with dose. In the 30 and 90 mg cohorts, quantitative EEG showed dose-dependent increases in relative theta power and decreases in fast alpha and beta power, which the authors read as central target engagement.

Participants / model
24 healthy male and female subjects (6 active and 2 placebo per cohort, in 3 cohorts of 8)
Treatment
Oral solution, 10, 30 or 90 mg once daily, or placebo
Follow-up
7 days
Study design
Phase 1 multiple ascending dose study with PK in plasma, urine and CSF and quantitative EEG
Funding
not stated in the source

Developer authors. An EEG change is not a cognitive outcome, and the abstract reports no cognitive test.

Read the original source

Why does ACD856 sit in C tier?

ACD856 has a defined mechanism, consistent preclinical data and clean early-phase safety and PK, but no efficacy result in any patient group. Every study comes from the developer, and its cholinergic mechanism claim is not what the published work describes.

The C reflects consistent developer preclinical data in cells, aged mice and rodent depression models, and clean safety and PK in three early-phase studies in healthy volunteers (6, 56 and 24 participants), with CSF exposure and EEG changes showing it reaches the brain.

Against that, there is no efficacy result in any patient population, no phase 2 registration, no exposure longer than 7 days, and every study comes from the developer. On the supplier's claims, the Alzheimer's development goal is accurate, but the cholinergic mechanism is not what the published work describes, and cognitive enhancement in people has not been tested.

Phase 0 and phase 1: 6 men (microdose) and 56 volunteers (single doses)

Clinical trial

Nilsson B et al. Eur J Clin Pharmacol. 2024;80(5):717-727. PMID 38353689.

The authors report no treatment-emergent or dose-related adverse events or other safety findings. After the microdose, plasma decline was bi-exponential with low distribution volume, low clearance, and a half-life of about 20 hours. Orally, absorption was rapid, bioavailability almost complete, and exposure dose-proportional; food lowered and delayed Cmax but had little effect on half-life or overall bioavailability; no renal elimination was detected. The predecessor ACD855 had a half-life in humans too long to allow further development.

Participants / model
6 healthy men (microdose); 56 healthy subjects, including placebo (single ascending dose)
Treatment
Intravenous microdose 0.100 mg; single oral doses 1 to 150 mg
Follow-up
Single doses
Study design
Phase 0 intravenous microdose, then a randomized, double-blind, placebo-controlled single ascending oral dose study
Funding
not stated in the source

Developer authors. Registered as NCT05783830 (microdose, retrospectively registered) and NCT05077631 (single ascending dose).

Read the original source
Phase 1 multiple doses: 24 volunteers, 7 days, CSF and EEG

Clinical trial

Önnestam K et al. J Prev Alzheimers Dis. 2023;10(4):778-789. PMID 37874100.

There were no serious adverse events and no treatment-emergent or dose-related trends in any safety assessment, which included anxiety, depression, and suicidality questionnaires. Tmax was 30 to 45 minutes, steady state came before day 6, steady-state half-life was about 20 hours, and accumulation ratios were about 1.6 for Cmax and 1.9 for AUC. No unchanged ACD856 appeared in urine. CSF levels rose with dose. In the 30 and 90 mg cohorts, quantitative EEG showed dose-dependent increases in relative theta power and decreases in fast alpha and beta power, which the authors read as central target engagement.

Participants / model
24 healthy male and female subjects (6 active and 2 placebo per cohort, in 3 cohorts of 8)
Treatment
Oral solution, 10, 30 or 90 mg once daily, or placebo
Follow-up
7 days
Study design
Phase 1 multiple ascending dose study with PK in plasma, urine and CSF and quantitative EEG
Funding
not stated in the source

Developer authors. An EEG change is not a cognitive outcome, and the abstract reports no cognitive test.

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Registry: three completed early-phase studies, no results posted

Trial registry record

ClinicalTrials.gov. NCT05077501 (multiple ascending dose), with related records NCT05077631 (single ascending dose) and NCT05783830 (microdose).

Three ACD856 studies are listed, all completed and none with posted results: the multiple ascending dose study (NCT05077501, phase 1, enrollment 24), the single ascending dose study (NCT05077631, phase 1, enrollment 56), and the microdose study (NCT05783830, early phase 1, enrollment 6). Registry searches for ACD856 and for AlzeCure on 9 October 2026 found no phase 2 study and no study in people with Alzheimer's disease.

Participants / model
Registry records, not a population
Treatment
Not applicable
Follow-up
Not applicable
Study design
Official trial registry
Funding
not stated in the source

No posted results for any of the three records.

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Developer screening paper: ACD856 potentiates TrkA and TrkB

Animal study

Dahlström M et al. Cells. 2021;10(8). PMID 34440640.

A 25,000-molecule screen identified the triazinetrione derivatives ACD855, which the paper identifies as ponazuril (PubChem CID 3050408, C18H14F3N3O6S, 457.4 g/mol, CAS 69004-04-2), and later ACD856. The screen looked for small molecules that potentiate signaling of the neurotrophins NGF and BDNF, and ACD856 potentiated TrkA and TrkB signaling with EC50 values of 0.38 and 0.30 micromolar. The compounds acted as cognitive enhancers in a TrkB-dependent manner in several behavioral models, and a single treatment with ACD856 restored age-related cognitive dysfunction in 18-month-old mice to the level of 2-month-old mice. In the abstract, the only acetylcholine result, a 40% rise in hippocampal acetylcholine, and the rat brain-slice long-term potentiation result are reported for the predecessor ACD855, not for ACD856.

Participants / model
Cell-based receptor assays; mice, including 18-month-old mice
Treatment
In vitro exposure; single in vivo treatment (route not stated in the abstract)
Follow-up
Single treatment in the aged-mouse test
Study design
Preclinical screen with receptor assays and behavioral memory tests
Funding
not stated in the source

Developer authors. ACD855 and ACD856 are different molecules, and data for one do not transfer to the other. PubChem name lookups for ACD856, ACD-856 and ACD 856 returned no compound on 9 October 2026.

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PubMed search, 9 October 2026: 12 records, 6 about ACD856, all describe Trk potentiation

PubMed search record

PubMed search run on 9 October 2026: ACD856 OR ACD-856 OR "ACD 856". 12 records returned.

The search returned 12 records, 6 of them about this compound (3 preclinical reports, 1 review, and 2 phase 1 studies in healthy volunteers); the other 6 were unrelated matches. All 6 describe ACD856 as a Trk receptor positive allosteric modulator that potentiates NGF and BDNF signaling, which contradicts the claim of a mechanism distinct from BDNF-pathway compounds. A separate search for ACD856 with cholinergic or acetylcholine returned 1 record, whose acetylcholine result belongs to ACD855. No record tests ACD856 in people with Alzheimer's disease or compares it with any racetam.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Search run on 9 October 2026
Study design
Literature search
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists.

Read the original source

Studies and sources

Developer screening paper: ACD856 potentiates TrkA and TrkB

Animal study

Dahlström M et al. Cells. 2021;10(8). PMID 34440640.

A 25,000-molecule screen identified the triazinetrione derivatives ACD855, which the paper identifies as ponazuril (PubChem CID 3050408, C18H14F3N3O6S, 457.4 g/mol, CAS 69004-04-2), and later ACD856. The screen looked for small molecules that potentiate signaling of the neurotrophins NGF and BDNF, and ACD856 potentiated TrkA and TrkB signaling with EC50 values of 0.38 and 0.30 micromolar. The compounds acted as cognitive enhancers in a TrkB-dependent manner in several behavioral models, and a single treatment with ACD856 restored age-related cognitive dysfunction in 18-month-old mice to the level of 2-month-old mice. In the abstract, the only acetylcholine result, a 40% rise in hippocampal acetylcholine, and the rat brain-slice long-term potentiation result are reported for the predecessor ACD855, not for ACD856.

Participants / model
Cell-based receptor assays; mice, including 18-month-old mice
Treatment
In vitro exposure; single in vivo treatment (route not stated in the abstract)
Follow-up
Single treatment in the aged-mouse test
Study design
Preclinical screen with receptor assays and behavioral memory tests
Funding
not stated in the source

Developer authors. ACD855 and ACD856 are different molecules, and data for one do not transfer to the other. PubChem name lookups for ACD856, ACD-856 and ACD 856 returned no compound on 9 October 2026.

Read the original source
Cells and aged mice: neurite outgrowth, neuroprotection, BDNF

Animal study

Parrado Fernandez C et al. Int J Mol Sci. 2023;24(13). PMID 37446337.

In cell lines, primary cortical neurons, and mice, ACD856 enhanced NGF-induced neurite outgrowth, raised the presynaptic protein SNAP25, increased phosphorylated TrkB, protected neurons against amyloid-beta or energy-deprivation toxicity, and increased BDNF, including in the brains of 21-month-old mice. Repeated dosing gave an antidepressant-like effect that lasted up to seven days. The paper describes these effects as neuroprotective and possibly disease-modifying; neither has been tested in people.

Participants / model
PC12 and SH-SY5Y cells, primary cortical neurons, 21-month-old mice; species for the antidepressant test not stated in the abstract
Treatment
In vitro exposure; repeated in vivo dosing (route not stated in the abstract)
Follow-up
Repeated dosing; effect lasted up to seven days
Study design
Preclinical study of neurite outgrowth, SNAP25, TrkB phosphorylation, neuroprotection, brain BDNF and antidepressant-like behavior
Funding
not stated in the source

Developer authors. The abstract does not give a route or dose.

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Forced swim test: antidepressant-like activity in rodents

Animal study

Madjid N et al. Psychopharmacology (Berl). 2023;240(8):1789-1804. PMID 37394539.

In the forced swim test, ACD855, ACD856, and a third Trk modulator (AC26845) each showed antidepressant-like activity, and the authors report data indicating that the forced-swim effects of fluoxetine and ketamine are mediated through BDNF/TrkB signaling. Microdialysis measured neurotransmitter levels in freely moving rats.

Participants / model
Rodents in the forced swim test; freely moving rats for microdialysis
Treatment
Not stated in the abstract
Follow-up
not stated in the source
Study design
Preclinical study of forced swim behavior and brain neurotransmitter levels
Funding
not stated in the source

Developer authors. No depression outcome in people exists in the records found.

Read the original source
Phase 0 and phase 1: 6 men (microdose) and 56 volunteers (single doses)

Clinical trial

Nilsson B et al. Eur J Clin Pharmacol. 2024;80(5):717-727. PMID 38353689.

The authors report no treatment-emergent or dose-related adverse events or other safety findings. After the microdose, plasma decline was bi-exponential with low distribution volume, low clearance, and a half-life of about 20 hours. Orally, absorption was rapid, bioavailability almost complete, and exposure dose-proportional; food lowered and delayed Cmax but had little effect on half-life or overall bioavailability; no renal elimination was detected. The predecessor ACD855 had a half-life in humans too long to allow further development.

Participants / model
6 healthy men (microdose); 56 healthy subjects, including placebo (single ascending dose)
Treatment
Intravenous microdose 0.100 mg; single oral doses 1 to 150 mg
Follow-up
Single doses
Study design
Phase 0 intravenous microdose, then a randomized, double-blind, placebo-controlled single ascending oral dose study
Funding
not stated in the source

Developer authors. Registered as NCT05783830 (microdose, retrospectively registered) and NCT05077631 (single ascending dose).

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Phase 1 multiple doses: 24 volunteers, 7 days, CSF and EEG

Clinical trial

Önnestam K et al. J Prev Alzheimers Dis. 2023;10(4):778-789. PMID 37874100.

There were no serious adverse events and no treatment-emergent or dose-related trends in any safety assessment, which included anxiety, depression, and suicidality questionnaires. Tmax was 30 to 45 minutes, steady state came before day 6, steady-state half-life was about 20 hours, and accumulation ratios were about 1.6 for Cmax and 1.9 for AUC. No unchanged ACD856 appeared in urine. CSF levels rose with dose. In the 30 and 90 mg cohorts, quantitative EEG showed dose-dependent increases in relative theta power and decreases in fast alpha and beta power, which the authors read as central target engagement.

Participants / model
24 healthy male and female subjects (6 active and 2 placebo per cohort, in 3 cohorts of 8)
Treatment
Oral solution, 10, 30 or 90 mg once daily, or placebo
Follow-up
7 days
Study design
Phase 1 multiple ascending dose study with PK in plasma, urine and CSF and quantitative EEG
Funding
not stated in the source

Developer authors. An EEG change is not a cognitive outcome, and the abstract reports no cognitive test.

Read the original source
Registry: three completed early-phase studies, no results posted

Trial registry record

ClinicalTrials.gov. NCT05077501 (multiple ascending dose), with related records NCT05077631 (single ascending dose) and NCT05783830 (microdose).

Three ACD856 studies are listed, all completed and none with posted results: the multiple ascending dose study (NCT05077501, phase 1, enrollment 24), the single ascending dose study (NCT05077631, phase 1, enrollment 56), and the microdose study (NCT05783830, early phase 1, enrollment 6). Registry searches for ACD856 and for AlzeCure on 9 October 2026 found no phase 2 study and no study in people with Alzheimer's disease.

Participants / model
Registry records, not a population
Treatment
Not applicable
Follow-up
Not applicable
Study design
Official trial registry
Funding
not stated in the source

No posted results for any of the three records.

Read the original source

Why is ACD856 in C tier?

C fits a compound with a defined mechanism, consistent preclinical data and clean safety and PK in three early-phase studies in healthy volunteers. No efficacy result exists in any patient group, no phase 2 study is registered, the longest exposure was 7 days, and every study comes from the developer. The grade does not cover the supplier's cholinergic claim, which the published work contradicts.