dihexa
Some animal studies reported better spatial learning and neuronal markers with Dihexa. Other animal findings were negative, key early papers carry a notice of concern or retraction, and the major Alzheimer’s trial of its fosgonimeton prodrug missed its clinical endpoints.
Angiotensin-IV-derived peptidomimetic
- Also ATH-1001 / PNB-0408
- Human exposure through a prodrug
- Retractions affect early evidence
What is Dihexa?
Dihexa is an experimental angiotensin-IV-derived peptidomimetic studied for effects on neuronal signaling and cognition. It is also called ATH-1001 or PNB-0408.
ATH-1001 is the active metabolite measured in human plasma after participants received the prodrug fosgonimeton. Directly administered Dihexa is a different intervention.
FDA identity record · the aliases matter
Official chemical identity record
FDA Substance Registration System, UNII 9WYX65A5C2.
The record lists ATH-1001 and PNB-0408 as synonyms for Dihexa. A substance identifier does not mean FDA review or approval.
The identity record does not authenticate a commercial product.
Read the original sourceFDA identity relationship · active moiety
Official chemical identity record
FDA Global Substance Registration System.
The full substance record links Dihexa as the active moiety of fosgonimeton sodium.
Fosgonimeton is a prodrug, so its administration data do not describe direct Dihexa dosing.
Read the original sourceFosgonimeton phase 1 · human active-metabolite exposure
Randomized phase 1 trial of a prodrug
Journal of Alzheimer's disease : JAD. PMID 35180125.
The randomized program enrolled 88 participants across healthy-young, healthy-older and Alzheimer’s cohorts, including placebo recipients. Plasma assays measured ATH-1001 after subcutaneous fosgonimeton. The Alzheimer’s cohort contained only 11 participants.
- Participants / model
- 48 healthy young men, 29 healthy older adults, and 11 people with Alzheimer’s disease, across drug and placebo groups.
- Follow-up
- Single-dose cohorts; repeated-dose cohorts treated for nine days.
This establishes human exposure to the active metabolite after fosgonimeton. It does not establish a dose or cognitive benefit for directly administered Dihexa products.
Read the original sourceWhy do some of the early studies need a warning?
A prominent 2014 mechanism paper was retracted in 2025. The 2013 foundational Dihexa paper has a notice of concern.
| Paper | Evidence status | Consequence |
|---|---|---|
| 2013 metabolically stabilized AngIV analogs | Notice of concern issued in 2021. | The original findings no longer provide settled confirmation. |
| 2014 HGF/c-Met mechanism paper | Retracted in 2025. | The results no longer provide reliable support for the mechanism. |
| 2012 related HGF/Met-modifier paper | Retracted in 2025. | A second retraction affects the same research lineage. |
2013 foundational paper · notice of concern
Editorial notice of concern
The Journal of pharmacology and experimental therapeutics. PMID 34551989.
A 2021 notice of concern applies to the 2013 paper on metabolically stabilized angiotensin IV analogs, including Dihexa.
A notice of concern is distinct from a retraction, but it leaves the reliability of the original findings unresolved.
Read the original source2014 mechanism paper · retracted in 2025
Retraction notice
The Journal of pharmacology and experimental therapeutics. PMID 40312093.
The journal retracted the 2014 paper linking the procognitive and synaptogenic effects of angiotensin IV-derived peptides to HGF/c-Met activation.
The journal retracted the experiments in 2025, so they no longer provide reliable support for the mechanism.
Read the original source2012 related paper · retracted in 2025
Retraction notice
The Journal of pharmacology and experimental therapeutics. PMID 40312092.
A related paper about developing angiotensin IV analogs as HGF/Met modifiers was retracted in 2025.
This separate paper from the same research lineage was also retracted in 2025.
Read the original sourceWhat is the proposed HGF/MET mechanism?
The development program proposes that Dihexa enhances signaling through HGF and its MET receptor, with downstream effects on neuronal survival and connections.
Later cell and rodent work reported synaptic and cognitive effects, while the foundational mechanism paper was retracted. Neither synapse markers nor a proposed pathway shows improved memory in a person.
2023 fosgonimeton research · cells and rodents
Sponsor-associated preclinical experiments
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics. PMID 36538176.
The study reported neuronal and cognitive effects of the active metabolite in cell and rodent models, alongside development of fosgonimeton as a prodrug.
This development-program study used cells and rodents, with no human clinical outcome.
Read the original source2014 mechanism paper · retracted in 2025
Retraction notice
The Journal of pharmacology and experimental therapeutics. PMID 40312093.
The journal retracted the 2014 paper linking the procognitive and synaptogenic effects of angiotensin IV-derived peptides to HGF/c-Met activation.
The journal retracted the experiments in 2025, so they no longer provide reliable support for the mechanism.
Read the original sourceDo the animal studies consistently show better cognition?
Animal findings conflict. Some models produced positive results, while a 2024 toxin-exposed rat study found no protection against induced weight, motor, or cognitive deficits.
| Study | Result | Limit |
|---|---|---|
| 2021 Chinese APP/PS1 mouse study | Improved spatial learning and several neuronal/inflammatory measurements. | A mouse Alzheimer’s model, not patients with dementia. |
| 2023 development-program research | Positive neuronal and cognitive findings in cells and rodents. | Sponsor-associated preclinical work. |
| 2024 toxin-exposed rats | No protection against the induced weight, motor and cognitive deficits. | A specific Huntington’s-like model. |
Chinese Dihexa study · Alzheimer’s mouse model
Animal experiments
Brain sciences. PMID 34827486.
A Nanjing research group reported better spatial learning and changes in neuronal and inflammatory markers in APP/PS1 mice treated with Dihexa. Experiments implicated PI3K/AKT signaling.
- Participants / model
- APP/PS1 mice; a genetic model used in Alzheimer’s research.
Published in English by researchers at China Pharmaceutical University and Nanjing First Hospital. It does not establish treatment of Alzheimer’s disease in people.
Read the original source2023 fosgonimeton research · cells and rodents
Sponsor-associated preclinical experiments
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics. PMID 36538176.
The study reported neuronal and cognitive effects of the active metabolite in cell and rodent models, alongside development of fosgonimeton as a prodrug.
This development-program study used cells and rodents, with no human clinical outcome.
Read the original source2024 rat study · no protection in this model
Animal experiment with negative findings
Journal of Huntington's disease. PMID 38489193.
Forty male rats were randomized across control, toxin, and toxin-plus-Dihexa groups. Dihexa, named PNB-0408, did not protect against the weight, motor and cognitive deficits induced by 3-nitropropionic acid.
- Participants / model
- 40 male Wistar rats.
- Follow-up
- Five weeks
A toxin-induced Huntington’s-like model is not Alzheimer’s disease or ordinary aging. Dihexa nevertheless failed to protect against deficits in this model.
Read the original sourceHas Dihexa been tested in people?
People have been exposed to its active molecule through fosgonimeton treatment. That is different from a clinical trial of directly taking Dihexa.
The phase 1 study measured ATH-1001 in human plasma after subcutaneous fosgonimeton. Its 11-person Alzheimer’s cohort studied electrical brain-response measures and did not measure improved memory or daily function.
FDA identity record · the aliases matter
Official chemical identity record
FDA Substance Registration System, UNII 9WYX65A5C2.
The record lists ATH-1001 and PNB-0408 as synonyms for Dihexa. A substance identifier does not mean FDA review or approval.
The identity record does not authenticate a commercial product.
Read the original sourceFosgonimeton phase 1 · human active-metabolite exposure
Randomized phase 1 trial of a prodrug
Journal of Alzheimer's disease : JAD. PMID 35180125.
The randomized program enrolled 88 participants across healthy-young, healthy-older and Alzheimer’s cohorts, including placebo recipients. Plasma assays measured ATH-1001 after subcutaneous fosgonimeton. The Alzheimer’s cohort contained only 11 participants.
- Participants / model
- 48 healthy young men, 29 healthy older adults, and 11 people with Alzheimer’s disease, across drug and placebo groups.
- Follow-up
- Single-dose cohorts; repeated-dose cohorts treated for nine days.
This establishes human exposure to the active metabolite after fosgonimeton. It does not establish a dose or cognitive benefit for directly administered Dihexa products.
Read the original sourceWhy does the formulation matter?
Fosgonimeton is a prodrug developed to deliver the active metabolite. Direct oral or injected Dihexa can have different absorption and exposure. A study of one cannot authenticate the contents or establish the dosing of another.
FDA identity relationship · active moiety
Official chemical identity record
FDA Global Substance Registration System.
The full substance record links Dihexa as the active moiety of fosgonimeton sodium.
Fosgonimeton is a prodrug, so its administration data do not describe direct Dihexa dosing.
Read the original sourceFosgonimeton phase 1 · human active-metabolite exposure
Randomized phase 1 trial of a prodrug
Journal of Alzheimer's disease : JAD. PMID 35180125.
The randomized program enrolled 88 participants across healthy-young, healthy-older and Alzheimer’s cohorts, including placebo recipients. Plasma assays measured ATH-1001 after subcutaneous fosgonimeton. The Alzheimer’s cohort contained only 11 participants.
- Participants / model
- 48 healthy young men, 29 healthy older adults, and 11 people with Alzheimer’s disease, across drug and placebo groups.
- Follow-up
- Single-dose cohorts; repeated-dose cohorts treated for nine days.
This establishes human exposure to the active metabolite after fosgonimeton. It does not establish a dose or cognitive benefit for directly administered Dihexa products.
Read the original sourceDirect Dihexa dosing versus a prodrug
Literature and registry record set
ClinicalTrials.gov, PubMed, and FDA chemical identity records.
The cited records include a fosgonimeton pharmacokinetic study and published human prodrug studies. They contain no controlled efficacy trial of directly administered retail-style oral or injected Dihexa.
A molecule formed after a prodrug can have human exposure data even when direct administration is untested.
Read the original sourceDid fosgonimeton improve Alzheimer’s outcomes?
The LIFT-AD trial did not show a statistically significant improvement in its primary combined cognition/function endpoint or its secondary cognitive and daily-function endpoints at 26 weeks.
The primary analysis included 287 people with mild-to-moderate Alzheimer’s disease who were not taking acetylcholinesterase inhibitors. The broader safety population contained 549 people, so efficacy and safety percentages use different denominators.
LIFT-AD · no significant clinical benefit
Randomized phase 2/3 trial of a prodrug
Journal of Alzheimer's disease reports. PMID 41393340.
The phase 2/3 trial missed its primary combined cognition/function endpoint and its secondary cognition and daily-function endpoints at 26 weeks. The primary analysis included 287 people with mild-to-moderate Alzheimer’s disease not taking acetylcholinesterase inhibitors.
- Adverse-event discontinuation: 14.2% with fosgonimeton versus 4.6% with placebo, mostly injection-site reactions.
- The primary endpoint p value was 0.70; cognition and daily-function endpoints were also not significant.
- Participants / model
- Primary efficacy analysis: 287. Broader safety population: 549, including other dose and concomitant-treatment groups.
- Treatment
- Subcutaneous fosgonimeton versus placebo.
- Follow-up
- 26 weeks
No demonstrated benefit in these endpoints. This was not a trial of an oral Dihexa product or healthy-person cognitive enhancement.
Read the original sourceIs Dihexa’s half-life known in humans?
There are human active-metabolite measurements after fosgonimeton. They do not define the half-life of a directly administered Dihexa product.
The phase 1 report estimated an ATH-1001 plasma half-life of about 1.5 hours, with an occasional longer terminal phase at very low concentrations. Neither value establishes the duration of a cognitive effect.
Fosgonimeton phase 1 · human active-metabolite exposure
Randomized phase 1 trial of a prodrug
Journal of Alzheimer's disease : JAD. PMID 35180125.
The randomized program enrolled 88 participants across healthy-young, healthy-older and Alzheimer’s cohorts, including placebo recipients. Plasma assays measured ATH-1001 after subcutaneous fosgonimeton. The Alzheimer’s cohort contained only 11 participants.
- Participants / model
- 48 healthy young men, 29 healthy older adults, and 11 people with Alzheimer’s disease, across drug and placebo groups.
- Follow-up
- Single-dose cohorts; repeated-dose cohorts treated for nine days.
This establishes human exposure to the active metabolite after fosgonimeton. It does not establish a dose or cognitive benefit for directly administered Dihexa products.
Read the original sourceDoes it permanently build new brain connections?
The cited human studies did not measure permanent beneficial synapse growth or lasting cognitive gain from directly administered Dihexa. Animal structural findings cannot answer that question in people.
2023 fosgonimeton research · cells and rodents
Sponsor-associated preclinical experiments
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics. PMID 36538176.
The study reported neuronal and cognitive effects of the active metabolite in cell and rodent models, alongside development of fosgonimeton as a prodrug.
This development-program study used cells and rodents, with no human clinical outcome.
Read the original sourceLIFT-AD · no significant clinical benefit
Randomized phase 2/3 trial of a prodrug
Journal of Alzheimer's disease reports. PMID 41393340.
The phase 2/3 trial missed its primary combined cognition/function endpoint and its secondary cognition and daily-function endpoints at 26 weeks. The primary analysis included 287 people with mild-to-moderate Alzheimer’s disease not taking acetylcholinesterase inhibitors.
- Adverse-event discontinuation: 14.2% with fosgonimeton versus 4.6% with placebo, mostly injection-site reactions.
- The primary endpoint p value was 0.70; cognition and daily-function endpoints were also not significant.
- Participants / model
- Primary efficacy analysis: 287. Broader safety population: 549, including other dose and concomitant-treatment groups.
- Treatment
- Subcutaneous fosgonimeton versus placebo.
- Follow-up
- 26 weeks
No demonstrated benefit in these endpoints. This was not a trial of an oral Dihexa product or healthy-person cognitive enhancement.
Read the original sourceDirect Dihexa dosing versus a prodrug
Literature and registry record set
ClinicalTrials.gov, PubMed, and FDA chemical identity records.
The cited records include a fosgonimeton pharmacokinetic study and published human prodrug studies. They contain no controlled efficacy trial of directly administered retail-style oral or injected Dihexa.
A molecule formed after a prodrug can have human exposure data even when direct administration is untested.
Read the original sourceWhat adverse effects have been reported?
The fosgonimeton trial provides some relevant human safety information, but there is no validated adverse-effect profile for directly administered Dihexa products.
In LIFT-AD, 14.2% of fosgonimeton recipients stopped because of adverse events versus 4.6% with placebo, mostly because of injection-site reactions. Those rates describe that study treatment, not an oral Dihexa product.
LIFT-AD · no significant clinical benefit
Randomized phase 2/3 trial of a prodrug
Journal of Alzheimer's disease reports. PMID 41393340.
The phase 2/3 trial missed its primary combined cognition/function endpoint and its secondary cognition and daily-function endpoints at 26 weeks. The primary analysis included 287 people with mild-to-moderate Alzheimer’s disease not taking acetylcholinesterase inhibitors.
- Adverse-event discontinuation: 14.2% with fosgonimeton versus 4.6% with placebo, mostly injection-site reactions.
- The primary endpoint p value was 0.70; cognition and daily-function endpoints were also not significant.
- Participants / model
- Primary efficacy analysis: 287. Broader safety population: 549, including other dose and concomitant-treatment groups.
- Treatment
- Subcutaneous fosgonimeton versus placebo.
- Follow-up
- 26 weeks
No demonstrated benefit in these endpoints. This was not a trial of an oral Dihexa product or healthy-person cognitive enhancement.
Read the original sourceDirect Dihexa dosing versus a prodrug
Literature and registry record set
ClinicalTrials.gov, PubMed, and FDA chemical identity records.
The cited records include a fosgonimeton pharmacokinetic study and published human prodrug studies. They contain no controlled efficacy trial of directly administered retail-style oral or injected Dihexa.
A molecule formed after a prodrug can have human exposure data even when direct administration is untested.
Read the original sourceDoes “no established profile” mean no side effects?
No. It means reliable rates, a tolerated direct-dose range and longer-term risks have not been established for that use. Anonymous reports cannot determine how often a drug caused a symptom.
Direct Dihexa dosing versus a prodrug
Literature and registry record set
ClinicalTrials.gov, PubMed, and FDA chemical identity records.
The cited records include a fosgonimeton pharmacokinetic study and published human prodrug studies. They contain no controlled efficacy trial of directly administered retail-style oral or injected Dihexa.
A molecule formed after a prodrug can have human exposure data even when direct administration is untested.
Read the original sourceDoes Dihexa cause cancer?
The cited human studies did not measure cancer incidence after direct Dihexa use. They cannot estimate or rule out long-term cancer risk.
The proposed target is a growth-factor signaling system. Short neuronal experiments and symptom reports did not evaluate tumor risk from sustained exposure, and the foundational mechanism paper was retracted.
2023 fosgonimeton research · cells and rodents
Sponsor-associated preclinical experiments
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics. PMID 36538176.
The study reported neuronal and cognitive effects of the active metabolite in cell and rodent models, alongside development of fosgonimeton as a prodrug.
This development-program study used cells and rodents, with no human clinical outcome.
Read the original source2014 mechanism paper · retracted in 2025
Retraction notice
The Journal of pharmacology and experimental therapeutics. PMID 40312093.
The journal retracted the 2014 paper linking the procognitive and synaptogenic effects of angiotensin IV-derived peptides to HGF/c-Met activation.
The journal retracted the experiments in 2025, so they no longer provide reliable support for the mechanism.
Read the original sourceLIFT-AD · no significant clinical benefit
Randomized phase 2/3 trial of a prodrug
Journal of Alzheimer's disease reports. PMID 41393340.
The phase 2/3 trial missed its primary combined cognition/function endpoint and its secondary cognition and daily-function endpoints at 26 weeks. The primary analysis included 287 people with mild-to-moderate Alzheimer’s disease not taking acetylcholinesterase inhibitors.
- Adverse-event discontinuation: 14.2% with fosgonimeton versus 4.6% with placebo, mostly injection-site reactions.
- The primary endpoint p value was 0.70; cognition and daily-function endpoints were also not significant.
- Participants / model
- Primary efficacy analysis: 287. Broader safety population: 549, including other dose and concomitant-treatment groups.
- Treatment
- Subcutaneous fosgonimeton versus placebo.
- Follow-up
- 26 weeks
No demonstrated benefit in these endpoints. This was not a trial of an oral Dihexa product or healthy-person cognitive enhancement.
Read the original sourceIs there a proven Dihexa regimen?
The cited evidence establishes no validated direct-administration regimen, combination plan, or stopping schedule.
Fosgonimeton trial doses describe a different administered molecule and cannot be copied onto Dihexa. The cited evidence does not establish a nootropic cycle, interaction list, or lasting benefit after stopping.
Fosgonimeton phase 1 · human active-metabolite exposure
Randomized phase 1 trial of a prodrug
Journal of Alzheimer's disease : JAD. PMID 35180125.
The randomized program enrolled 88 participants across healthy-young, healthy-older and Alzheimer’s cohorts, including placebo recipients. Plasma assays measured ATH-1001 after subcutaneous fosgonimeton. The Alzheimer’s cohort contained only 11 participants.
- Participants / model
- 48 healthy young men, 29 healthy older adults, and 11 people with Alzheimer’s disease, across drug and placebo groups.
- Follow-up
- Single-dose cohorts; repeated-dose cohorts treated for nine days.
This establishes human exposure to the active metabolite after fosgonimeton. It does not establish a dose or cognitive benefit for directly administered Dihexa products.
Read the original sourceLIFT-AD · no significant clinical benefit
Randomized phase 2/3 trial of a prodrug
Journal of Alzheimer's disease reports. PMID 41393340.
The phase 2/3 trial missed its primary combined cognition/function endpoint and its secondary cognition and daily-function endpoints at 26 weeks. The primary analysis included 287 people with mild-to-moderate Alzheimer’s disease not taking acetylcholinesterase inhibitors.
- Adverse-event discontinuation: 14.2% with fosgonimeton versus 4.6% with placebo, mostly injection-site reactions.
- The primary endpoint p value was 0.70; cognition and daily-function endpoints were also not significant.
- Participants / model
- Primary efficacy analysis: 287. Broader safety population: 549, including other dose and concomitant-treatment groups.
- Treatment
- Subcutaneous fosgonimeton versus placebo.
- Follow-up
- 26 weeks
No demonstrated benefit in these endpoints. This was not a trial of an oral Dihexa product or healthy-person cognitive enhancement.
Read the original sourceDirect Dihexa dosing versus a prodrug
Literature and registry record set
ClinicalTrials.gov, PubMed, and FDA chemical identity records.
The cited records include a fosgonimeton pharmacokinetic study and published human prodrug studies. They contain no controlled efficacy trial of directly administered retail-style oral or injected Dihexa.
A molecule formed after a prodrug can have human exposure data even when direct administration is untested.
Read the original sourceDoes an FDA substance record mean it is approved?
No. FDA explicitly states that having a UNII substance identifier does not imply regulatory review or approval.
The identity record connects Dihexa, ATH-1001, and PNB-0408. It does not show that an online product is approved, accurately labeled, or equivalent to clinical-study material.
FDA identity record · the aliases matter
Official chemical identity record
FDA Substance Registration System, UNII 9WYX65A5C2.
The record lists ATH-1001 and PNB-0408 as synonyms for Dihexa. A substance identifier does not mean FDA review or approval.
The identity record does not authenticate a commercial product.
Read the original sourceStudies and sources
FDA identity record · the aliases matter
Official chemical identity record
FDA Substance Registration System, UNII 9WYX65A5C2.
The record lists ATH-1001 and PNB-0408 as synonyms for Dihexa. A substance identifier does not mean FDA review or approval.
The identity record does not authenticate a commercial product.
Read the original sourceFDA identity relationship · active moiety
Official chemical identity record
FDA Global Substance Registration System.
The full substance record links Dihexa as the active moiety of fosgonimeton sodium.
Fosgonimeton is a prodrug, so its administration data do not describe direct Dihexa dosing.
Read the original sourceFosgonimeton phase 1 · human active-metabolite exposure
Randomized phase 1 trial of a prodrug
Journal of Alzheimer's disease : JAD. PMID 35180125.
The randomized program enrolled 88 participants across healthy-young, healthy-older and Alzheimer’s cohorts, including placebo recipients. Plasma assays measured ATH-1001 after subcutaneous fosgonimeton. The Alzheimer’s cohort contained only 11 participants.
- Participants / model
- 48 healthy young men, 29 healthy older adults, and 11 people with Alzheimer’s disease, across drug and placebo groups.
- Follow-up
- Single-dose cohorts; repeated-dose cohorts treated for nine days.
This establishes human exposure to the active metabolite after fosgonimeton. It does not establish a dose or cognitive benefit for directly administered Dihexa products.
Read the original sourceLIFT-AD · no significant clinical benefit
Randomized phase 2/3 trial of a prodrug
Journal of Alzheimer's disease reports. PMID 41393340.
The phase 2/3 trial missed its primary combined cognition/function endpoint and its secondary cognition and daily-function endpoints at 26 weeks. The primary analysis included 287 people with mild-to-moderate Alzheimer’s disease not taking acetylcholinesterase inhibitors.
- Adverse-event discontinuation: 14.2% with fosgonimeton versus 4.6% with placebo, mostly injection-site reactions.
- The primary endpoint p value was 0.70; cognition and daily-function endpoints were also not significant.
- Participants / model
- Primary efficacy analysis: 287. Broader safety population: 549, including other dose and concomitant-treatment groups.
- Treatment
- Subcutaneous fosgonimeton versus placebo.
- Follow-up
- 26 weeks
No demonstrated benefit in these endpoints. This was not a trial of an oral Dihexa product or healthy-person cognitive enhancement.
Read the original source2013 foundational paper · notice of concern
Editorial notice of concern
The Journal of pharmacology and experimental therapeutics. PMID 34551989.
A 2021 notice of concern applies to the 2013 paper on metabolically stabilized angiotensin IV analogs, including Dihexa.
A notice of concern is distinct from a retraction, but it leaves the reliability of the original findings unresolved.
Read the original source2014 mechanism paper · retracted in 2025
Retraction notice
The Journal of pharmacology and experimental therapeutics. PMID 40312093.
The journal retracted the 2014 paper linking the procognitive and synaptogenic effects of angiotensin IV-derived peptides to HGF/c-Met activation.
The journal retracted the experiments in 2025, so they no longer provide reliable support for the mechanism.
Read the original source2012 related paper · retracted in 2025
Retraction notice
The Journal of pharmacology and experimental therapeutics. PMID 40312092.
A related paper about developing angiotensin IV analogs as HGF/Met modifiers was retracted in 2025.
This separate paper from the same research lineage was also retracted in 2025.
Read the original sourceChinese Dihexa study · Alzheimer’s mouse model
Animal experiments
Brain sciences. PMID 34827486.
A Nanjing research group reported better spatial learning and changes in neuronal and inflammatory markers in APP/PS1 mice treated with Dihexa. Experiments implicated PI3K/AKT signaling.
- Participants / model
- APP/PS1 mice; a genetic model used in Alzheimer’s research.
Published in English by researchers at China Pharmaceutical University and Nanjing First Hospital. It does not establish treatment of Alzheimer’s disease in people.
Read the original source2024 rat study · no protection in this model
Animal experiment with negative findings
Journal of Huntington's disease. PMID 38489193.
Forty male rats were randomized across control, toxin, and toxin-plus-Dihexa groups. Dihexa, named PNB-0408, did not protect against the weight, motor and cognitive deficits induced by 3-nitropropionic acid.
- Participants / model
- 40 male Wistar rats.
- Follow-up
- Five weeks
A toxin-induced Huntington’s-like model is not Alzheimer’s disease or ordinary aging. Dihexa nevertheless failed to protect against deficits in this model.
Read the original source2023 fosgonimeton research · cells and rodents
Sponsor-associated preclinical experiments
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics. PMID 36538176.
The study reported neuronal and cognitive effects of the active metabolite in cell and rodent models, alongside development of fosgonimeton as a prodrug.
This development-program study used cells and rodents, with no human clinical outcome.
Read the original sourceDirect Dihexa dosing versus a prodrug
Literature and registry record set
ClinicalTrials.gov, PubMed, and FDA chemical identity records.
The cited records include a fosgonimeton pharmacokinetic study and published human prodrug studies. They contain no controlled efficacy trial of directly administered retail-style oral or injected Dihexa.
A molecule formed after a prodrug can have human exposure data even when direct administration is untested.
Read the original sourceWhy is dihexa in D tier?
D tier follows unresolved benefit and safety, affected foundational publications, and a negative major clinical trial of the related prodrug. The active molecule did reach human plasma after fosgonimeton administration, but direct Dihexa dosing remains untested in a controlled efficacy trial.