Peptide LibraryTrofinetide
Also known as: Daybue, Daybue Stix, NNZ-2566
Trofinetide (also called Daybue or Daybue Stix) is an FDA-approved oral tripeptide analog for Rett syndrome. The FDA label says the way trofinetide works in Rett syndrome is unknown. It is a synthetic analog of glycine-proline-glutamate, the N-terminal tripeptide of IGF-1, with a methyl group on the proline that gave it a longer half-life and better oral absorption than the parent peptide.
For research use only.
Key Facts
- CAS
- 853400-76-7
- Molecular Weight (MW)
- 315.33 g/mol
- Half-life
- Effective half-life about 1.5 hours
- FDA status
- Approved
- Evidence level
- FDA Approved
- Human dose established
- Yes
- Administration Route
- Oral · Gastrostomy tube
- Frequency
- Twice daily, morning and evening
- Last updated
- Oct 30, 2026
- Reviewed
- Oct 30, 2026
Research summary
FDA-approved treatment for Rett syndrome (Daybue, Daybue Stix) in adults and children aged 2 and older. A synthetic analog of a tripeptide from IGF-1, taken twice daily by weight, and its mechanism is unknown.
Research evidence
- Regulatory review (FDA label)1 reviewed source
- Controlled human trials4 reviewed sources
- Early or uncontrolled human studies3 reviewed sources
- Lab & animal studies1 reviewed source
How it works
Each step shows whether the sources Peptide Library has reviewed include that kind of research. Counts are reviewed sources, not every study ever published. Reviews and programme summaries that describe human use are shown as "reported", not as trials, and registered trials without published results are listed but not counted. A higher step means research has progressed further; it does not mean a compound works better or is safer. Compounds whose evidence has not been reviewed yet show "Not reviewed" instead of a guess.
Peptide Library's Trofinetide profile summarises 7 cited studies listed in the Science section, the compound's regulatory status, and research-protocol parameters reported for it. It is a research reference, not medical advice.
Trofinetide dosage evidence
Trofinetide has an FDA-approved human dosage. As Daybue (oral solution) and Daybue Stix (powder packets), it is taken twice daily by weight, from 5,000 mg at 9 kg to under 12 kg up to 12,000 mg at 50 kg and above, for Rett syndrome in adults and children aged 2 and older. The label halves these doses in moderate kidney impairment and does not recommend use in severe impairment.
| Human dosing established | Yes |
|---|---|
| Studied dose range | 5,000–12,000 mg twice daily, by body weight |
| Route | Oral · Gastrostomy tube |
| Frequency | Twice daily, morning and evening |
| Duration studied | Continuous |
| Titration | None. The dose is set by weight band: 5,000 mg at 9 to under 12 kg, 6,000 mg at 12 to under 20 kg, 8,000 mg at 20 to under 35 kg, 10,000 mg at 35 to under 50 kg, and 12,000 mg at 50 kg and above. Severe diarrhea, suspected dehydration, significant weight loss or severe vomiting can mean interrupting, reducing or stopping treatment. |
| Half-life | Effective half-life about 1.5 hours |
| Evidence level | FDA Approved |
| Last reviewed | 2026-10-30 |
Research-reported dosing
Doses as studied, one row per regimen. Different trials used different regimens; they are listed separately rather than averaged.
| Study / context | Population | Dose | Route | Frequency | Duration | Outcome studied | Source |
|---|---|---|---|---|---|---|---|
| FDA label — Daybue and Daybue StixFDA-approved label · FDA prescribing information | Adults and children aged 2 and older with Rett syndrome | 5,000 to 12,000 mg by body weight; 2,500 to 6,000 mg in moderate kidney impairment | Oral or gastrostomy tube | Twice daily | Continuous | Treatment of Rett syndrome | DAYBUE (trofinetide) oral solution and DAYBUE STIX for oral solution — FDA prescribing information, DailyMed |
| Neul et al., 2023 — LAVENDER, phase 3Clinical trial · Randomised, double-blind, placebo-controlled phase 3 | Girls and women aged 5 to 20 with Rett syndrome and a MECP2 mutation (93 on trofinetide, 94 on placebo) | By body weight | Oral or gastrostomy tube | Twice daily | 12 weeks | RSBQ score improved by 4.9 points versus 1.7 on placebo; CGI-I at week 12 was 3.5 versus 3.8 | Neul JL et al. Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study. Nat Med. 2023. |
| Percy et al., 2024 — LILAC, open-label extensionClinical trial · Open-label extension | Girls and women aged 5 to 21 from LAVENDER (n=154) | By body weight | Oral or gastrostomy tube | Twice daily | 40 weeks | Symptom scores continued to improve; diarrhea led 21.4% of participants to withdraw | Percy AK et al. Trofinetide for the treatment of Rett syndrome: Results from the open-label extension LILAC study. Med. 2024. |
| Percy et al., 2025 — DAFFODIL, phase 2/3Clinical trial · Open-label phase 2/3 | Girls aged 2 to 4 with Rett syndrome (n=15) | By body weight | Oral or gastrostomy tube | Twice daily | 12 weeks, then about 21 months | Weight-based dosing reached the target exposure; diarrhea in 80% and vomiting in 53.3% | Percy AK et al. Results from the phase 2/3 DAFFODIL study of trofinetide in girls aged 2-4 years with Rett syndrome. Med. 2025. |
| Glaze et al., 2019 — pediatric Rett syndrome, phase 2Clinical trial · Randomised, double-blind, placebo-controlled phase 2 | Girls aged 5 to 15 with Rett syndrome (n=82) | 50, 100 or 200 mg/kg | Oral | Twice daily | 42 days after a 14-day placebo lead-in | Improvement over placebo at 200 mg/kg on RSBQ, a clinician scale and CGI-I | Glaze DG et al. Double-blind, randomized, placebo-controlled study of trofinetide in pediatric Rett syndrome. Neurology. 2019. |
| Glaze et al., 2017 — adolescent and adult Rett syndrome, phase 2Clinical trial · Exploratory, randomised, double-blind, placebo-controlled phase 2 | Adolescent and adult females with Rett syndrome (n=56) | 35 or 70 mg/kg | Oral | Twice daily | 14 or 28 days | Efficacy trends at 70 mg/kg by prespecified criteria | Glaze DG et al. A Double-Blind, Randomized, Placebo-Controlled Clinical Study of Trofinetide in the Treatment of Rett Syndrome. Pediatr Neurol. 2017. |
| Berry-Kravis et al., 2020 — fragile X syndrome, phase 2 (not an approved use)Clinical trial · Exploratory, randomised, double-blind, placebo-controlled phase 2 | Adolescent and adult males with fragile X syndrome (n=72) | 35 or 70 mg/kg | Oral | Twice daily | 28 days | A signal of efficacy at 70 mg/kg on a composite analysis | Berry-Kravis E et al. A Double-Blind, Randomized, Placebo-Controlled Clinical Study of Trofinetide in the Treatment of Fragile X Syndrome. Pediatr Neurol. 2020. |
| NCT00805818 — traumatic brain injury, phase 2 (not an approved use)Clinical trial · Phase 2 trial, registry record | Patients with traumatic brain injury (n=261) | 20 mg/kg bolus, then 1, 3 or 6 mg/kg/h | Intravenous | — | 72 hours | Completed; no results posted on the registry | NCT00805818 — Study of NNZ-2566 in Patients With Traumatic Brain Injury |
Preclinical and analog research
Not human dosing evidence. Listed for completeness and never extrapolated to a human dose.
| Study / context | Population | Dose | Route | Frequency | Duration | Outcome studied | Source |
|---|---|---|---|---|---|---|---|
| Preclinical — focal stroke in ratsPreclinical · Rodent study | Rats | 3 to 10 mg/kg/h for 4 hours intravenously, or 30 to 60 mg/kg by mouth; not convertible to a human dose | Intravenous or oral | — | — | Smaller infarct area after induced stroke | Bickerdike MJ et al. NNZ-2566: a Gly-Pro-Glu analogue with neuroprotective efficacy in a rat model of acute focal stroke. J Neurol Sci. 2009. |
Where sources disagree
- The label says the mechanism in Rett syndrome is unknown. Trofinetide is an analog of glycine-proline-glutamate, the N-terminal tripeptide of IGF-1, but it is not IGF-1, and IGF-1 doses and data do not apply to it.
- The phase 3 effect was statistically significant but modest: a 3.2-point difference from placebo on the 90-point RSBQ, and 0.3 points on the 7-point CGI-I.
- LAVENDER enrolled girls and women aged 5 to 20. Use from age 2 rests on that trial plus pharmacokinetic and safety data in 15 children, and the label has no data in people aged 65 and older.
- Phase 2 trials used mg/kg doses. The weight bands on the label were designed to give similar exposure across patients, so the two sets of numbers are not directly comparable.
- Tolerability shapes real use. In LAVENDER, the label reports diarrhea in 82% (80.6% in the published paper), and 19% withdrew because of adverse reactions, most often diarrhea (15%).
- DAFFODIL shows as terminated on the registry because the sponsor ended it after the 2023 approval to switch participants to the commercial product.
Handling & administration
- Reconstitution Guide
- No reconstitution for Daybue, a ready-to-use oral solution. Daybue Stix powder is dissolved in cold or room-temperature water or a water-based drink and taken right away.
Sequence & molecular data
| Amino acid sequence | Gly-(2-methyl)Pro-Glu |
|---|---|
| Molecular formula | C13H21N3O6 |
| Molecular weight | 315.33 g/mol |
| CAS number | 853400-76-7 |
| Half-life | Effective half-life about 1.5 hours |
| Appearance | Pink to red oral solution (Daybue); white to off-white or pinkish powder in packets (Daybue Stix) |
| Formulation | Oral solution |
| PubChem CID | 11318905 |
| FDA UNII | Z2ME8F52QL |
| ChEMBL | CHEMBL197084 |
| DrugBank | DB06045 |
| KEGG | D12400 |
Identifiers link to the public PubChem, FDA Substance Registration (UNII), ChEMBL and DrugBank records for the same entity.
Science
Mechanism of Action
The FDA label says the way trofinetide works in Rett syndrome is unknown. It is a synthetic analog of glycine-proline-glutamate, the N-terminal tripeptide of IGF-1, with a methyl group on the proline that gave it a longer half-life and better oral absorption than the parent peptide. In rodents, it reduced injury in a stroke model and corrected some deficits in a fragile X mouse model. Those findings do not establish how it acts in people.
Origin
Synthetic analog of Gly-Pro-Glu developed by Neuren Pharmaceuticals as NNZ-2566; the US product is from Acadia Pharmaceuticals.
Studies
- Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study
- Trofinetide for the treatment of Rett syndrome: Results from the open-label extension LILAC study
- Results from the phase 2/3 DAFFODIL study of trofinetide in girls aged 2-4 years with Rett syndrome
- Double-blind, randomized, placebo-controlled study of trofinetide in pediatric Rett syndrome
- A Double-Blind, Randomized, Placebo-Controlled Clinical Study of Trofinetide in the Treatment of Fragile X Syndrome
- NNZ-2566, a novel analog of (1-3) IGF-1, as a potential therapeutic agent for fragile X syndrome
- NNZ-2566: a Gly-Pro-Glu analogue with neuroprotective efficacy in a rat model of acute focal stroke
Research statistics
67 PubMed publications · 47.5% human clinical research · 13 registered trials
Counts of published research through 2026-11-01, not evidence that it works. Publications by year, study types and trials · How publications are counted
Regulatory & research status
Trofinetide is an FDA-approved product for specific labelled indications. Approval does not extend to the research contexts described on this page, and approved products are prescription medicines.
| FDA status | Approved |
|---|---|
| Research status | Approved product (see FDA status) |
| Availability | Prescription-Only |
| WADA (sport) | Unknown / Not Listed |
| Library classification | FDA-Approved |
How FDA approval, compounding and research-only status differ
Benefits
Trofinetide side effects
The effects below are drawn from Trofinetide's prescribing information, which lists the full adverse-reaction data.
Side Effects
- Diarrhea (82% versus 20% on placebo)
- Vomiting (29% versus 12%)
- Fever (9% versus 4%)
- Seizure (9% versus 6%)
- Anxiety, decreased appetite and fatigue (each 8% versus 1% to 2%)
Storage & stability
This compound is not supplied as a powder to be mixed, so the freeze-dried powder and reconstitution handling described for research peptides does not apply. Storage conditions are product-specific: follow the label or packaging of the product itself.
Trofinetide: frequently asked questions
What is trofinetide?
Trofinetide is a medicine for Rett syndrome, a rare genetic neurodevelopmental disorder, sold as Daybue oral solution and Daybue Stix powder packets. It is a small synthetic molecule modeled on a three-amino-acid fragment of IGF-1, and it was the first treatment approved for Rett syndrome in the US.
How does trofinetide work?
Nobody knows for certain. The FDA label says its mechanism in Rett syndrome is unknown. It was designed as a more stable analog of glycine-proline-glutamate, a tripeptide cut from IGF-1 in the brain, and it showed neuroprotective effects in rodent studies.
Is trofinetide FDA approved?
Yes. FDA approved Daybue oral solution on 10 March 2023 (NDA 217026, Acadia) and Daybue Stix for oral solution on 11 December 2025 (NDA 219884). Both are for Rett syndrome in adults and children aged 2 and older.
What is the labeled dose of trofinetide?
The FDA label sets a twice-daily dose by weight, from 5,000 mg at 9 kg to under 12 kg up to 12,000 mg at 50 kg and above, by mouth or gastrostomy tube. Moderate kidney impairment halves these doses, and use is not recommended in severe impairment. This is reference information, not medical advice.
What are the side effects of trofinetide?
Diarrhea is the main one, in 82% of patients versus 20% on placebo in the phase 3 trial, followed by vomiting (29% versus 12%). The label also warns about weight loss and about aspiration after vomiting. This is reference information, not medical advice.
How well does trofinetide work?
In the 12-week LAVENDER trial, caregiver-rated symptoms improved by 4.9 points versus 1.7 on placebo on a 90-point scale, and clinician ratings were slightly better, at 3.5 versus 3.8 on a 7-point scale. The results were statistically significant, but the difference was modest.
What is the half-life of trofinetide?
The label gives an effective elimination half-life of about 1.5 hours in healthy adults. About 80% of a dose is excreted unchanged in the urine, and the label lowers the dose in moderate kidney impairment.
Is trofinetide the same as IGF-1?
No. IGF-1 is a 70-amino-acid hormone, while trofinetide is a modified three-amino-acid analog of the fragment at its N-terminal end, weighing about 315 g/mol. It is taken by mouth at gram doses, and IGF-1 data do not apply to it.
What compounds are similar to trofinetide?
This library lists IGF-1, mecasermin, davunetide and cerebrolysin alongside trofinetide because they share a growth-factor origin or a neurological research area. They are not equivalents, and only trofinetide is approved for Rett syndrome.
References
- DAYBUE (trofinetide) oral solution and DAYBUE STIX for oral solution — FDA prescribing information, DailyMedExternal reference
- Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study — Nat Med, 2023External reference
- Trofinetide for the treatment of Rett syndrome: Results from the open-label extension LILAC study — Med, 2024External reference
- Results from the phase 2/3 DAFFODIL study of trofinetide in girls aged 2-4 years with Rett syndrome — Med, 2025External reference
- Double-blind, randomized, placebo-controlled study of trofinetide in pediatric Rett syndrome — Neurology, 2019External reference
- A Double-Blind, Randomized, Placebo-Controlled Clinical Study of Trofinetide in the Treatment of Rett Syndrome — Pediatr Neurol, 2017External reference
- A Double-Blind, Randomized, Placebo-Controlled Clinical Study of Trofinetide in the Treatment of Fragile X Syndrome — Pediatr Neurol, 2020External reference
- NNZ-2566, a novel analog of (1-3) IGF-1, as a potential therapeutic agent for fragile X syndrome — Neuromolecular Med, 2015External reference
- NNZ-2566: a Gly-Pro-Glu analogue with neuroprotective efficacy in a rat model of acute focal stroke — J Neurol Sci, 2009External reference
- NCT00805818 — NNZ-2566 in traumatic brain injury, phase 2External reference
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Compiled by Peptide Library Editorial · Reviewed Oct 30, 2026 · Updated Oct 30, 2026 · Version 1
This Trofinetide profile is compiled from published literature (7 cited studies linked above), public regulatory records and chemical registries. It describes what research reports; it is not medical advice, and nothing here is a dosing recommendation for humans. Peptide Library does not sell peptides. Editorial policy · How profiles are compiled · Report an error
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