RESEARCH MONOGRAPH · KDC-MN-125

Davunetide (NAP)

May 9, 2026 Kodiac biolabs Research Revised May 30, 2026 2 min read

Our opinion on this compound

63/100

ADNP-derived neuroprotective octapeptide that survived a discouraging PSP trial. Still mechanistically interesting

Davunetide (NAPVSIPQ, often abbreviated NAP) is an octapeptide fragment derived from activity-dependent neuroprotective protein (ADNP), discovered by the Gozes group at Tel Aviv University in the late 1990s. ADNP itself is a transcription factor essential for embryonic brain development (ADNP haploinsufficiency causes a rare neurodevelopmental syndrome), and NAP was identified as a small fragment that recapitulated some of the neuroprotective activity in cell-culture models.

The preclinical case is unusually broad. NAP showed protection against multiple neurodegenerative insults in animal models (amyloid-beta toxicity, tau-related insults, ischemia, traumatic brain injury), with a proposed mechanism centered on microtubule stabilization through interaction with end-binding (EB) proteins on growing microtubule plus-ends, particularly EB1 and EB3. The Oz 2014 work and follow-ons established the microtubule association reasonably cleanly. The microtubule stabilization story is mechanistically attractive because microtubule dysfunction is implicated in tau-related pathology.

Clinical development reached phase 2/3 for progressive supranuclear palsy (PSP), a tauopathy. The Boxer 2014 trial in PSP was the major readout and was disappointing: davunetide did not slow disease progression on primary endpoints. That ended the major commercial development push and significantly cooled enthusiasm for the compound. Subsequent trials in schizophrenia cognitive deficits and other indications have been small and largely uninformative.

The wrinkle is that the PSP trial design and the rate of progression in the placebo arm raised methodological questions about whether the trial was sensitive enough to detect the effect size you'd expect for a microtubule-stabilizing approach in late-stage tauopathy. The "negative trial doesnt mean negative drug" argument has plausibility here, though that's the kind of argument that gets made about every failed Alzheimer's program.

What we like: legitimate mechanism (microtubule stabilization through EB protein interaction), broad preclinical efficacy in neuroprotective contexts, an actual phase 3 trial that produced real safety data even if efficacy was disappointing. The mechanism is still scientifically interesting.

What we dont like is the unresolved post-trial trajectory. After the PSP failure, davunetide has been somewhat orphaned in the development pipeline, and the research peptide market picked it up as a "neuroprotective" peptide based largely on the preclinical claims rather than on the actual clinical data.

Sourcing: NAPVSIPQ is a short octapeptide, synthesis is straightforward, reputable peptide suppliers should deliver HPLC 98%+ purity reliably. Reconstitution is standard, storage is normal for short peptides. Quality issues are less common than for longer or more complex peptides.

Interesting microtubule biology, mixed clinical track record, the supplement-market positioning oversells where the human evidence sits.

Evidence: 50
Mechanism: 72
Reliability: 55
Safety: 75
Sourcing: 78
Value: 60
Signal: 55
Staying power: 55

Plain-language summary Intrigue 65 / 100

Davunetide (NAP) is an 8-amino-acid peptide derived from activity-dependent neuroprotective protein (ADNP). It supports microtubule integrity in neurons. Phase 2/3 trials in progressive supranuclear palsy were inconclusive. Not stocked by Kodiac. This monograph is provided for research and educational reference.

Intrigue 0–100 blends mechanism novelty, evidence strength, and translational potential. Kodiac editorial, not peer-reviewed.

ADNP-derived octapeptide

An eight-amino-acid fragment of activity-dependent neuroprotective protein (ADNP) studied in tauopathies and PSP.

Abstract

Davunetide (NAP, AL-108; Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln; CAS 173308-60-2; molecular weight 824.94) is an octapeptide derived from activity-dependent neuroprotective protein (ADNP). The peptide preserves microtubule integrity and reduces tau pathology in animal models of tauopathy. Davunetide was developed by Allon Therapeutics and advanced through Phase 2/3 trials in progressive supranuclear palsy (PSP); the pivotal trial in 2012 was negative for the primary cognitive endpoint, ending the development program. The compound is administered intranasally (the primary route of delivery to CNS for the formulation used in trials). Reported research dose ranges in the literature use intranasal milligram quantities.

Mechanism of action

Microtubule stabilization through ADNP-related mechanism; reduces tau pathology in tauopathy models.

Reported research dose ranges

Reported research dose ranges in the literature describe intranasal milligram quantities.

References

Boxer AL, et al. Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2/3 trial. Lancet Neurol 2014.

Read the full monograph

The full reference document covers compound identification, discovery and developmental history, mechanism of action, pharmacokinetics, reported research dose ranges, sourcing and quality verification, reconstitution and handling, stack interaction considerations, and a curated reference list. Available as a research-use-only PDF download.

KDC-MN-125

The full reference document is provided strictly for research use only. It reports research dose ranges from the published literature, not instructions for use in humans or animals.

Download PDF →

FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.

Kodiac sells research compounds for investigative use only.

Davunetide (NAP)

Abstract

Mechanism of action

Reported research dose ranges

References

Read the full monograph

Quick actions

Categories

Help and policies

Abstract

Mechanism of action

Reported research dose ranges

References

Read the full monograph

Adjacent monographs