Back to Registry

Dihexa

Also known as: N-Hexanoyl-Tyr-Ile-(6)-amino hexanoic amide, PNB-0408

Research Only

Molecular Formula

C27 H44 N4 O5

Molecular Weight

504.66 Da

Half-Life

Unknown in humans (~12.7 days IV / ~8.8 days IP estimated in small rat cohorts; cursory data under Expression of Concern)

Sequence

N-hexanoyl-YI-Ahx-NH2

Clinical Applications & Evidence

Mechanism of Action

Proposed in rodent models to interact with the hepatocyte growth factor (HGF)/c-Met axis, activating downstream PI3K/AKT signaling to promote dendritic spinogenesis and synaptogenesis. However, the 2014 paper reporting high-affinity picomolar binding (Kd ~65 pM) and HGF dimerization modulation was retracted in 2025. Independent rodent studies (2021 APP/PS1 mouse model, 2025 rat TBI model) support involvement in neural signaling cascades, but human pharmacological mechanisms remain unvalidated.

Investigated Uses

  • Alzheimer's disease models (Preclinical — APP/PS1 & scopolamine rodent models only)
  • Age-related cognitive impairment (Preclinical rodent models)
  • Traumatic brain injury recovery (Preclinical — 2025 rat TBI study)
  • Synaptogenesis & neuroplasticity (Preclinical cell & animal models)
Animal Models Only

Regulatory & Safety Status

FDA Status

Research Only

WADA / Athletic Status

Prohibited at All Times (WADA S4.4.1)

Known Side Effects

No controlled human adverse-event dataset availableAnecdotal self-reports (headache, overstimulation) are unverified

Contraindications

  • Theoretical oncologic risk (HGF/c-Met activation plays a known role in tumor cell proliferation and angiogenesis)
  • WADA-tested athletes (Prohibited at all times under S2.3 Growth Factor Modulators / S0 Unapproved Substances)
  • Pregnancy and breastfeeding (Unstudied; unknown safety profile)

Drug Interactions

  • Unknown in humans — no formal pharmacokinetic or drug interaction studies exist

Citations & Clinical Trials

PubMed Evaluation of Angiotensin IV-Derived Peptides in Animal Models (Expression of Concern 2023) PubMed Retraction RETRACTED (2025): The Transmembrane Domain of HGF Dimerization & Dihexa Binding PubMed Dihexa Ameliorates Cognitive Deficits in APP/PS1 Transgenic Mice (2021) SAGE Journals Effects of Dihexa in a Rat Model of Repeated Mild Traumatic Brain Injury (2025)