Description:
HIFN (2-fluoro-N-(2-(5-hydroxy-1H-indol-3-yl)ethyl)nicotinamide) is a synthetic small-molecule agonist of the tropomyosin-related kinase B (TrkB) receptor, designed to mimic brain-derived neurotrophic factor (BDNF) signaling. Structurally, HIFN replaces the six-membered lactam ring of its parent compound HIOC with a fluoropyridine moiety, rendering it achiral and configurationally stable. This modification enhances binding affinity and pharmacokinetic properties.
HIFN activates TrkB by inducing receptor dimerization and phosphorylation, triggering downstream survival pathways (PI3K/Akt, MAPK/Erk). In vitro, HIFN outperforms HIOC in TrkB activation (10 nM concentration) in primary neurons and NIH-3T3-TrkB cells. In vivo, systemic administration of HIFN (30–40 mg/kg) mitigates blast-induced retinal ganglion cell (RGC) degeneration and preserves visual function (contrast sensitivity, acuity) in mice for up to 8 weeks post-injury. Its effects are TrkB-dependent, as co-treatment with the TrkB antagonist ANA-12 abolishes neuroprotection.
HIFN exhibits a critical therapeutic window of ≤3 hours post-injury and dose-dependent efficacy, with no toxicity observed at 600 mg/kg (acute) or 40 mg/kg/day (40-day chronic). Safety assessments reveal no histopathological or biochemical abnormalities in vital organs.
By combining potent TrkB activation, blood-retina barrier penetration, and a robust safety profile, HIFN emerges as a promising therapeutic candidate for traumatic optic neuropathy and broader CNS disorders involving TrkB dysregulation.
Handling:
Providing storage is as stated on the product vial and the vial is kept tightly sealed, the product can be stored for up to 24 months.
Wherever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance,
we recommend that you store the solution as aliquots in tightly sealed vials at -20°C. Generally, these will be useable for up to one
month. Before use, and prior to opening the vial we recommend that you allow your product to equilibrate to room temperature for at
least 1 hour.