spec sheet8 rows
7,8,3'-Trihydroxyflavone is a close relative of 7,8-dihydroxyflavone with one extra hydroxyl, reported in the founding work on that compound to produce an even stronger effect on TrkB signalling. ⚠️ It has no measured binding affinity at TrkB. No Ki, Kd, IC50 or EC50 from a binding assay has ever been published for it, and the potency figures that circulate are fold-changes in signalling readouts, which are not measurements of target engagement. ⚠️ It was one of the compounds tested directly in an independent replication attempt, and it was inactive.
- Reported stronger TrkB signalling effects than its better-known relative
- Reproducible downstream effects on neurite outgrowth and oxidative stress
- No safety data, toxicology or human exposure of any kind
Mechanism
The compound is a flavone with hydroxyls at the 7, 8 and 3' positions, one more than 7,8-dihydroxyflavone. The founding structure-activity work on that series reported that adding the 3' hydroxyl produced a stronger stimulatory effect on phosphorylation and on downstream signalling [1].
⚠️ No binding measurement exists. There is no published dissociation constant, inhibition constant or half-maximal concentration from any binding assay for this compound at . The numbers people quote as potency are fold-changes in phospho-protein readouts, which describe a downstream consequence rather than an interaction with the receptor.
Downstream effects reported for it include neurite outgrowth, protection against and reduced inflammatory signalling in cell and animal models [3].
⚠️ The whole class this belongs to rests on a contested claim. Nearly all the positive primary data for direct activation of by small molecules comes from one research group, and at least three independent teams have failed to reproduce receptor-level activation. Two of those were industrial drug-discovery groups using quantitative assays with a monoclonal antibody as a positive control [6][7], and a later review reached the same conclusion [8]. Downstream biological effects are often reproducible; the step in dispute is whether they happen by binding the receptor.
receptor fingerprint
(NTRK2) receptorClaimed agonist; no affinity ever measured
Neurite outgrowth and Improves (downstream)
Evidencehow good the literature is
A small scattered literature, and one direct comparison that went badly for it.
⚠️ The most informative study gave it alongside BDNF in deafened guinea pigs and found BDNF better at preserving the auditory nerve [2]. The paper's own framing is that the small molecule underperformed the protein it is meant to substitute for.
Other work reports neurite regeneration and reduced oxidative stress [3], and it appears in cochlear explant and neuroinflammation models [4][5]. These are downstream readouts rather than receptor measurements.
⚠️ No trial has ever been registered for this compound, and no human pharmacokinetic, safety or efficacy data exists.
Dosingtypical ranges, not medical advice
interested in protocols and clinical dosages? make an account to see them! ^_^
Safetyrisks and cautions, not medical advice
No human has taken it in any published study, and no toxicology exists.
As a catechol-bearing flavone it would be expected to be poorly absorbed and rapidly conjugated, the same limitation that motivated the prodrug work on its parent compound, but no pharmacokinetic study of this molecule has been published in any species.
History
The compound appeared in the 2010 structure-activity work that introduced 7,8-dihydroxyflavone as a proposed TrkB agonist, where the extra hydroxyl was reported to strengthen the effect. It has since been used occasionally as a research tool, mostly in hearing and nerve regeneration models, and has never been developed.
Subjective profileweighing the evidence above
Not worth taking, and the reason is unusually direct rather than merely absent evidence. ⚠️ In a head-to-head study in deafened guinea pigs, BDNF itself outperformed this compound at preserving the auditory nerve, and that comparison is the title of the paper [2]. A molecule sold as a BDNF mimic being beaten by BDNF in a direct test is the single most useful thing to know about it. ⚠️ It was also among the compounds an independent group tested when reevaluating the class, and it did not show the receptor activation claimed for it. There is no human data of any kind: no trial, no sponsor, no pharmacokinetics, no safety study.
Resources
This entry is here for reference.
Research
- 2010first citedA selective TrkB agonist with potent neurotrophic activities by 7,8-dihydroxyflavone
- 2020most active year3 papers
- 2021most recentDo Small Molecules Activate the TrkB Receptor in the Same Manner as BDNF? Limitations of Publis…
- 1.A selective TrkB agonist with potent neurotrophic activities by 7,8-dihydroxyflavone
- 2.BDNF Outperforms TrkB Agonist 7,8,3'-THF in Preserving the Auditory Nerve in Deafened Guinea Pigs
- 3.7,8,3'-Trihydroxyflavone ameliorate oxidative stress in vivo and promotes neurite regeneration in vitro in rat retinal ganglion cells.
- 4.Age-Dependency of Neurite Outgrowth in Postnatal Mouse Cochlear Spiral Ganglion Explants
- 5.Characterising lipoteichoic acid as an in vitro model of acute neuroinflammation
- 6.A monoclonal antibody TrkB receptor agonist as a potential therapeutic for Huntington's disease
- 7.Multiplex quantitative assays indicate a need for reevaluating reported small-molecule TrkB agonists
- 8.Do Small Molecules Activate the TrkB Receptor in the Same Manner as BDNF? Limitations of Published TrkB Low Molecular Agonists and Screening for Novel TrkB Orthosteric Agonists.
8 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
Is it stronger than 7,8-DHF?
That claim comes from the original structure-activity work, which reported a bigger effect on TrkB phosphorylation from the extra hydroxyl. It is a comparison of signalling readouts, not of binding, and neither compound has a binding constant behind it. In the one head-to-head against BDNF itself, this compound came off worse.
Limitations of the evidence
- No binding constant of any kind has ever been measured for it at TrkB
- BDNF outperformed it in a direct head-to-head comparison in deafened guinea pigs
- It was among the compounds an independent group found inactive when reevaluating the class
- No pharmacokinetic data in any species, and no registered trial
- The circulating potency figures are signalling fold-changes, not target engagement
Adverse effects
- No safety data, toxicology or human exposure of any kind