spec sheet9 rows
R13 is a prodrug of 7,8-dihydroxyflavone, built by capping both of the parent compound's hydroxyl groups with carbamate esters so it survives the gut better. It was the one candidate out of twenty screened derivatives that made it through to animal work. It roughly doubles oral bioavailability and half-life compared with the parent, and in Alzheimer's model mice it reduced amyloid deposition, protected synapses and improved maze performance. ⚠️ Its mechanism inherits an argument. R13 is assumed to work by releasing 7,8-dihydroxyflavone, which is assumed to activate the TrkB receptor, and that second assumption is contested, with independent groups having failed to reproduce receptor activation.
- A genuine pharmacokinetic improvement over the parent compound, about double on bioavailability and half-life
- Reduced amyloid, protected synapses and improved maze performance in Alzheimer's model mice
- The nerve-regeneration result was reproduced by a group without the original senior author
- The only one of twenty screened derivatives to reach animal work
- No human exposure and no published toxicology
- The entire chronic safety record is one sentence about twelve weeks in mice, with no supporting data
- No selectivity screen against cholinesterases has been published, which carbamate chemistry invites
Mechanism
R13 is 7,8-dihydroxyflavone with both catechol hydroxyls masked as N-methylcarbamates. The masking is the point: those free hydroxyls are what make the parent compound get destroyed quickly, and capping them lets more of the molecule survive absorption before enzymes uncover it again.
The pharmacokinetics behave as a should [1]. In mice the parent compound given by mouth had 4.6 percent and a 134-minute ; R13 had about 10.5 percent and 219.6 minutes, with measurable brain exposure four hours after dosing.
Downstream, oral R13 activated signalling in brain tissue, blocked amyloid deposition, inhibited an enzyme that cleaves both APP and tau, reduced hippocampal loss and improved maze performance in a dose-dependent way.
⚠️ There is a specific gap in that chain worth naming. R13 was never tested against directly; the paper contains no binding assay and no cell-based receptor assay for the . All TrkB evidence is immunoblots of brain tissue after oral dosing, and the assumption is that R13 releases 7,8-dihydroxyflavone which then acts on the receptor.
⚠️ That second step is exactly the contested one. Direct agonism by 7,8-dihydroxyflavone has failed replication in independent laboratories using quantitative, orthogonal assays, including two industrial drug-discovery groups [4][5]. The downstream effects are reproducible; the receptor-level mechanism offered to explain them is not settled.
receptor fingerprint
7,8-dihydroxyflavone release ( conversion)Hydrolysed by liver and plasma enzymes
(NTRK2)Claimed activation, never tested directly
Delta-secretase (AEP) cleavage of APP and tauInhibits (downstream)
Evidencehow good the literature is
One primary paper plus two independent follow-ups on nerve regeneration.
The founding study screened twenty ester and carbamate derivatives, kept six that were stable in intestinal preparations and released the parent in liver preparations, and advanced this one alone to animal work [1]. In Alzheimer's model mice it improved maze performance dose-dependently and reduced amyloid and synapse loss.
⚠️ The replication picture is genuinely mixed, and the distinction matters. A study of nerve regeneration after sciatic nerve transection found a single oral dose produced prolonged TrkB and ERK signalling at the injury site, with better regeneration at four weeks than either vehicle or oral 7,8-dihydroxyflavone [2]; the originating senior author is a co-author on it. A follow-up from the same group showing improved muscle reinnervation does not include him [3], which makes it the most independent confirmation the compound has.
What is missing is any test of R13 itself against its supposed target, and any human exposure at all.
Dosingtypical ranges, not medical advice
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Safetyrisks and cautions, not medical advice
No human has taken it, and no formal toxicology has been published.
The source paper states that twelve weeks of daily dosing in mice showed no toxicity. ⚠️ That sentence is the entire chronic safety record: no supporting numbers, no tissue examination and no blood chemistry are given with it.
The carbamate chemistry is worth a note. Carbamates as a class can inhibit cholinesterases, and while nothing suggests this particular molecule does so meaningfully, no selectivity screen against those enzymes has been published either.
History
R13 came out of a 2018 effort to make 7,8-dihydroxyflavone usable by mouth, from the laboratory that has generated most of the positive primary data on that compound. Twenty derivatives were made and screened, and this one survived. It has since been picked up by nerve-regeneration researchers, where its most independent supporting data now sits, and it circulates in research-chemical channels on the strength of the Alzheimer's model results.
Resources
This entry is here for reference.
Research
- 2017first citedMultiplex quantitative assays indicate a need for reevaluating reported small-molecule TrkB ago…
- 2023most recentProportions of four distinct classes of sensory neurons are retained even when axon regeneratio…
- 1.The prodrug of 7,8-dihydroxyflavone development and therapeutic efficacy for treating Alzheimer's disease
- 2.Oral Treatments With the TrkB Ligand Prodrug, R13, Promote Enhanced Axon Regeneration Following Peripheral Nerve Injury
- 3.Proportions of four distinct classes of sensory neurons are retained even when axon regeneration is enhanced following peripheral nerve injury.
- 4.Multiplex quantitative assays indicate a need for reevaluating reported small-molecule TrkB agonists
- 5.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.
5 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
Is R13 better than plain 7,8-DHF?
On delivery, measurably yes: about double the oral bioavailability and double the half-life in mice, with brain exposure lasting longer. In a nerve regeneration study it also outperformed the parent given by the same route. Whether that translates into anything for a person is unknown, since nobody has taken it.
Does R13 activate TrkB?
Nobody has tested it directly. There is no binding assay and no cell assay for R13 itself; the evidence is that TrkB signalling rises in brain tissue after oral dosing, with the assumption that R13 releases 7,8-dihydroxyflavone which acts on the receptor. That second step is the one independent laboratories have failed to reproduce.
Limitations of the evidence
- R13 was never tested against TrkB directly; there is no binding assay and no cell assay for it
- Its mechanism depends on 7,8-dihydroxyflavone activating TrkB, which failed replication in two independent laboratories
- Most positive data comes from the laboratory that created it
- Bioavailability is still only about 10 percent even after the improvement
- Its structure-to-code assignment comes from a commercial catalogue rather than the primary paper
Adverse effects
- No human exposure and no published toxicology
- The entire chronic safety record is one sentence about twelve weeks in mice, with no supporting data
- No selectivity screen against cholinesterases has been published, which carbamate chemistry invites