spec sheet8 rows
P7C3-A20 is the most-used member of the P7C3 family of aminopropyl carbazoles, a series that protects neurons in a striking range of animal injury models: traumatic brain injury, stroke, Parkinson's models, nerve injury and more. ⚠️ Its mechanism is described everywhere as activation of NAMPT, the enzyme that limits NAD regeneration. No binding or potency constant at that enzyme has ever been published for it, and the originating laboratory now describes the series as NAD-stabilising rather than NAMPT-activating. ⚠️ The only fully independent laboratory test of it in culture was negative twice: it failed to protect neurons in three separate systems, and it was toxic at higher concentrations.
- Protection across an unusually wide range of brain injury models, from several laboratories
- Worked in mice when treatment began a full year after traumatic brain injury
- Selected on a living-animal phenotype rather than a target, which is a demanding way to find a molecule
- Concentration-dependent neurotoxicity in the one independent culture study
- No human safety data, toxicology or pharmacokinetics of any kind
Mechanism
The proposed mechanism is support of NAD metabolism. NAD is consumed continuously and regenerated from nicotinamide by NAMPT, the rate-limiting enzyme in that salvage route, and the series is said to increase that enzyme's activity and so keep NAD levels up in stressed neurons [2].
⚠️ That claim has never been quantified. No Kd, Ki, EC50 or IC50 at NAMPT has been published for this compound or any other member of the series, in the founding paper or in the fifteen years since. The evidence offered was competition against a photo-crosslinking probe and activation of recombinant enzyme at 10 micromolar with no constant reported. The two NAMPT activators that have been structurally characterised bind a site called the rear channel [8]; no such binding has been demonstrated for this compound, and the originating laboratory now writes that the series stabilises NAD rather than that it activates the enzyme.
⚠️ The NAD effect is also conditional. The founding work reported no compound-mediated change in NAD levels in untreated cells; the effect appears in cells that have been depleted. Raised NAD has been measured in animal tissue, but that is a downstream reading rather than evidence of what the molecule binds.
⚠️ The -1 receptor mechanism belongs to a different compound. modulation of that receptor was shown for the prototype P7C3 [7], and the source paper states that this compound and its sibling do not engage that pathway. It should not be carried across.
⚠️ The one measured protein affinity in the whole series is an off-target, at TSPO, and it belongs to the sibling compound rather than this one.
receptor fingerprint
Neuronal apoptosis after injuryReduces
Hippocampal Increases survival of new neurons
NAMPT / NAD salvageClaimed activator; no constant ever measured
-1 receptorNot engaged by this compound
Evidencehow good the literature is
A wide and consistent animal literature, and one negative independent replication in culture.
The strongest single result is a study where treatment began a year after traumatic brain injury in mice and still repaired the blood-brain barrier, halted ongoing degeneration and restored cognition [5]. Protection has also been reported in ischaemic stroke [4] and after intracerebral haemorrhage, where the effect tracked an NAD and sirtuin pathway [6].
⚠️ The one fully independent in-vitro replication attempt failed. Across dissociated cortical neurons, dissociated ganglion neurons and ganglion explants, the compound gave no protection against degeneration induced either by cutting the neurite or by vincristine, and produced concentration-dependent neurotoxicity [3].
⚠️ Two commonly repeated claims could not be traced to a primary source. A 2023 review refers to safety and efficacy in non-human primates [9] without a primary publication that could be located, and reports of commercial development appear only in web coverage with no regulatory filing or trial registration behind them.
⚠️ There are zero registered clinical trials, fifteen years after the series was discovered.
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. There is no human safety data, no toxicology and no pharmacokinetics.
⚠️ The one independent in-culture study of it reported concentration-dependent neurotoxicity alongside its failure to protect [3]. That is the only laboratory outside the originating group to have tested it this way, and both of its findings were unfavourable. Nothing published since has resolved the discrepancy between that result and the animal literature.
Animal studies at their working doses report no obvious toxicity, but none was designed as a safety study.
History
The series came out of a 2011 screen for molecules that increased the survival of newborn neurons in living mice, an unusual approach that started from an in vivo phenotype rather than a target [1]. The target was proposed three years later. Chemical optimisation produced this compound as the workhorse analogue, and a large animal literature followed across many injury models and several laboratories.
What has not followed is a clinical programme. No trial has been registered, and the mechanistic account has quietly softened over the same period from enzyme activation to NAD stabilisation.
Resources
This entry is here for reference.
Research
- 2011first citedDevelopment of proneurogenic, neuroprotective small molecules
- 2023most recentApplication of P7C3 Compounds to Investigating and Treating Acute and Chronic Traumatic Brain I…
- 1.Development of proneurogenic, neuroprotective small molecules
- 2.P7C3 neuroprotective chemicals function by activating the rate-limiting enzyme in NAD salvage
- 3.P7C3-A20 neuroprotection is independent of Wallerian degeneration in primary neuronal culture
- 4.Neuroprotective Efficacy of an Aminopropyl Carbazole Derivative P7C3-A20 in Ischemic Stroke
- 5.P7C3-A20 treatment one year after TBI in mice repairs the blood-brain barrier, arrests chronic neurodegeneration, and restores cognition
- 6.P7C3-A20 Attenuates Microglial Inflammation and Brain Injury after ICH through Activating the NAD(+)/Sirt3 Pathway
- 7.GSK-3 inhibition through GLP-1R allosteric activation mediates the neurogenesis promoting effect of P7C3 after cerebral ischemic/reperfusional injury in mice
- 8.Synthesis, Optimization, and Structure-Activity Relationships of Nicotinamide Phosphoribosyltransferase (NAMPT) Positive Allosteric Modulators (N-PAMs)
- 9.Application of P7C3 Compounds to Investigating and Treating Acute and Chronic Traumatic Brain Injury
9 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
Does P7C3-A20 activate NAMPT?
Nobody has measured it. No binding or potency constant at that enzyme exists for this compound or any other in the series, in the founding paper or since. The supporting evidence was competition against a chemical probe and activation of recombinant enzyme at a single high concentration. The laboratory that made the original claim now describes the series as stabilising NAD rather than activating the enzyme.
Is it the same as P7C3 or P7C3-S243?
No. They have different registry numbers, different formulae, different linker chemistry and a different ring on one end, and this one is a racemic mixture while S243 is a single purified enantiomer. Most usefully, the prototype P7C3 works partly through the GLP-1 receptor and its own source paper says this compound does not.
Why does this entry mention toxicity when everything else calls it neuroprotective?
Because the only laboratory outside the originating group to test it in culture reported concentration-dependent neurotoxicity, alongside a complete failure to protect neurons in three separate systems. That result has never been resolved against the animal literature, and leaving it out would make the picture look settled when it is not.
Limitations of the evidence
- No binding or potency constant at NAMPT has ever been published for any compound in this series
- The originating laboratory now describes the series as NAD-stabilising rather than NAMPT-activating
- NAD only rises in depleted cells; the founding paper reported no effect in untreated ones
- The only fully independent in-culture replication found no protection in three systems
- Zero registered clinical trials fifteen years after discovery
- Claims of non-human primate safety data trace to a review with no locatable primary source
- Not interchangeable with P7C3 or P7C3-S243; different chemistry, and it does not share the prototype's GLP-1 receptor mechanism
Adverse effects
- Concentration-dependent neurotoxicity in the one independent culture study
- No human safety data, toxicology or pharmacokinetics of any kind