I’m doing research almost every day and this the most exciting molecule I have come across in a while. Phase I trial (jRCT2031210495) in Japan has been completed, confirming its safety and pharmacokinetics in healthy subjects with 40mg being tested as the highest dose.
I will be getting some made, specifically the S enantiomer and would like to do a group buy if anyone is interested. I am waiting to hear back on quotes.
I will be deep diving into all the papers on it this week. One paper shows that “MA-5 ameliorates autism-like behavior in mice prenatally exposed to valproic acid”
Link below is a good summary of its anti aging benefits.
https://doi.org/10.1101/2025.04.18.649305
Here is an AI summary of the linked paper:
- Clinical status
MA-5’s racemate has completed a Phase I trial in Japan (jRCT2031210495) and received PMDA approval to enter Phase II .
- Multifaceted “anti-aging” triad
MA-5 engages three complementary, non–DNA-damaging pathways that counter hallmarks of aging:
ATP enhancement
– Binds mitochondrial mitofilin to elevate ATP production in diseased fibroblasts and ex vivo cochlea .
NAD⁺ up-regulation via NAMPT activation
– The S-enantiomer allosterically activates NAMPT (EC₅₀ in the nM range), raising NAD⁺ more potently than the racemate; this drives sirtuin co-factor availability .
Sirtuin protein stabilization through DNA-PK → TRIM28
– S-enantiomer triggers DNA-PKcs autophosphorylation (Ser2056), which phosphorylates TRIM28 (Ser824). This blocks SIRT1–7 polyubiquitination, boosting all seven sirtuin proteins—a first reported non-transcriptional up-regulation of the family .
Transcriptomic signatures after MA-5 treatment in mice mirror “rejuvenation” profiles (OSKM/iPSC) and inversely correlate with aging- and mortality-associated gene sets .
Put simply, when researchers looked at which genes were switched on or off in mice treated with MA-5, they found two key things:
It made the mice’s cells behave more “youthful."
The overall pattern of gene activity closely resembled what you see when mature cells are reset toward a stem-cell–like, rejuvenated state (the same sort of signature you get after applying the famous “Yamanaka factors” used to create induced pluripotent stem cells).
It pushed their cells away from an “old” profile.
Those same genes that normally change in older or unhealthy animals—genes linked to age-related decline or even higher risk of death—were altered in the opposite direction. In other words, MA-5 flipped on the “young” switches and flipped off the “aging” ones.
- Hearing-loss reversal
In four mouse models—genetic (Ndufs4 KO, age-related), noise-induced, and cisplatin-induced—oral MA-5 (1–10 µg/kg) significantly restored auditory thresholds (up to 10–20 dB improvements), rescued spiral-ganglion and hair-cell survival, and improved ABR even after hearing decline onset . Ex vivo, MA-5 elevates cochlear ATP and protects organ-of-Corti cells from ototoxins . In Leigh-syndrome patient fibroblasts, MA-5 also boosts ATP and survival under oxidative stress .
- Lifespan benefit
In the Ndufs4 KO mitochondrial disease mouse, chronic MA-5 dosing increased body weight and significantly prolonged survival versus controls .
Bottom line
MA-5’s coordinated enhancement of ATP, NAD⁺/sirtuins, and DNA-PK/TRIM28 creates a novel “anti-aging triad.” The S-enantiomer is the more desirable clinical candidate for maximizing NAD⁺ and sirtuin activation, and the racemate is already advancing through Phase II trials. Its robust reversal of multiple forms of hearing loss further underscores its translational potential.