From a preclinical breakthrough in mice to the AI tools that could bridge the gap to human therapies. Rigorous science, openly shared.
Understanding the metabolic coenzyme at the center of the Alzheimer's reversal breakthrough.
NAD+ (nicotinamide adenine dinucleotide) is a coenzyme found in every cell of your body. Think of it as molecular fuel. It plays a critical role in energy metabolism, DNA repair, and cellular signaling. Without it, cells can't function. With declining levels, they deteriorate.
As we age, NAD+ levels drop -- sometimes by as much as 50% by age 60. This decline is linked to nearly every age-related disease, including Alzheimer's. The brain, one of the most energy-hungry organs, is especially vulnerable.
NAD+ powers the creation of new mitochondria, the energy factories inside neurons
NAD+ activates sirtuins and PARP enzymes responsible for repairing damaged DNA
Over-the-counter NMN/NR supplements boost NAD+ modestly. P7C3-A20 activates the NAD+ salvage pathway at NAMPT, the rate-limiting enzyme, achieving far greater efficacy
P7C3-A20 reversed amyloid plaque accumulation, resolved tau tangles, repaired the blood-brain barrier, and restored cognitive function in 5xFAD mice -- the most aggressive Alzheimer's mouse model. DOI: 10.1016/j.xcrm.2025.102535
The Cell Reports Medicine paper revealed multiple mechanisms. NAD+ is just the beginning.
P7C3-A20 was shown to upregulate the IDOL enzyme (Inducible Degrader of the LDL Receptor), which plays a role in cholesterol metabolism and lipid raft dynamics in the brain. Disrupted cholesterol metabolism is increasingly recognized as a driver of Alzheimer's pathology.
The compound corrected aberrant RNA splicing patterns in Alzheimer's neurons. Mis-spliced RNA produces dysfunctional proteins that contribute to neurodegeneration. Restoring proper splicing is a novel therapeutic angle that most drug programs overlook.
Restored microglial phagocytosis, allowing the brain's immune cells to clear amyloid plaques
Reduced hyperphosphorylated tau, the protein tangles that destroy neuronal connectivity
Decreased activation of inflammatory pathways (NF-kB, TNF-alpha) in brain tissue
The gap between breakthrough and therapy is not just biological. It's economic.
Most academic labs investigating Alzheimer's cannot afford commercial computational platforms. Schrodinger costs $500,000+ per year. MOE, Desmond, and other industry-standard tools carry similar price tags. This means the vast majority of Alzheimer's researchers are locked out of the computational tools that could accelerate their work.
37+ modules covering virtual screening, molecular docking, protein structure prediction, de novo design, MD simulation, toxicology, and stability prediction. Runs on standard hardware -- no supercomputer required.
While our tools are computational, several clinical trials are exploring NAD+-related compounds in humans:
| Trial ID | Compound | Phase | Status |
|---|---|---|---|
| NCT05483465 | Nicotinamide Riboside (NR) | Phase II | Active |
| BenfoTeam | Benfotiamine | Phase II | Recruiting |
| NCT07127510 | NAD+ Precursor Combination | Phase I | Planned |
Honest disclaimer: The P7C3-A20 findings are a preclinical breakthrough in mice. This has not yet been proven in humans. The path from mouse model to human therapy is long and uncertain. Our AI tools accelerate the computational phase, but clinical trials and regulatory approval remain essential steps.
37+ modules for computational drug discovery. Free for researchers.