P-21

Designed by Khalid Iqbal's group at the New York State Institute for Basic Research. It copies a short active piece of ciliary neurotrophic factor (CNTF), a natural brain-support protein, and adds an adamantane group to survive digestion and reach the brain.

Proposed from rodent work: it blocks leukemia inhibitory factor (LIF) signaling, raises brain-derived neurotrophic factor (BDNF) and phosphorylated CREB, and lowers activity of GSK-3β, an enzyme that adds phosphate groups to tau. Treated animals showed more new-neuron markers in the hippocampus and better synaptic protein levels.

Fed to mice and rats, P-21 increased new-neuron formation and improved memory in models of aging, Alzheimer's disease and Down syndrome. In a Down syndrome mouse model, treatment through the mother's diet rescued developmental delay and adult memory deficits; in female Alzheimer's-model mice, long-term treatment improved maze performance, though some synaptic results were only trends and groups were small. No human trial, pharmacokinetic study or case series exists, and the work has not been independently replicated outside the originating lab.

Side effects in people are unknown; there is no formal toxicology and no human safety data. Because it is designed to promote cell growth and survival, long-term cancer risk is an unstudied theoretical concern.

Not FDA-approved for any use, and no IND or clinical trial was found. Not eligible for compounding (not on FDA's 503A nominations or safety-risk lists). Not named on the 2026 WADA list; as an unapproved substance it would fall under S0.