P-21

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What P-21 is

P-21, written P021 or Peptide 021 in most of the literature, is a synthetic peptidomimetic from Khalid Iqbal's laboratory at the New York State Institute for Basic Research in Developmental Disabilities. Li and colleagues first reported it in FEBS Letters in 2010, under the spelling P21 and the sequence Ac-DGGLAG-NH2, in which the A before the final G marks an adamantylated glycine, not alanine. It is catalogued under Nootropic and Neurological.

How it was built from CNTF

The group's 2016 review in Molecular Neurodegeneration (Kazim and Iqbal) says the clinical use of ciliary neurotrophic factor (CNTF), a full-length protein, is restricted by a short plasma half-life and by adverse effects in people, including anorexia, skeletal muscle loss and hyperalgesia. The review traces P-21 through three steps:

• Peptide 6: an 11-residue fragment, Ac-VGDGGLFEKKL-NH2, matching residues 146 to 156 of human CNTF and identified by epitope mapping with neutralizing antibodies.
• Peptide 6c: the four-residue core Ac-DGGL-NH2, which the group reports kept neurogenic activity.
• P021: Peptide 6c with an adamantylated glycine added to enhance blood-brain-barrier permeability.

The group's 2017 Scientific Reports paper places that core at residues 148 to 151 of human CNTF. The 2016 review calls P-21 a pentamer, while a 2024 paper and one vendor description call it a tetrapeptide, counting only the CNTF residues.

The developers report that P-21 competitively inhibits leukemia inhibitory factor (LIF) signalling at the LIF/CNTF receptor, measured as lower STAT3 phosphorylation.

What the animal studies tested

All of the work below is in mice or cultured cells, and Iqbal is an author on every paper.

• Normal mice (2010): in adult C57Bl6 mice, it enhanced learning and short-term and spatial reference memory, and increased neurogenesis and maturation of new neurons in the dentate gyrus (Li, FEBS Letters, 2010).
• Alzheimer's model (2014): female 3xTg-AD mice received P021 in their diet for 12 months from 9 to 10 months of age. It reduced tau hyperphosphorylation and accumulation, lowered soluble amyloid-beta with only a trend toward less plaque in the CA1 region, raised BDNF expression and lowered GSK-3β activity, the pathway the authors propose for those changes, and rescued deficits in cognition, neurogenesis and synaptic plasticity (Kazim, Neurobiology of Disease, 2014).
• Down syndrome model (2017): treating Ts65Dn mothers from the eighth day of pregnancy until weaning rescued developmental delay in the pups and hippocampus-dependent memory deficits in adulthood, with higher BDNF and phosphorylated CREB at 3 weeks and about 7 months (Kazim, Scientific Reports, 2017).
• CDKL5 deficiency model (2024): a University of Bologna group found it restored proliferation, survival and maturation in a human neuronal cell line lacking CDKL5, but in Cdkl5 knockout mice it did not raise BDNF or correct neuroanatomical defects, and catalepsy was the only behavioural deficit it restored (Mottolese, Journal of Neurodevelopmental Disorders, 2024).

Two earlier papers from the laboratory, a 2010 study in 3xTg-AD mice (Acta Neuropathologica) and a 2011 study in Ts65Dn mice, tested the parent Peptide 6, not P-21.

Human data and developer interests

ClinicalTrials.gov lists no study of P-21 as of October 2026, and a Europe PMC search for P021 returned only animal, cell and review papers. The 2024 paper's competing-interest statement says Iqbal co-founded Phanes Biotech, holds several patents on the composition and use of P021, and was developing it as a drug for Alzheimer's disease and related disorders.

Vendor naming and the p21 search problem

• Vendor titles write P21, the 2010 paper's spelling, with a vial size or count.
• One vendor description calls it Peptide 021, and another prints Ac-DGGL(A)G-NH2, where (A)G marks the adamantylated glycine.
• One supplier compares its Adamax to P-21, but Adamax is a separate product and none of the studies above tested it.
• P21 is also an alias of p21, the cyclin-dependent kinase inhibitor encoded by the human gene CDKN1A (NCBI Gene also lists CIP1, WAF1 and p21CIP1), an unrelated protein, so a literature search on P21 mixes the two and the developers' spelling, P021, is more specific.

Regulatory status

PeptideScouter found no US approval, compounding nomination, trial or enforcement record for P-21. As of October 22, 2026, it appears in none of these:

• FDA's Drugs@FDA database of approved and tentatively approved applications
• Either table of FDA's Category 2 list of bulk substances raising significant safety risks (page current as of April 22, 2026)
• FDA's list of bulk substances nominated under Section 503A (updated May 14, 2026) or Section 503B (updated March 21, 2025)
• The substances FDA named for its July 2026 Pharmacy Compounding Advisory Committee meeting or for its next one, due before the end of February 2027
• ClinicalTrials.gov, searched as P021, P-21, Peptide 021 and CNTF peptide (its CNTF results concern other products, such as an implant that releases CNTF itself)
• FDA's warning-letter database

The one FDA record found is an entry in its substance registry, GSRS, created in August 2026 under the name P-21 with the identifier UNII VV8CZC8PAS.

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