P21 (P021)

P21, written P021 in most of the primary literature, is a synthetic peptidomimetic derived from ciliary neurotrophic factor (CNTF). Its formula is C27H42N6O8, its molecular weight 578.7 g/mol, its CAS number 1246751-68-7 and its PubChem CID 56599151. It is a four-residue acetylated chain, Asp-Gly-Gly-Leu, capped with a non-standard adamantylated glycine amide, written Ac-DGGL-Ag. Adamantane is a rigid cage-shaped hydrocarbon, added to raise lipophilicity and resistance to peptidase cleavage; that synthetic residue is why the literature calls this a mimetic, not a peptide fragment.

One point of confusion outranks the rest. The name p21 also belongs to a well known human protein, the cyclin-dependent kinase inhibitor encoded by the gene CDKN1A and written p21WAF1/Cip1. That protein is a 164-residue cell-cycle regulator with a large literature of its own on senescence and tumour suppression. It is a different molecule, and none of the CDKN1A literature describes the compound on this page. Searches for “p21” return the protein first, so P021 is the safer search term.

P021 came from the Iqbal and Grundke-Iqbal programme at the New York State Institute for Basic Research in Developmental Disabilities, Staten Island. The starting point was Peptide 6, an 11-residue sequence designed from an active region of CNTF (PubMed 19767127). Li and colleagues reported the shortened adamantylated derivative P021 in 2010 (PubMed 20600002).

The in vivo record is mostly rodent. Kazim and colleagues investigated P021 in a triple transgenic mouse model of Alzheimer-type pathology (PubMed 25046994) and in the Ts65Dn model of Down syndrome (PubMed 28368015). An independent Bologna group investigated it in CDKL5 deficiency models (PubMed 39592934).

The evidence base is preclinical, narrow and dominated by the originating laboratory, with no published or registered human trial. The wider CNTF-derived peptide literature is partly compromised: a 2011 report comparing Peptides 6 and 6A with cerebrolysin was retracted in June 2026 and is excluded here (PubMed 21860085, notice PubMed 42015030). Every reference below was checked against PubMed retraction and expression-of-concern records; none carries either.

The mechanism most often attributed to P021 is indirect neurotrophic signalling. Published work reports raised brain-derived neurotrophic factor expression in rodent studies, with the parent Peptide 6 described as a competitive inhibitor of leukemia inhibitory factor signalling (PubMed 20600002, PubMed 25046994). No direct binding partner for P021 has been established, so this is a proposed route, not a mapped one.

Two distinctions are worth holding. The first is the CDKN1A protein described above: results reported for it do not transfer here. The second is Dihexa, the other designed mimetic here. Both are short capped molecules built to imitate a natural ligand, but their parents differ: angiotensin IV and hepatocyte growth factor signalling for Dihexa, CNTF and BDNF-linked signalling here.

A methodology caveat applies. Almost all reported effects come from rodent behavioural paradigms, immunohistochemical cell counts and tissue protein measurements, so a finding belongs to the assay that produced it. Group sizes are small and several studies share authors and models.

Sealed lyophilized P021 is stored frozen at -20°C, shielded from light, in its original container. Lyophilized means freeze-dried, and such material is hygroscopic, so a container reaches ambient temperature before opening.

Repeated freeze-thaw cycles are avoided. No duration is asserted here: stability for a lot is documented on its Certificate of Analysis (COA).

Reconstitution means returning a lyophilized compound to solution. No preparation procedure appears here: solvent and concentration belong to a study protocol, read alongside the lot COA.

Solubility here is mixed rather than simply aqueous. The aspartate side chain and terminal carboxamide are polar while the adamantyl cage is strongly hydrophobic, so it behaves unlike an ordinary short peptide on a column or in buffer.

Identity and purity are established by reverse-phase high-performance liquid chromatography and by mass spectrometry, the primary check being an observed mass consistent with 578.7 g/mol. Verified purity is documented per lot on the COA.

Two quality points are specific to this molecule. The adamantylated residue is non-standard, so a truncated chain missing that cap is detectable by mass. Deamidation is the classic degradation route for Asp-Gly sequences and shifts mass only slightly; observed mass is read against the stated salt form.

P21 sits with compounds studied in central nervous system models:

• Dihexa.
  An angiotensin IV derived peptidomimetic, the closest parallel as a designed mimetic.
• DSIP.
  A natural nonapeptide with a disputed endogenous role, the opposite case to a built mimetic.
• Semax.
  A synthetic ACTH(4-10) analogue studied in rodent central nervous system models.
• Selank.
  A tuftsin analogue investigated in animal models of anxiety-related behaviour.

Chohan MO, Li B, Blanchard J, et al. (2011). Enhancement of dentate gyrus neurogenesis and memory by a neurotrophic peptide. Neurobiol Aging.
PubMed 19767127

Li B, Wanka L, Blanchard J, et al. (2010). Neurotrophic peptides incorporating adamantane improve memory in mice. FEBS Lett.
PubMed 20600002

Kazim SF, Blanchard J, Dai CL, et al. (2014). Disease modifying effect of a neurotrophic peptidergic compound in mice. Neurobiol Dis.
PubMed 25046994

Kazim SF, Blanchard J, Bianchi R, Iqbal K (2017). Early neurotrophic pharmacotherapy in the Ts65Dn mouse model. Sci Rep.
PubMed 28368015

Mottolese N, Loi M, Trazzi S, et al. (2024). Effects of a CNTF peptide mimetic in models of CDKL5 deficiency disorder. J Neurodev Disord.
PubMed 39592934

Rockenstein E, Ubhi K, Doppler E, et al. (2011). Regional comparison of the neurogenic effects of CNTF-derived peptides and cerebrolysin in AbetaPP transgenic mice. J Alzheimers Dis. PubMed 21860085 (retracted in 2026; listed only to record the exclusion)
PubMed 21860085

Retraction notice (2026). Retraction: Regional Comparison of the Neurogenic Effects of CNTF-Derived Peptides and Cerebrolysin in AbetaPP Transgenic Mice. J Alzheimers Dis. PubMed 42015030
PubMed 42015030

Peptides.com lists two P21 research products, both sealed lyophilized vials, from Real Peptides and Verified Peptides. They are listed at 5mg and 10mg, and those per-vial strengths are product specifications, not research quantities. Vials are the only listed format. Each lot is supplied with a published Certificate of Analysis documenting verified purity and identity.

• Browse all P21 research products
• Real Peptides P21, 5mg lyophilized vial
• Verified Peptides P21, 10mg lyophilized vial

These products are sold for Research Use Only and are not intended for human consumption.