Informational only. Not medical advice.INFORMATIONAL PLATFORM ONLY — NOT MEDICAL ADVICE, DIAGNOSIS, OR TREATMENT
Informational only. Not medical advice.INFORMATIONAL PLATFORM ONLY — NOT MEDICAL ADVICE, DIAGNOSIS, OR TREATMENT
Head-to-head comparison of P21 and PE-22-28 — mechanism, side effects, legal status, and pricing.
P21 (also P021) is a small peptidergic compound — the tetrapeptide core Asp-Gly-Gly-Leu with an N-terminal acetyl and a C-terminal adamantylated glycine amide (Ac-DGGL(A)G-NH2) — derived from an active region (residues ~148–151) of human ciliary neurotrophic factor (CNTF). It was designed and characterized in the Khalid Iqbal laboratory at the New York State Institute for Basic Research in Developmental Disabilities (NYS IBR). It is an experimental, preclinical compound — NOT FDA-approved and NOT tested in humans in published trials. Distinct from the cyclin-dependent kinase inhibitor protein p21/CDKN1A/WAF1 (a completely different gene product; the two share only the name).
PE-22-28 is a 7-amino-acid synthetic analog of spadin, a peptide fragment (residues 22-28) of the 44-aa propeptide (PE) released during post-translational maturation of sortilin (the neurotensin receptor-3). It is studied in preclinical models as a fast-acting antidepressant that works by selectively blocking the TREK-1 two-pore potassium channel. There is no established use for hair growth — that is a separate compound and the two should not be confused.
P21
PE-22-28
Category
Legal Status
Mechanism
Half-life
Side Effects
COA-verified vendors · trust score ≥70 required · single-vial price — bulk/bundle deals may be lower
P21
PE-22-28
COA corpus from Disclosed Labs — independently tested batches only.
P21
2
COAs
99.1%
Avg purity
1
Labs
PE-22-28
13
COAs
99.6%
Avg purity
7
Labs
Evidence is preclinical (rodent) only. Key publication: Kazim, Blanchard, Dai, Tung, LaFerla, Iqbal & Iqbal, Neurobiology of Disease 2014 (PMID 25046994) reported that chronic oral P021 rescued cognition, boosted dentate-gyrus neurogenesis, and reduced tau hyperphosphorylation in 3xTg-AD mice. Additional preclinical papers from the Iqbal group (and collaborators) have shown dendritic/synaptic rescue in AD and aging rodent models (e.g., Kazim et al., Alzheimer's Res Ther 2017). No Phase 1/2/3 human trials have been published; no human safety or pharmacokinetic data exist. Grey-market vendor material is unvalidated — purity, identity, and dosing are not verifiable.
Mazella, Borsotto and colleagues at Nice, France identified spadin (Mazella et al., PLoS Biology 2010, PMID 20405001) and subsequently developed shortened PE 22-28 analogs with ~300× improved TREK-1 affinity and longer in vivo half-life (Djillani et al., Front Pharmacol 2017, PMID 28955242). In mouse antidepressant assays (forced swim, tail suspension, novelty-suppressed feeding), acute or 4-day IP dosing at ~3–4 μg/kg produced effects comparable to chronic SSRI treatment; oral gavage at 1 mg/kg was also active. The G/A-PE 22-28 modification extended duration of action to ~21–23 hours. Chronic dosing did not produce cardiac or seizure signals in rodents. No human clinical trials have been conducted. A detailed review of TREK-1 blockers for depression is available in Djillani et al., Pharmacol Ther 2019 (PMID 30291907).
P21 and PE-22-28 are both in the Cognitive category and may have overlapping mechanisms. Researchers should review both profiles carefully, understand the mechanisms of action, and monitor the relevant biomarkers when combining compounds in the same class. As always, consult a licensed healthcare provider before making any decisions about combining research compounds.
This platform provides informational tools only, not medical advice. This comparison is for educational purposes only. Consult a licensed provider.
Contraindications
Lab Testing
Disclosed Labs