P21

Areas of active research — not promised effects

Each tag links to other compounds with research into that goal. Research use only: these are areas of study, not human-use claims.

Related by research scope · open each to compare

P021 has no FDA-approved indication and no known Investigational New Drug (IND) application on record. It is not included in the FDA Section 503A Category 2 list (and therefore was not among the 12 peptides removed from that list in April 2026). P021 may be sold for documented in vitro and animal laboratory research only. Prescribing, compounding, dispensing, or administering to humans outside an authorized clinical trial is not legal.

Transparent blend · bci-1.0 · never paid-placement

Primary name

P21

Origin

Derived by epitope mapping of the active region of human ciliary neurotrophic factor (CNTF). A C-terminal adamantylated glycine was appended to improve enzymatic stability and blood-brain barrier permeability, yielding a 578 Da tetra-residue compound (Ac-Asp-Gly-Gly-Leu-Ala-Gly-NH2) developed by Khalid Iqbal and colleagues at the New York State Institute for Basic Research in Developmental Disabilities.

Registry IDs

PubChem CID

56599151

CAS

1246751-68-7

InChIKey

LUJZBZPLIRWWGJ-ZKHAZHQOSA-N

Molecular formula

C27H42N6O8

Molar mass

578.7 g/mol

Monoisotopic

578.30641232 Da

InChIKey

LUJZBZPLIRWWGJ-ZKHAZHQOSA-N

Appearance

White to off-white lyophilized powder

Solubility

Soluble in water and aqueous buffers; DMSO for in vitro stock solutions. The ada…

Sequence not available in current seed.

Stability: The adamantylated C-terminus confers resistance to exopeptidase degradation. Approximately 90% stable in simulated gastric fluid and >97% stable in simulated in

Vial sizes

5 mg · 10 mg

Purity grades

≥98% HPLC

Salt forms

Free base (primary)

• GHS hazard class on file
• PPE & spill response
• Disposal guidance
• Not-for-human-consumption posture

How much research exists, and of what maturity — never a verdict on whether it works.

Mechanism of action

• P021 operates through two complementary neurotrophic axes
• First, it antagonizes leukemia inhibitory factor (LIF) signaling, which normally suppresses adult neurogenesis in the hippocampal dentate gyrus; by attenuating this brake, P021 promotes proliferation and maturation of newborn neurons
• Second, P021 upregulates BDNF transcription; elevated BDNF activates TrkB, engaging the PI3K/Akt cascade and driving inhibitory phosphorylation of GSK3β — a major tau kinase — thereby reducing abnormal tau hyperphosphorylation at multiple epitopes
• Downstream effects include enhanced CREB phosphorylation, increased synaptic density markers (PSD-95, NR2A/2B, synapsin-1), and attenuated amyloid-beta pathology in transgenic rodent models

Pharmacokinetics (ADME)

Half-life

>3 hours (rodent plasma)

PK–PD note: Orally bioavailable; approximately 90% stability in simulated gastric fluid and >97% in simulated intestinal fluid at 37°C. BBB-permeable. No formal multi-compartment PK characterization published in …

Reading the evidence

• Evidence quality and gaps vary by application — see the cited grades above.
• Indexed-article counts span all evidence tiers, not only completed human trials.
• No first-party human-dosing, efficacy, or benefit claims are made here.

Key reviews & evidence-gap sources

• ADDF Cognitive Vitality Report — P021 (last updated May 12, 2025) — Alzheimer's Drug Discovery Foundation neuroscientist-authored report; states no studies have tested P021 in humans and no clinical trials are registered on ClinicalTrials.gov; safety in humans not assessed.
• Iqbal K et al. — Alzheimer's Disease: Challenges and a Therapeutic Opportunity to Treat It with a Neurotrophic Compound (Biomolecules, 2022) — Anchoring mechanistic review from the laboratory that developed P021; describes CNTF-derived adamantylated tetrapeptide, BDNF signaling activation, neurogenesis and disease-modification rationale.
• Neurotrophic factor small-molecule mimetics mediated neuroregeneration and synaptic repair: emerging therapeutic modality for Alzheimer's disease (PubMed 27400746) — Review covering P021 mechanism of disease-modifying effect in AD.
• Prevention of dendritic and synaptic deficits and cognitive impairment with a neurotrophic compound (PMC5488423) — Primary preclinical study in 3xTg-AD mice; describes adamantylation for BBB permeability and P021 preventive effect.

5 registered trials — 1 currently recruiting.

Phase 1
NCT01664000
A Safety, Pharmacokinetic and Pharmacodynamic Study of Kevetrin in Patients With Advanced Solid Tumors

COMPLETED

Phase 2
NCT04284774
Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial

ACTIVE_NOT_RECRUITING

Phase 1
NCT00423865
Cisplatin and Everolimus in Treating Patients With Advanced Solid Tumors

COMPLETED

NA
NCT04113122
Senescence and the Early Ageing Phenotype After Chemotherapy for Testicular Cancer: the SEA-CAT Study

RECRUITING

NA
NCT04259879
Molecular Pathways Related to Short-term Fasting Response

COMPLETED

Summary (literature)

No human safety or toxicology data exist. In rodent studies spanning up to 21 months of chronic dietary exposure, P021 was reported to produce no adverse effects, weight loss, tumors, or signs of pain (cited: PMID 28655344, PMID 34057082). Preliminary binding studies found no sig…

WADA status

Not specifically listed on the WADA 2026 Prohibited List by name. As an experimental, non-approved compound, P021 would likely fall under the S0 (Non-Approved S…

Dominant research route: Oral (diet/feed) in transgenic Alzheimer's mouse models

Chronic oral administration via diet/feed in 3xTg-AD mice and aged rats (Alzheimer's disease models)

Bioavailability: P021 is described as a small water-soluble, orally bioavailable, blood-brain barrier permeable peptide; >90% stable in artificial gastric juice after 30 min and ~100% stable in artificial intestinal fluid after 2 h at 37°C.

Oral/diet route is the most extensively studied in primary literature: Kazim et al. 2014 (PMID 25046994) reported disease-modifying effect of chronic oral treatment in 3xTg-AD mice; Baazaoui & Iqbal 2017 (PMID 28655344) administered P021 in diet from 3 to 21 months in 3xTg-AD mice. No human oral pharmacokinetic data exist.

Subcutaneous implants/injection in mouse models (e.g., 3xTg-AD, C57Bl/6); cited as a standard animal-model route

Bioavailability: No standalone SC pharmacokinetic profile located; plasma half-life reported >3 h in mice (route not specified).

Alzheimer's Drug Discovery Foundation Cognitive Vitality Report notes P021 treatment via subcutaneous implants in 3xTg-AD mice; peptide-db.com states animal-model protocols use subcutaneous or intraperitoneal injection. No human SC data.

Intraperitoneal injection in rodent models (parent peptide 6 and P021 studies in 3xTg-AD and C57Bl/6 mice)

Bioavailability: No IP-specific bioavailability values located.

IP route is referenced for P021 and its parent peptide 6 in rodent neurogenesis/cognition studies; exploring-peptides.com cites 0.1–1 mg/kg IP or SC in rodent models. No human IP data.

No primary peer-reviewed animal or human intranasal study located; appears only in community/aggregator dosing guides

Bioavailability: No intranasal bioavailability data located in retrieved primary sources.

Intranasal route is mentioned in community peptide databases and aggregator monographs (e.g., International Peptide Society, Peptide Initiative) but no supporting primary pharmacokinetic or efficacy study was retrieved. Treated as community route, not cited PK.

Animal & human figures are kept visibly separate so studied animal doses are never misread as human guidance.

Sorted A–Z by vendor — never by price

Weekly median $/mg from the live vendor crawl.

Researched storefront prices, bucketed

What each test proves — general guidance, plus this compound's researched purity data

Purity on the current market (researched)

Vendor-stated ≥99% HPLC purity (e.g., True Lab Peptides '≥99% purity', Peptides Lab UK '>99% HPLC-verified purity', Verified Peptides '99%+ Pure'). These are vendor-supplied claims, not independently verified third-party lab results retrieved for this compound.

Independent labs cited for this compound

No FDA recall, seizure, warning letter, or criminal enforcement action specifically naming P21/P021 was found in FDA warning-letter or import-alert records retrieved. P21 is not an FDA-approved drug; any marketed product with therapeutic claims would be subject to enforcement as an unapproved new drug under Import Alert 66-41, but no compound-specific recall was located.

Buyer red-flag checklist

• P21/P021 is not FDA-approved for any medical, therapeutic, or diagnostic use (confirmed via FDA UNII registry disclaimer and vendor disclosures).
• No compound-specific FDA warning letter, recall, or criminal enforcement action was found — enforcement, if any, would proceed under the generic unapproved-new-drug framework (Import Alert 66-41).
• No independent third-party lab test (Janoshik/MZ Biolabs/Finnrick) publicly quantifying P21 purity or underdosing was retrieved; only vendor-supplied COA claims of ≥99% HPLC purity are available.
• Some P21 vendors sell nasal-spray formulations without publishing a COA or HPLC report, per community reports.
• P21 is listed on informal community 'WADA banned peptides' lists; no authoritative WADA Prohibited List entry naming P21/P021 was retrieved from a primary WADA/USADA source in this search.
• Vendor-supplied COAs are widely acknowledged in the peptide community as susceptible to forgery; independent re-testing (e.g., Janoshik) is recommended before trusting purity claims.

GMP vs research-grade: the chemistry (SPPS + HPLC + MS) is identical — the difference is the quality system.

Underdosing / mislabeling: No independent third-party lab test results (Janoshik, MZ Biolabs, Finnrick aggregates) specifically quantifying P21/P021 purity or underdosing prevalence were retrieved. Community discussions note some P21 vendors sell without providing a COA or HPLC report, but no de-identified aggregate underdosing rate could be sourced.

• Detention Without Physical Examination of Unapproved New Drugs Promoted In The U.S. Applies to unapproved new drug products (including peptides marketed with disease-treatment or structure/function claims) from firms on the Red List. P21 has no FDA-approved drug application.66-41
• An RUO label is not an import exemption — CBP judges actual intended use.
• Lyophilized powder is ambient-stable in transit; temperature control needed for > 7-day transit.
• US-warehouse vendors dodge import scrutiny — they cost more but ship more reliably.

Every item dated & sourced

Not specifically named on the WADA Prohibited List. As a pharmacological substance not approved by any governmental health authority for human therapeutic use, P21/P021 would fall under S0 (Non-Approved Substances) of the WADA Prohibited List by category definition. This is an inferred classification based on S0 scope, not an explicit WADA listing.

No granted patents identified in current seed. Composition-of-matter coverage is limited given the peptide's synthetic origin.

• IACUC / IRB research context
• RUO buyer responsibilities & documentation
• Veterinary / alternative-use where lawful
• Jurisdiction-aware "who may lawfully obtain"

What people discuss

Reported concerns — discussion, not established effects

Reading caveats

• Small-n self-experimentation anecdotes
• Enthusiast / nootropic-community framing
• Vendor-affiliated content present in results
• No completed human RCT; mechanism extrapolated from mouse studies
• Self-selection toward positive responders in public reports

Manually researched from reddit, youtube— theme weights are research estimates, not live counts; aggregated & de-identified. No individual posts, quotes, or usernames are ever shown.

Relative research / market volume — populated once the activity stream is wired

Inline tooltips for lyophilized, RUO, EU/mg, SPPS, 503A and more.

Toggle plain-language ↔ scientific in the header.

• How to read a COA
• Free base vs acetate
• Understanding evidence grades

Synthetic CNTF-derived tetrapeptide (Ac-DGGLAG-NH2) investigated preclinically for neurogenesis, tau reduction, and cognition in Alzheimer's disease models. Approximately 18 articles are indexed (literature last scanned 2026-05-29). US regulatory status: Research Use Only — not FDA-approved, no IND, not compoundable. Research use only.

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