Peptides›Cognitive›P-21

P-21

/ Synthetic 11-residue peptide derived from a region of ciliary neurotrophic factor (CNTF); proposed neurogenic and neuroprotective agent

TIER 3 · PreclinicalN = 0 · TESTING PENDING

ALIAS · P21 · CNTF-mimetic peptide · P21 (Iqbal lab) · P-021

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Research use onlyAny dose figures below describe what specific cited studies used, reported factually. Nothing on this page is guidance for human use.READ FIRST →

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§ A · Identity

Primary sequence— sequence not captured —

MW · —CLASS · Synthetic 11-residue peptide derived from a region of ciliary neurotrophic factor (CNTF); proposed neurogenic and neuroprotective agentCATEGORY · Cognitive

Tier 3 (rodent only) and substantially single-lab. Almost all published P-21 / P-021 work originates from the Khalid Iqbal laboratory at the New York State Institute for Basic Research in Developmental Disabilities. No independent replication of the principal cognitive or neurogenic findings, and no human trials.

§ B · Mechanism of action

P-21 (also written P-021) was designed by the Iqbal group as a small peptide mimetic of a neurogenic region of CNTF, intended to engage the CNTF receptor pathway and downstream JAK-STAT and BDNF signalling without the systemic toxicity that limited recombinant CNTF clinical development. The proposed mechanism is enhanced adult hippocampal neurogenesis, BDNF upregulation, and reduced tau hyperphosphorylation in rodent Alzheimer's disease models.

§ C · Human clinical evidence

Tier 3. Rodent studies in 3xTg-AD, APP/PS1, and aging models report improvements in hippocampal neurogenesis, synaptic markers, and behavioural memory measures. No Phase 1 or later human trials. No independent (non-Iqbal-lab) replication of the principal cognitive and neurogenic findings.

§ D · Primary literature

PubMed22083255Bolognin S et al. — An experimental rat model of sporadic Alzheimer's disease and rescue of cognitive impairment with a neurotrophic peptide · Acta Neuropathologica · rodentIn a streptozotocin-induced rat model of sporadic Alzheimer-like pathology, the CNTF-derived neurotrophic peptide rescued cognitive impairment and reduced tau hyperphosphorylation; the paper introduces the P-021 peptide tested by the Iqbal group.Limitations: Single-lab; rodent only; sporadic-AD model relevance to human disease debated.2012

PubMed25046994Kazim SF et al. — Disease modifying effect of chronic oral treatment with a neurotrophic peptidergic compound in a triple transgenic mouse model of Alzheimer's disease · Neurobiology of Disease · rodentChronic oral P021 in 3xTg-AD mice reduced amyloid and tau pathology, increased hippocampal neurogenesis markers, and improved cognitive performance versus vehicle controls.Limitations: Single-lab; rodent transgenic model; oral bioavailability not characterised in standard PK terms.2014

§ F · Safety signal

No human safety database. Rodent studies report tolerability at the doses used but no formal toxicology package supporting clinical development is published.

§ H · Regulatory status

Regulatory status

FDA status:: Not FDA-approved

§ I · Notable gaps and controversies

Single-lab dominance is the dominant gap. The published preclinical evidence base for P-21 / P-021 is almost entirely from a single research group; vendor-sold material has no independent identity or activity characterisation, and no Western or Asian regulatory authority has reviewed the molecule for clinical use. Translational claims for Alzheimer's disease or general cognitive enhancement in vendor channels rest on rodent data from one program.