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Home/Compounds/P21
Cognitive

P21

Also known as: P021 · CNTF-derived peptide

CNTF-derived peptide that promotes neurogenesis without CNTF side effects.

C
Grade C
Animal studies only
Human studies28
PubMed citations30
Typical dose500 mcg – 2 mg
Routeintranasal, subcutaneous
Regulatory (US)Compounding legal
Last verified2 days ago
TL;DR · 30-second summary
  • Promotes adult neurogenesis
  • Reduces tau and amyloid pathology in animals
  • No CNTF-related weight loss
  • Intranasal bioavailability demonstrated

Mechanism of action

Small peptide derived from ciliary neurotrophic factor (CNTF). Promotes neurogenesis and inhibits tau/amyloid pathology without systemic CNTF effects like weight loss.

Evidence summary

28
Human studies
30
PubMed citations
9
Clinical trials
C
Evidence grade

Preclinical studies show neurogenesis promotion and cognitive benefits in Alzheimer's models. Intranasal delivery being developed.

Dosing protocols

Educational information only. Consult a licensed provider before using any peptide.
Dose range
500 mcg – 2 mg

Intranasal: 500mcg-2mg daily. Injectable protocols also used. Research stage.

Administration routes
intranasalsubcutaneous

Side effects & safety

Reported side effects
Unknown - limited dataGenerally well tolerated in animal studies
Contraindications
  • Unknown - no human data

Interactions

No documented drug interactions on file.

Regulatory status

United States
Not FDA approved

Not FDA approved. Research peptide.

Compounding
Permitted

Available through compounding pharmacies with valid prescription.

Regulatory data last verified 4/17/2026

Clinical trials

NCT03155620NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) Screening ProtocolActive Not Recruiting · Phase 2 · Advanced Malignant Solid Neoplasm · n=1377NCT04914845A Phase 1 Open-label Study of KPT-9274 in Patients With Relapsed and Refractory Acute Myeloid LeukemiaCompleted · Phase 1 · Acute Myeloid Leukemia · n=16NCT04284774NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice)- Phase 2 Subprotocol of Tipifarnib in Patients With Tumors Harboring HRAS Genomic AlterationsActive Not Recruiting · Phase 2 · Malignant Solid Neoplasm · n=5NCT04113122Senescence and the Early Ageing Phenotype After Chemotherapy for Testicular Cancer: the SEA-CAT StudyRecruiting · N/A · Testicular Cancer · n=192NCT04259879Evaluation of p21 Induction and Molecular Pathways Related to Short-term Fasting ResponseCompleted · N/A · Fasting · n=20NCT02064244Does the Inferior Vena Cava Size Assessment Help in the Management of Acute Kidney Injury in Critically Ill Patients?Completed · Acute Renal Failure · n=33NCT01664000A Phase 1, Open-Label, Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of Kevetrin (Thioureidobutyronitrile) Administered Intravenously, in Patients With Advanced Solid TumorsCompleted · Phase 1 · Solid Tumors · n=48NCT00423865A Phase I Study of Weekly Low-Dose Cisplatin Plus Escalating Doses of Oral RAD001(Everolimus) for Patients With Advanced Solid TumorsCompleted · Phase 1 · Unspecified Adult Solid Tumor, Protocol Specific · n=30NCT01549054A Single-center, Randomized, Open-label, Two-part Study to Evaluate Bioavailability of Prototype Third-generation Formulations of E5501 Relative to Second-generation Tablet Formulation in Healthy SubjectsCompleted · Phase 1 · Idiopathic Thrombocytopenic Purpura · n=28

Citations

PMID 37442187Chen Y, Zeng H et al. · Azurin Regulates P21 and Enhances the Sensitivity of Osteosarcoma Cells to Cisplatin.Alternative therapies in health and medicine (2026)HumanPMID 40382842Abuelafia AM, Santofimia-Castaño P et al. · KRAS inhibition reverses chemotherapy resistance promoted by therapy-induced senescence-like in pancreatic ductal adenocarcinoma.Translational oncology (2026)HumanPMID 41571637Luo L, Wang Y et al. · CDK2 inhibitor BLU-222 synergizes with CDK4/6 inhibitors in drug resistant breast cancers through p21/p27 induction.Nature communications (2026)HumanPMID 40585759Yang J, Wu S et al. · Engineered Exosome-Based Senolytic Therapy Alleviates Stroke by Targeting p21+CD86+ Microglia.Exploration (Beijing, China) (2025)HumanPMID 39002691Chang S, Ren D et al. · Therapeutic SHPRH-146aa encoded by circ-SHPRH dynamically upregulates P21 to inhibit CDKs in neuroblastoma.Cancer letters (2024)HumanPMID 39592934Mottolese N, Loi M et al. · Effects of a ciliary neurotrophic factor (CNTF) small-molecule peptide mimetic in an in vitro and in vivo model of CDKL5 deficiency disorder.Journal of neurodevelopmental disorders (2024)HumanPMID 38255799Ooi LC, Ho V et al. · p21 as a Predictor and Prognostic Indicator of Clinical Outcome in Rectal Cancer Patients.International journal of molecular sciences (2024)HumanPMID 38810561Xu S, Ma B et al. · Development of a PAK4-targeting PROTAC for renal carcinoma therapy: concurrent inhibition of cancer cell proliferation and enhancement of immune cell response.EBioMedicine (2024)HumanPMID 37042028Lozupone M, Dibello V et al. · The development of peptide- and oligonucleotide-based drugs to prevent the formation of abnormal tau in tauopathies.Expert opinion on drug discovery (2023)HumanPMID 36831007Pincus MR, Lin B et al. · Peptides That Block RAS-p21 Protein-Induced Cell Transformation.Biomedicines (2023)HumanPMID 36951731Zuo C, Baer JM et al. · Stromal and therapy-induced macrophage proliferation promotes PDAC progression and susceptibility to innate immunotherapy.The Journal of experimental medicine (2023)HumanPMID 38139316Manousakis E, Miralles CM et al. · CDKN1A/p21 in Breast Cancer: Part of the Problem, or Part of the Solution?International journal of molecular sciences (2023)HumanPMID 36291618Baazaoui N, Iqbal K · Alzheimer's Disease: Challenges and a Therapeutic Opportunity to Treat It with a Neurotrophic Compound.Biomolecules (2022)HumanPMID 35587060Helal NS, Moussa MM et al. · Differential expression of metallothionein and p21 in gastric cancer and some precursor lesions.European review for medical and pharmacological sciences (2022)HumanPMID 34813734Wang L, Wang B et al. · Targeting p21Cip1 highly expressing cells in adipose tissue alleviates insulin resistance in obesity.Cell metabolism (2022)HumanPMID 34704055Horsfall AJ, Vandborg BA et al. · A cell permeable bimane-constrained PCNA-interacting peptide.RSC chemical biology (2021)HumanPMID 33547489Kuang Y, Kang J et al. · Multiple functions of p21 in cancer radiotherapy.Journal of cancer research and clinical oncology (2021)HumanPMID 34057082Wei W, Liu Y et al. · Neurotrophic Treatment Initiated During Early Postnatal Development Prevents the Alzheimer-Like Behavior and Synaptic Dysfunction.Journal of Alzheimer's disease : JAD (2021)HumanPMID 32854771Wei W, Wang Y et al. · Prenatal to early postnatal neurotrophic treatment prevents Alzheimer-like behavior and pathology in mice.Alzheimer's research & therapy (2021)HumanPMID 33984593Yang X, Feng Y et al. · Fuzheng Jiedu Xiaoji formulation inhibits hepatocellular carcinoma progression in patients by targeting the AKT/CyclinD1/p21/p27 pathway.Phytomedicine : international journal of phytotherapy and phytopharmacology (2021)Human

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