Pair page
P21 with Semax
Mechanism-tag overlap and published literature for P21 and Semax, pulled verbatim from each Kalios compound profile. Kalios is a literature reference, not a recommendation.
Mechanism overlap
Mechanism tags are verbatim labels on each compound's profile. Generic tags ("peptide", "small-molecule", "research-chemical") are excluded from this overlap view. Tags are descriptive — not an inference about combined effect.
cntf-derived-neurotrophic-mimetic
acth-analogneuroprotectivenootropic
Co-administration notes from the literature
Verbatim summary text pulled from each compound's profile data. Researchers studying P21 and Semax have published these mechanism-level observations. Not a co-administration recommendation.
Semax drives BDNF elevation via intranasal ACTH(4-7)-derived MC4R-adjacent signaling. P21 drives BDNF via CNTF-pathway mimicry. These are mechanistically distinct inputs into the same downstream neurotrophic target. Popular nootropic combination in community protocols; no clinical safety validation.
Quick facts
P21
Semax
Literature table
Classified references from each compound profile. Click a column header to sort. Click a PMID to open PubMed. Findings are quoted verbatim from each profile's literature_summary; nothing here is added or interpreted.
| Year | Compound | Source | Finding |
|---|---|---|---|
| 2017 | P21 | Kazim SF, Blanchard J, Bianchi R, Iqbal K. Early neurotrophic pharmacotherapy rescues developmental delay and Alzheimer's-like memory deficits in the Ts65Dn mouse model of Down syndrome. Sci Rep. 2017;7:45561. PMID: 28368026. PMID 28368026 | preclinical, in vivo |
| 2017 | P21 | Kazim SF, Iqbal K. Chronic intermittent fasting reverses cognitive impairment in aged mice. Neurobiol Aging. 2017. | preclinical, in vivo |
| 2015 | P21 | Khatoon S, Chalbot S, Bolognin S, Puoliväli J, Iqbal K. Elevated tau level in aged rat cerebrospinal fluid reduced by treatment with a neurotrophic compound. J Alzheimers Dis. 2015;47(3):557-564. PMID: 26401700. PMID 26401700 | preclinical, in vivo |
| 2014 | P21 | Kazim SF, Blanchard J, Dai CL, Tung YC, LaFerla FM, Iqbal IG, Iqbal K. Disease modifying effect of chronic oral treatment with a neurotrophic peptidergic compound in a triple transgenic mouse model of Alzheimer's disease. Neurobiol Dis. 2014;71:110-130. PMID: 25046994. PMID 25046994 | preclinical, in vivo |
| 2014 | P21 | Blanchard J, Wanka L, Tung YC, Cárdenas-Aguayo Mdel C, LaFerla FM, Iqbal K, Grundke-Iqbal I. Pharmacokinetics and efficacy of P021 in a novel mouse model of Alzheimer's disease. Drug Des Devel Ther. 2014;8:711-717. PMID: 25028537. PMID 25028537 | preclinical, in vivo |
| 2012 | P21 | Bolognin S, Blanchard J, Wang X, Basurto-Islas G, Tung YC, Kohlbrenner E, Grundke-Iqbal I, Iqbal K. An experimental rat model of sporadic Alzheimer's disease and rescue of cognitive impairment with a neurotrophic peptide. Acta Neuropathol. 2012;123(1):133-151. PMID: 22454023. PMID 22454023 | preclinical, in vivo |
| 2010 | P21 | Li B, Wanka L, Blanchard J, Liu F, Chohan MO, Iqbal K, Grundke-Iqbal I. Neurotrophic peptides incorporating adamantane improve learning and memory, promote neurogenesis and synaptic plasticity in mice. FEBS Lett. 2010;584(15):3359-3365. PMID: 20638986. (Original P21 design and p… PMID 20638986 | preclinical, in vivo |
| 2021 | P21 | Sarkar B, Kumar D, Sasmal D, Mukhopadhyay K. CNTF-pathway–mimetic small molecules: mechanistic overview. Curr Alzheimer Res. 2021. (Independent review of CNTF-mimetic programs.) | mechanism / discovery |
| 2018 | P21 | Baazaoui N, Iqbal K. A Novel Therapeutic Approach to Treat Alzheimer's Disease by Neurotrophic Support During the Period of Synaptic Compensation. J Alzheimers Dis. 2018;62(3):1211-1218. PMID: 29526843. PMID 29526843 | research article |
| 2017 | P21 | Baazaoui N, Iqbal K. Prevention of amyloid-β and tau pathologies, associated neurodegeneration, and cognitive deficit by early treatment with a neurotrophic compound. J Alzheimers Dis. 2017;58(1):215-230. PMID: 28527206. PMID 28527206 | research article |
| 2016 | P21 | Kazim SF, Iqbal K. Neurotrophic factor small-molecule mimetics mediated neuroregeneration and synaptic repair: emerging therapeutic modality for Alzheimer's disease. Mol Neurodegener. 2016;11(1):50. PMID: 27400670. PMID 27400670 | research article |
| 2016 | P21 | Iqbal K, Liu F, Gong CX. Tau and neurodegenerative disease: the story so far. Nat Rev Neurol. 2016;12(1):15-27. PMID: 26635213. (Parent-context tau review.) PMID 26635213 | research article |
| 2002 | Semax | Skvortsova VI, Platonova IA, Tvorogova TV, Miasoedov NF. Effect of semax on disability and handicap indexes in patients survived carotid ischemic stroke. Zh Nevrol Psikhiatr Im S S Korsakova. 2002;102(Suppl 5):36-39. | human study |
| 2020 | Semax | Filippenkov IB, Stavchansky VV, Denisova AE, et al. Novel Insights into the Protective Properties of ACTH(4-7)PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia-Reperfusion in Rats. Genes (Basel). 2020;11(6):681. | preclinical, in vivo |
| 2013 | Semax | Glazova NY, Sebentsova EA, Manchenko DM, et al. Prolonged beneficial effect of neonatal treatment with Semax on the grooming behavior of elderly rats. Bull Exp Biol Med. 2013;155(6):731-733. | preclinical, in vivo |
| 2011 | Semax | Stavchansky VV, Tvorogova TV, Botsina AY, Skvortsova VI, Limborska SA, Myasoedov NF, Dergunova LV. The effect of Semax and its C-end peptide PGP on expression of neurotrophins and their receptors in rat brain during incomplete global ischemia. Mol Biol (Mosk). 2011;45(6):1026-10… | preclinical, in vivo |
| 2010 | Semax | Shadrina M, Kolomin T, Agapova T, et al. Comparison of the temporary dynamics of NGF and BDNF gene expression in rat hippocampus, frontal cortex, and retina under Semax action. J Mol Neurosci. 2010;41(1):30-35. | preclinical, in vivo |
| 2007 | Semax | Agapova TY, Agniullin YV, Shadrina MI, Shram SI, Slominsky PA, Lymborska SA, Myasoedov NF. Neurotrophin gene expression in rat brain under the action of Semax, an analogue of ACTH(4-10). Neurosci Lett. 2007;417(2):201-205. | preclinical, in vivo |
| 2007 | Semax | Storozheva ZI, Proshin AT, Sherstnev VV, Stolyarov ID, Boĭko AN. Effects of Semax on different forms of learning and memory in adult and aged rats. Bull Exp Biol Med. 2007;143(4):482-485. | preclinical, in vivo |
| 2006 | Semax | Dolotov OV, Karpenko EA, Inozemtseva LS, et al. Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain. J Neurochem. 2006;97 Suppl 1:82-86. PMID: 16635254. PMID 16635254 | preclinical, in vivo |
| 2006 | Semax | Volkova MV, Shadrina MI, Kolomin TA, Dolotov OV, Grivennikov IA, Shaburova EV, Solntseva OS, Myasoedov NF, Limborska SA, Slominsky PA. Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain Res. 2006;1117(1):54-60.… PMID 16996037 | preclinical, in vivo |
| 1991 | Semax | Potaman VN, Antonova LV, Dubynin VA, et al. Entry of the synthetic ACTH(4-10) analogue into the rat brain following intravenous injection. Neurosci Lett. 1991;130(1):11-13. | preclinical, in vivo |
| 2001 | Semax | Kost NV, Sokolov OY, Gabaeva MV, Grivennikov IA, Andreeva LA, Myasoedov NF, Zozulya AA. [Semax and selank inhibit the enkephalin-degrading enzymes from human serum]. Bioorg Khim. 2001;27(3):180-183. PMID: 11443939. PMID 11443939 | research article |
| 1997 | Semax | Gusev EI, Skvortsova VI, Miasoedov NF, Nezavibatko VN, Zhuravleva EIu, Vanichkin AV. [Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study)]. Zh Nevrol Psikhiatr Im S S Korsakova. 1997;97(6):26-34. PMID: 11517472. PMID 11517472 | research article |
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Frequently asked
Have P21 and Semax been studied together?
Researchers have published mechanistic-level co-administration discussion of P21 and Semax. No human co-administration trials are catalogued in the Kalios profiles. The pair page lists each compound's classified literature; full citations sit on each individual profile.
What mechanisms do P21 and Semax share?
P21 and Semax do not share a specific mechanism tag on their Kalios profiles. They appear on the same pair page because at least one profile lists the other in its co-administration data.
What is the FDA status of P21 and Semax?
P21: Research only; no IND. Semax: Not approved. FDA-status text is pulled verbatim from each compound profile. See /fda-pcac-2026.html for the broader FDA Pharmacy Compounding Advisory Committee context.
Where can I find the full research on P21 and Semax?
Full citation lists, dosing tables from the literature, reconstitution data, and the FDA / WADA status are on the individual compound profiles: the P21 profile and the Semax profile. The Kalios Stack Research Tool hub lists every compound covered.
Last updated: April 2026