Cyclic Glycine-Proline

Dosing from the Literature

Published for brain disease: rodent doses of cGP alone, and a registered Alzheimer’s trial of NA-831, the same molecule, that lists 10, 20 or 40 mg a day by mouth (NCT03538522). Not published: a peer-reviewed report of that trial, or a human dose of cGP alone in any peer-reviewed paper.

The table records each dose as its source gives it, from registry records and a sponsor’s abstract to the supplement maker’s description and the main rodent experiments; each row names its source. They are research doses and a seller’s description, not recommendations.

What It Is

Cyclic glycine-proline, or cGP, is two amino acids, glycine and proline, joined into a ring: a cyclic dipeptide (Hu et al., 2024), of the kind chemists call a diketopiperazine (Guan et al., 2007). Its formula is C7H10N2O2 and its weight 154.17 g/mol; other names include cyclo(Gly-Pro), cyclo(Pro-Gly) and cycloprolylglycine (PubChem). It is not a peptide chain like most compounds on this site. It forms in the body from IGF-1: enzymes cut off the hormone’s first three amino acids, glycine-proline-glutamate (GPE), and one form of GPE closes into cGP after the glutamate is removed (Guan et al., 2023). It has been measured in rat brain (Gudasheva et al., 1996), in human blood and spinal fluid (Fan et al., 2018) and in human milk (Galante et al., 2020), and found in foods such as coffee, beef and blackcurrants (Hu et al., 2024).

Two groups built most of its record, under two names. In Moscow, T. A. Gudasheva and colleagues at the Institute of Pharmacology of the Russian Academy of Medical Sciences identified “cyclo-prolylglycine” in rat brain in 1996, at 2.8 nmol per gram, and called it a memory-facilitating substance (Gudasheva et al., 1996); a year later they reported that the memory drug GVS-111 turns into it in rat brain (Gudasheva et al., 1997). GVS-111 is noopept, which the Zakusov Research Institute of Pharmacology in Moscow developed and brought into medical use (Boyko et al., 2018). In Auckland, Jian Guan and colleagues studied it as a product of IGF-1, reported brain protection in rats (Guan et al., 2007) and proposed in 2014 that it regulates how much IGF-1 is free to act (Guan et al., 2014). The Auckland group also measured it in people, in blood, spinal fluid and brain tissue (Fan et al., 2019; Fan et al., 2018; Kang et al., 2021).

As a drug, the molecule reached human trials under the code NA-831, or traneurocin: FDA’s substance registry lists both among the names of cyclo(prolylglycyl), including “NA 831 [WHO-DD]”, the form the WHO Drug Dictionary uses (FDA’s substance registry, UNII W7O69J5F2B), and PubChem lists the same names (PubChem). The match rests on those records: the sponsor’s abstracts give no structure, calling NA-831 “a small drug molecule” (Tran et al., 2024, abstract e095627), and a 2022 review lists its formula and weight as “not disclosed” while describing it as “an endogenous compound, present in the human brain” (ADDF, 2022). Its sponsor, Biomed Industries of San Jose, California (Tran et al., 2024, abstract e095627), registered a Phase 2 in Alzheimer’s disease that ran in 2018 and 2019, and three COVID-19 trials (NCT03538522; NCT04452565; NCT04540185; NCT04480333). Two relatives of cGP are drugs in their own right: NNZ-2591, a lab-made analog modified for better bioavailability (Guan et al., 2007), which Neuren Pharmaceuticals tested in an open-label Phase 2 in 18 children aged 3–12 with Phelan-McDermid syndrome (Neumeyer et al., 2026), and trofinetide, an analog of GPE (Neul et al., 2022), approved by FDA in March 2023 as Acadia Pharmaceuticals’ Daybue for Rett syndrome (Daybue label). Neither is cGP. As a supplement, capsules of New Zealand blackcurrant fruit powder and collagen peptides standardized to cGP are sold by a company that names Guan as its chief science officer (maker’s listings, read October 4, 2026); the group’s 2023 review declares Guan an employee of it (Guan et al., 2023).

PubMed returns 95 records for its dipeptide names (October 4, 2026). About half test or measure cGP in cells, animals or people; the rest are reviews, chemistry papers, reports of it among compounds found in microbes and marine organisms, papers on drugs that turn into it, and papers on larger cyclic peptides that match the search. No PubMed record names NA-831 or traneurocin in its title or abstract; a plain search for traneurocin returns 30 records because PubMed maps the name to cyclo(prolylglycyl), the molecule’s chemical name (PubMed, searched October 5, 2026). No paper reports a trial that gave cGP alone to people (PubMed, searched October 4, 2026).

Mechanism of Action

The findings below come from test tubes, cell cultures and rodents, plus one small human study of spinal-fluid levels (Fan et al., 2018); none of the proposed mechanisms has been confirmed in people. The two groups describe different mechanisms, and the Auckland group calls the receptor findings for GPE and cGP “inconclusive” (Guan et al., 2023).

• IGF-1 and its binding protein IGFBP-3 (the Auckland proposal) — Most IGF-1 in the blood is held by binding proteins, mainly IGFBP-3, and only free IGF-1 can act on its receptors (Guan et al., 2023). cGP comes from the end of IGF-1 that binds IGFBP-3. In a test-tube assay, cGP raised the amount of free IGF-1 when cGP was in excess and lowered it when IGF-1 was in excess, and in human blood-vessel cells it raised IGF-1’s effect when IGF-1 was low and lowered it when IGF-1 was high; the authors wrote that how cGP acts on this binding “is entirely unknown” (Guan et al., 2014). The group’s 2023 review still lists the mechanisms beyond this competition among the gaps in its research (Guan et al., 2023).
• AMPA receptors and BDNF (the Moscow proposal) — At 1 µM, cGP strengthened AMPA-receptor currents in rat cerebellar Purkinje cells (Gudasheva, Grigoriev et al., 2016), and at 0.1 µM and 1 mM it raised BDNF, a nerve growth factor, in cultured neuronal cells (Gudasheva, Koliasnikova et al., 2016). Blockers of AMPA receptors and of Trk receptors, which BDNF acts on, prevented its anxiety-reducing effect in BALB/c mice (Gudasheva et al., 2020) and its protective effect in cells (Gudasheva et al., 2022). Two weeks of injections raised Bdnf gene activity in the frontal cortex of mice (Abdullina et al., 2022).
• GABA-A receptors — In rat Purkinje cells, 1 µM cGP slowly raised GABA-activated currents to 177% of control; the authors suggest a second-messenger process (Sharonova et al., 2019).
• Akt and the MDM2–p53 pathway — In human fetal neural stem cells exposed to hydrogen peroxide, cGP reduced cell death in a dose-dependent way through Akt signalling and the protein MDM2, and an MDM2 blocker reduced the protection (Murotomi et al., 2023).
• Opioid receptors (in mice) — Naloxone, an opioid blocker, reduced cGP’s pain-relieving effect in a hot-plate test (Ferro et al., 2015) and restored the saliva flow that cGP reduced (Melo et al., 2020).
• Absorption and reaching the brain — Given by mouth to nursing rats, cGP appeared in their milk and reached their pups (Singh-Mallah et al., 2016). In men with Parkinson’s, the level in spinal fluid was 52% of the blood level before blackcurrant capsules and 71% after (Fan et al., 2018). The Auckland group proposes that its ring shape resists breakdown by enzymes and helps it enter tissue (Guan et al., 2023).

What the Research Shows

The results below are in rodents; the human work is in the next section.

• Brain injury and stroke (rats) — Given into the brain’s fluid spaces 2 hours after a hypoxic-ischemic injury, cGP reduced damage in the cortex, hippocampus and striatum (Guan et al., 2007); a single 0.2 µg dose, in 12 rats against 12 on saline, restored the hippocampus’s capillaries (Guan et al., 2014). In rats with incomplete global brain ischemia, 1 mg/kg into the belly after the injury restored limb-placing and movement scores (Povarnina et al., 2016). In rats fed pellets containing cGP before a small stroke of the forepaw area of the cortex, the lower of two doses cut the days needed to learn a changed task (Kaneko et al., 2022).
• Memory and Alzheimer’s models — In rats, 0.1 mg/kg into the belly was anti-amnesic in a passive-avoidance test (Gudasheva et al., 1996). In 9–11-month-old APP/PS1 mice, 20 mg/kg into the nose over 28 days improved water-maze memory and cut hippocampal plaques from 42.3 to 14.5 per mm² (Arora & Sharma, 2023). In rats infused with amyloid-beta, cGP given alongside reduced cell death and pro-inflammatory interleukins (Aguado-Llera et al., 2019).
• Developing brains (rats) — Rat mothers given 3 mg/kg by mouth daily while nursing passed cGP into their milk; their pups showed better recognition memory (Singh-Mallah et al., 2016) and, as adults, moderately better spatial memory, with more capillaries and astrocyte branches in the hippocampus (Singh-Mallah et al., 2022).
• Anxiety and depression models (Moscow) — In rats, 0.05 mg/kg into the belly lengthened time in the open arms of a maze 9-fold (Gudasheva et al., 2001); in fearful BALB/c mice, 0.01–0.10 mg/kg raised activity 1.8–2.1-fold, with no effect in C57Bl/6 mice (Seredenin et al., 2002). In a mouse strain with depression-like behaviour, 1 or 2 mg/kg a day for two weeks reduced immobility in a tail-suspension test (Abdullina et al., 2022).
• Blood pressure and fat (obese rats) — In rats made obese on a high-fat diet, cGP given from 11 to 15 weeks of age lowered systolic blood pressure and retroperitoneal fat, but not body composition or insulin (Li et al., 2020), and normalized the synapse protein synaptophysin in the hippocampus (Li et al., 2019).
• Pain and inflammation (mice) — Injected into the belly, cGP reduced pain behaviour in several tests and paw swelling, without changing movement (Ferro et al., 2015).
• The other direction: growth — In mice given an IGF-1-secreting lymphoma, 25 mg/kg a day under the skin by pump delayed tumours: all 6 mice on saline had tumours by day 10, half of the 6 treated mice by day 16; started later, it left tumours 20% smaller (Guan et al., 2014). In nursing rats it sped the shrinking of the mammary glands after weaning (Singh-Mallah et al., 2017).

Human Data

No peer-reviewed paper reports a trial that gave cGP alone to people (PubMed and Europe PMC, searched October 4, 2026). Published in journals: studies that measured the body’s own cGP, two open-label studies of food-derived capsules that contain it (Fan et al., 2018; Chen et al., 2025), and conference abstracts from the sponsor of NA-831, the same molecule as a drug, printed in supplements of Alzheimer’s & Dementia (Tran et al., 2024, abstract e095627). Registered: four trials of NA-831, none with results posted; the abstracts report results from one, an Alzheimer’s Phase 2, and a 2025 abstract names its registration (ClinicalTrials.gov, searched October 4, 2026; Tran, 2025). Two more active registrations list blood cGP among their measures without being trials of cGP: an industry-sponsored, randomized, open-label comparison of two doses of a bovine collagen-peptide supplement, which the record does not say contains cGP, in 72 stressed but otherwise healthy adults aged 35–70 (NCT07572240, active, not recruiting; primary completion estimated November 2026), and a University of Connecticut randomized, placebo-controlled Phase 1 trial of blackcurrant extract capsules (784 mg or 1,176 mg a day) for bone loss in 159 planned postmenopausal women aged 45–70, with plasma cGP and IGF-1 among its other measures (NCT07365514, recruiting; primary completion estimated February 2028).

• NA-831 Phase 2 in Alzheimer’s disease (NCT03538522) — A randomized, placebo-controlled trial by Biomed Industries, registered with 10, 20 or 40 mg by mouth once a day for 24 weeks in adults aged 55–85 with mild cognitive impairment due to Alzheimer’s, and the Clinical Dementia Rating Sum of Boxes (CDR-SB) as its main measure. It lists 126 enrolled and completion in 2019; no results are posted, and no peer-reviewed paper has been published (PubMed, searched October 4, 2026). The sponsor’s 2024 conference abstract describes 112 participants, half on placebo, given 10 mg a day for mild cognitive impairment or 30 mg for mild to moderate Alzheimer’s, and reports an ADAS-Cog-13 score 4.1 points better than placebo after 24 weeks in mild to moderate Alzheimer’s (p = 0.001), improvement in 78% on the CIBIC-Plus scale and no serious adverse events (Tran et al., 2024, abstract e095627); a 2025 abstract gives the same figures and names this registration (Tran, 2025). Another 2024 abstract adds that 12 of the 18 participants with diabetes among the 56 on NA-831 reported a loss of 17–23% of their body weight over 6 months (Tran et al., 2024, abstract e095715). The Alzheimer’s Drug Discovery Foundation’s 2022 review of earlier abstracts gives 32 people with mild cognitive impairment and 24 with Alzheimer’s, reports from those abstracts an ADAS-Cog13 score 3.4 points better than placebo on 10 mg a day for 24 weeks (p = 0.01), and notes that the results “have not been published in a peer-reviewed journal” (ADDF, 2022). The registration admits only adults scoring 23 or more on the Mini-Mental State Exam (MMSE) and lists no 30 mg dose; the 2024 and 2025 abstracts’ headline result comes from people with mild to moderate Alzheimer’s (MMSE 17–21) on 30 mg, and none of the sponsor’s abstracts read for this page, nor ADDF’s review of earlier ones, gives a result on the registered main measure, the CDR-SB (NCT03538522; Tran et al., 2024, abstract e095627; Tran, 2025; ADDF, 2022).
• NA-831 in depression (abstract only) — The sponsor’s 2024 Phase 2 abstract also reports a randomized study of 20 or 40 mg a day against placebo for 6 weeks in 32 adults with major depressive disorder, with a difference of about 7 points on the MADRS scale (Tran et al., 2024, abstract e095627). No registration of it turned up on ClinicalTrials.gov (searched October 4, 2026).
• NA-831 Phase 1 (abstracts, as reviewed by ADDF) — In healthy volunteers given doses that rose every two days, from 5 to 20 mg a day in two cohorts and from 30 to 50 mg in two others, NA-831 peaked in the blood 2–3 hours after a dose, with a mean serum half-life of about 7 hours and no adverse effects reported; a 2021 abstract reported it well tolerated up to 100 mg a day (ADDF, 2022). No full report has been published.
• NA-831 in COVID-19, and Phase 3 plans (no results) — Three COVID-19 registrations, a Phase 2/3 of 30 mg capsules alone or with atazanavir or dexamethasone for 5 days in 525 planned patients (NCT04452565), a Phase 3 with the oral polio vaccine in 3,600 planned (NCT04540185) and a Phase 1 of an inhaled form with remdesivir in 45 planned volunteers (NCT04480333), show status unknown and no results. A 2025 abstract describes a 600-person Phase 3 in early Alzheimer’s comparing NA-831 30 mg a day, donanemab, and the two together, each against placebo, and says it is “underway across more than 30 sites” (Tran et al., 2025); a 2024 abstract had described the same design with lecanemab in place of donanemab (Tran et al., 2024, abstract e095755). No registration of either turned up on ClinicalTrials.gov (searched October 4, 2026).
• Blackcurrant capsules in Parkinson’s disease (Fan et al., 2018) — An open-label study with no placebo: 11 men with Parkinson’s took 300 mg of blackcurrant anthocyanin concentrate (35% anthocyanins) twice a day for 28 days. The capsules contained cGP, in an amount the paper does not give. Seven of the 11 men gave paired spinal-fluid samples for cGP. Leaving out one man whose spinal-fluid cGP rose 16.9-fold (and blood cGP 19-fold) as an outlier, the mean in the other 6 rose from 7.27 to 12.12 ng/mL (p < 0.01); one of the 6 had no change. In the group analysis, blood levels of cGP and IGF-1 did not change (Fan et al., 2018). The men scored better on the emotional well-being part of a quality-of-life questionnaire (p = 0.008), which the researcher who ran the trial says could reflect the attention they received or a placebo effect (Alamri, 2018). The capsules came from a New Zealand supplement company that co-funded the study (Fan et al., 2018).
• “Natural cGP” capsules in type 2 diabetes (Chen et al., 2025) — An open-label, non-randomized study in Wuhan, China, in 38 adults aged 45–80 with type 2 diabetes and nerve damage in the feet, allocated in sequence to 20–25 µg or 40–45 µg of “natural cGP” a day for 6 months, in capsules made from New Zealand food ingredients (ISRCTN84351085). The authors report better protective foot sensation, less macroalbuminuria and normalized blood pressure and HbA1c, and call the findings preliminary, “pending confirmation in larger, controlled studies” (Chen et al., 2025). A New Zealand cGP supplement company co-funded the study and is registered as one of its two sponsors, with Wuhan University of Science and Technology; Guan, whom the company names as its chief science officer, is the registered principal investigator and an author (ISRCTN84351085; Chen et al., 2025; maker’s FAQ, read October 4, 2026). This page read the abstract and the registry record; the full paper was not accessible.
• The body’s own cGP after stroke (Fan et al., 2019) — In 34 patients sampled within 3 days of a stroke and 50 people without stroke, blood cGP was lower in the patients (P = 0.04) and rose over 90 days as they recovered; after adjustment for age and stroke severity, a higher cGP-to-IGF-1 ratio at admission went with fewer neurological deficits at 90 days, in 28 patients. The authors call the study hypothesis-generating and limited by its size (Fan et al., 2019).
• Parkinson’s, ageing and Alzheimer’s (observational) — In 178 people with Parkinson’s and 23 healthy older controls, the cGP-to-IGF-1 ratio went with better cognitive scores in the controls but not in the patients (Fan et al., 2020). In brain tissue from 15 people with Alzheimer’s and 15 without, bound cGP was higher in the Alzheimer’s brains (Kang et al., 2021).
• Pregnancy, weight and breast milk (observational) — Six years after a first pregnancy, women with high blood pressure had lower blood cGP than control women (p = 0.043) (Guan et al., 2018). In 501 Finnish mothers, more cGP in breast milk went with lower infant weight over 5 years (p = 0.019) but higher BMI at age 5 (p = 0.021) (Galante et al., 2020).

The evidence meter on the Cyclic Glycine-Proline card reads “Animal only”: it counts published human data on cGP itself, for brain and nerve use. The NA-831 trial’s results come only from its sponsor, in abstracts and, per ADDF’s 2022 review, on its subsidiary’s website; the abstracts disagree with its registration on doses, size and who was enrolled and give no result on its main measure, though a 2025 one names it (NCT03538522; Tran et al., 2024, abstract e095627; Tran, 2025; ADDF, 2022); the two peer-reviewed human studies gave food-derived products, which contain other substances besides cGP, with no control group (Fan et al., 2018; Chen et al., 2025); and the rest of the human work measures cGP already in the body (Fan et al., 2019; Kang et al., 2021).

Reconstitution & Storage

There is nothing to reconstitute in any human use on record: the NA-831 trials registered capsules taken by mouth (NCT03538522; NCT04452565), the two peer-reviewed studies that gave a product gave capsules (Fan et al., 2018; Chen et al., 2025), and the supplement is sold as capsules (maker’s listings, read October 4, 2026). One registered Phase 1 listed an inhaled form, with no results (NCT04480333).

• Supplement capsules — The maker’s FAQ gives a three-year shelf life, with the expiry date on the bottle (maker’s FAQ, read October 4, 2026).
• Reagent powder — No label, trial record or published document read for this page gives reconstitution or storage directions for pure cGP powder, which chemical suppliers sell as a laboratory chemical (supplier catalogues, searched October 4, 2026).

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Side Effects & Risks

• In people — The sponsor’s abstract calls NA-831 “well-tolerated at 30 mg/day” with “no serious adverse events observed” (Tran et al., 2024, abstract e095627); the Alzheimer’s Drug Discovery Foundation notes that the abstracts leave unclear whether any adverse events were recorded, and of what kinds and rates (ADDF, 2022). In another of the sponsor’s 2024 abstracts, 12 of the 18 participants with diabetes among the 56 on NA-831 reported a loss of 17–23% of their body weight over 6 months, while a few of the 56 on placebo reported a loss of 3–5% (Tran et al., 2024, abstract e095715); the trial’s registration lists no weight measure (NCT03538522). The 2018 blackcurrant paper does not report on adverse events (Fan et al., 2018), and the 2025 diabetes study’s abstract does not mention them (Chen et al., 2025).
• IGF-1 works both ways — Its proposed action is on how much IGF-1 is free to act, and its own researchers write that “excessive IGF-1 contributes to growth of tumours” (Guan et al., 2014). In mice cGP slowed an IGF-1-secreting lymphoma, and in nursing rats it sped the shrinking of mammary tissue after weaning (Guan et al., 2014; Singh-Mallah et al., 2017). In two human cell lines it did not speed cell division (Zainullina et al., 2020). What months of use do to IGF-1-dependent tissues in people has not been studied.
• Saliva and opioid-like effects (mice) — Injected cGP reduced saliva flow in mice, as morphine did, and naloxone restored it (Melo et al., 2020); naloxone also reduced its pain relief (Ferro et al., 2015). Whether either happens in people is not known.
• Pregnancy, breastfeeding and children — Given to nursing rats, cGP passed into their milk and changed their mammary glands after weaning (Singh-Mallah et al., 2016; Singh-Mallah et al., 2017). No human study has tested it in pregnancy or breastfeeding (PubMed, searched October 4, 2026). The maker’s FAQ advises against its capsules in pregnancy or breastfeeding; it says it has not completed any formal trials in children but that some children with IGF-1-related genetic disorders “may benefit”, and its plain capsule, with no added extract, is described as supporting “healthy growth and development in children” (maker’s listings and FAQ, read October 4, 2026).
• What has not been tested — No toxicology study, drug-interaction study or long-term human safety study of cGP turned up on PubMed (searched October 4, 2026). The capsules on sale add other ingredients, and no independent analysis of a cGP product has been published.
• WADA — Cyclic glycine-proline is not named on the 2026 Prohibited List. Section S0 prohibits at all times substances not addressed elsewhere on the List “with no current approval by any governmental regulatory health authority for human therapeutic use (e.g. drugs under pre-clinical or clinical development or discontinued…)” (World Anti-Doping Agency, 2026). No approval of cGP as a medicine turned up for this page. S2.3 also prohibits IGF-1 and “other growth factors or growth factor modulators affecting … vascularisation … regenerative capacity”; WADA has not said whether it covers cGP, which its researchers describe as regulating IGF-1 (World Anti-Doping Agency, 2026; Guan et al., 2014). Under either section it is prohibited at all times. The List does not mention cGP or the ordinary foods that contain it, such as coffee, beef and blackcurrants (World Anti-Doping Agency, 2026; Hu et al., 2024).

Bloodwork & Monitoring

No monitoring guidance for cGP has been published outside the studies. The studies measured these:

• cGP, IGF-1 and IGFBP-3 in blood — cGP by the Auckland group’s own liquid chromatography–mass spectrometry method, IGF-1 and IGFBP-3 by commercial ELISA kits, and the cGP-to-IGF-1 molar ratio (Fan et al., 2019).
• Spinal fluid — cGP, IGF-1 and IGFBP-3 in fluid taken by lumbar puncture before and after the blackcurrant capsules (Fan et al., 2018).
• In the diabetes study — Foot sensation tests, blood pressure, fasting glucose and HbA1c at three hospital visits (ISRCTN84351085), with kidney function among the secondary outcomes (Chen et al., 2025).
• In the NA-831 Alzheimer’s trial — The Clinical Dementia Rating Sum of Boxes at 24 weeks as the registered main measure (NCT03538522); the sponsor’s abstract reports the ADAS-Cog-13 and CIBIC-Plus scales (Tran et al., 2024, abstract e095627).
• Which tests fit a given person — A question for a licensed healthcare provider. This page can’t answer it.

Commonly Stacked With

In registered trials its sponsor paired NA-831 with COVID-19 drugs (atazanavir, dexamethasone, inhaled remdesivir) and with the oral polio vaccine, none with results (NCT04452565; NCT04540185; NCT04480333), and a 2025 abstract describes a Phase 3, which it says is underway, testing it alone and with donanemab (Tran et al., 2025); the supplement’s maker sells one version with Bacopa monnieri extract (maker’s listings, read October 4, 2026). No study has tested cGP with any other compound on this site (PubMed and Europe PMC, searched October 4, 2026).

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References

1. National Library of Medicine. PubChem: Cyclo(prolylglycyl), CID 126154 (C7H10N2O2, 154.17 g/mol; (8aS)-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione; synonyms include cyclic glycine-proline, cycloprolylglycine, cyclo(Gly-Pro), NA-831 and traneurocin). pubchem.ncbi.nlm.nih.gov. Read October 4, 2026.
2. FDA. Global Substance Registration System: Cyclo(prolylglycyl), UNII W7O69J5F2B (C7H10N2O2; names include CGP, cyclic glycine-proline, NA-831, NA 831 [WHO-DD], NA831 and traneurocin). gsrs.ncats.nih.gov. Read October 4, 2026.
3. Guan J, Li F, Kang D, Anderson T, et al. Cyclic Glycine-Proline (cGP) Normalises Insulin-Like Growth Factor-1 (IGF-1) Function: Clinical Significance in the Ageing Brain and in Age-Related Neurological Conditions. Molecules. 2023;28(3):1021. PMID: 36770687. DOI: 10.3390/molecules28031021. (Full text at PMC9919809, read October 4, 2026: its conflicts-of-interest statement names Guan as an employee of the New Zealand company that sells cGP supplements, and its funding list includes that company under its current and earlier names.)
4. Guan J, Gluckman P, Yang P, Krissansen G, et al. Cyclic glycine-proline regulates IGF-1 homeostasis by altering the binding of IGFBP-3 to IGF-1. Sci Rep. 2014;4:4388. PMID: 24633053. DOI: 10.1038/srep04388.
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14. Sharonova IN, Bukanova YV, Gudasheva TA, Skrebitsky VG. Effect of Endogenous Neuropeptide Cycloprolylglycine on GABAA Receptors in Cerebellar Purkinje Cells. Bull Exp Biol Med. 2019;167(1):39-42. PMID: 31177457. DOI: 10.1007/s10517-019-04455-7.
15. Gudasheva TA, Povarnina PY, Koliasnikova KN, Alyaeva AG, et al. The Anxiolytic Effect of the Neuropeptide Cycloprolylglycine Is Mediated by AMPA and TrkB Receptors. Dokl Biochem Biophys. 2020;493(1):190-192. PMID: 32894462. DOI: 10.1134/S1607672920040067.
16. Abdullina AA, Vasileva EV, Kulikova EA, Naumenko VS, et al. The neuropeptide cycloprolylglycine produces antidepressant-like effect and enhances BDNF gene expression in the mice cortex. J Psychopharmacol. 2022;36(2):214-222. PMID: 35102783. DOI: 10.1177/02698811211069101.
17. Gudasheva TA, Koliasnikova KN, Alyaeva AG, Nikolaev SV, et al. Neuroprotective Effect of the Neuropeptide Cycloprolylglycine Depends on AMPA- and TrkB-Receptor Activation. Dokl Biochem Biophys. 2022;507(1):264-267. PMID: 36786983. DOI: 10.1134/S1607672922060047.
18. Zainullina LF, Ivanova TV, Gudasheva TA, Vakhitova YV, Seredenin SB. Effect of Neuropeptide Cyclo-L-Prolylglycine on Cell Proliferative Activity. Bull Exp Biol Med. 2020;169(3):347-350. PMID: 32737722. DOI: 10.1007/s10517-020-04884-9.
19. Boyko SS, Zherdev VP, Shevchenko RV. [Pharmacokinetics of noopept and its active metabolite cycloprolyl glycine in rats]. Biomed Khim. 2018;64(5):455-458. PMID: 30378564. DOI: 10.18097/PBMC20186405455. (In Russian, with an English abstract: noopept, N-phenylacetyl-prolyl-L-glycine ethyl ester, “was developed and introduced into medical practice” at the Zakusov Research Institute of Pharmacology.)
20. Singh-Mallah G, Singh K, McMahon CD, Harris P, et al. Maternally Administered Cyclic Glycine-Proline Increases Insulin-Like Growth Factor-1 Bioavailability and Novelty Recognition in Developing Offspring. Endocrinology. 2016;157(8):3130-3139. PMID: 27355491. DOI: 10.1210/en.2016-1189.
21. Singh-Mallah G, McMahon CD, Guan J, Singh K. Cyclic-glycine-proline accelerates mammary involution by promoting apoptosis and inhibiting IGF-1 function. J Cell Physiol. 2017;232(12):3369-3383. PMID: 28063218. DOI: 10.1002/jcp.25782.
22. Singh-Mallah G, Ardalan M, Kang D, Singh K, et al. Administration of cyclic glycine-proline during infancy improves adult spatial memory, astrocyte plasticity, vascularization and GluR-1 expression in rats. Nutr Neurosci. 2022;25(12):2517-2527. PMID: 34565308. DOI: 10.1080/1028415X.2021.1980845.
23. Li F, Liu K, Wang A, Harris PWR, et al. Cyclic glycine-proline administration normalizes high-fat diet-induced synaptophysin expression in obese rats. Neuropeptides. 2019;76:101935. PMID: 31146894. DOI: 10.1016/j.npep.2019.05.006.
24. Li F, Liu K, Gray C, Harris P, et al. Cyclic glycine-proline normalizes systolic blood pressure in high-fat diet-induced obese male rats. Nutr Metab Cardiovasc Dis. 2020;30(2):339-346. PMID: 31753784. DOI: 10.1016/j.numecd.2019.09.016.
25. Arora T, Sharma SK. Cyclic Glycine-Proline Improves Memory and Reduces Amyloid Plaque Load in APP/PS1 Transgenic Mouse Model of Alzheimer's Disease. Int J Alzheimers Dis. 2023;2023:1753791. PMID: 36909366. DOI: 10.1155/2023/1753791.
26. Kaneko H, Namihira M, Yamamoto S, Numata N, Hyodo K. Oral administration of cyclic glycyl-proline facilitates task learning in a rat stroke model. Behav Brain Res. 2022;417:113561. PMID: 34509530. DOI: 10.1016/j.bbr.2021.113561.
27. Murotomi K, Kagiwada H, Hirano K, Yamamoto S, et al. Cyclo-glycylproline attenuates hydrogen peroxide-induced cellular damage mediated by the MDM2-p53 pathway in human neural stem cells. J Cell Physiol. 2023;238(2):434-446. PMID: 36585955. DOI: 10.1002/jcp.30940.
28. Aguado-Llera D, Canelles S, Fernández-Mendívil C, Frago LM, et al. Improvement in inflammation is associated with the protective effect of Gly-Pro-Glu and cycloprolylglycine against Aβ-induced depletion of the hippocampal somatostatinergic system. Neuropharmacology. 2019;151:112-126. PMID: 30981749. DOI: 10.1016/j.neuropharm.2019.04.008.
29. Ferro JN, de Aquino FL, de Brito RG, dos Santos PL, et al. Cyclo-Gly-Pro, a cyclic dipeptide, attenuates nociceptive behaviour and inflammatory response in mice. Clin Exp Pharmacol Physiol. 2015;42(12):1287-1295. PMID: 26277051. DOI: 10.1111/1440-1681.12480.
30. Melo IS, Candeia-Medeiros N, Ferro JNS, Cavalcante-Araújo PM, et al. Restoration of Cyclo-Gly-Pro-induced salivary hyposecretion and submandibular composition by naloxone in mice. PLoS One. 2020;15(3):e0229761. PMID: 32155179. DOI: 10.1371/journal.pone.0229761.
31. Fan D, Krishnamurthi R, Harris P, Barber PA, Guan J. Plasma cyclic glycine proline/IGF-1 ratio predicts clinical outcome and recovery in stroke patients. Ann Clin Transl Neurol. 2019;6(4):669-677. PMID: 31019991. DOI: 10.1002/acn3.743. (Funding statement: Brain Research New Zealand, with co-funding from a New Zealand supplement company, the earlier name of the company that now sells cGP capsules.)
32. Fan D, Pitcher T, Dalrymple-Alford J, MacAskill M, et al. Changes of plasma cGP/IGF-1 molar ratio with age is associated with cognitive status of Parkinson disease. Alzheimers Dement (Amst). 2020;12(1):e12025. PMID: 32671179. DOI: 10.1002/dad2.12025.
33. Fan D, Alamri Y, Liu K, MacAskill M, et al. Supplementation of Blackcurrant Anthocyanins Increased Cyclic Glycine-Proline in the Cerebrospinal Fluid of Parkinson Patients: Potential Treatment to Improve Insulin-Like Growth Factor-1 Function. Nutrients. 2018;10(6):714. PMID: 29865234. DOI: 10.3390/nu10060714.
34. Alamri Y. The use of dietary supplements and perceived quality of life in patients with Parkinson's disease. J Clin Neurosci. 2018;56:137-138. PMID: 29958758. DOI: 10.1016/j.jocn.2018.06.029.
35. Guan J, Singh-Mallah G, Liu K, Thorstensen E, et al. The role for cyclic Glycine-Proline, a biological regulator of insulin-like growth factor-1 in pregnancy-related obesity and weight changes. J Biol Regul Homeost Agents. 2018;32(3):465-478. PMID: 29921371.
36. Kang D, Waldvogel HJ, Wang A, Fan D, et al. The autocrine regulation of insulin-like growth factor-1 in human brain of Alzheimer's disease. Psychoneuroendocrinology. 2021;127:105191. PMID: 33706042. DOI: 10.1016/j.psyneuen.2021.105191.
37. Galante L, Pundir S, Lagström H, Rautava S, et al. Growth Factor Concentrations in Human Milk Are Associated With Infant Weight and BMI From Birth to 5 Years. Front Nutr. 2020;7:110. PMID: 32850934. DOI: 10.3389/fnut.2020.00110.
38. Chen L, Huang L, Zhang H, Chen Q, et al. Natural cyclic glycine-proline supplementation improves clinical outcomes of vascular complications in patients with type-2 diabetes mellitus: An exploratory study. J Funct Foods. 2025;133:106982. DOI: 10.1016/j.jff.2025.106982. (Not in PubMed; abstract read through OpenAlex, October 4, 2026.)
39. ISRCTN registry. Can a dietary supplement providing natural cGP (cyclic Glycine-Proline) compliment the body’s own internal levels of cGP and help improve the metabolic health of type 2 diabetes sufferers and aid in the recovery of complications associated with metabolic syndrome. ISRCTN84351085: two-armed, open-label, non-randomised; 38 participants aged 45–80; 20–25 µg or 40–45 µg natural cGP a day for 6 months; Tianyou Hospital, Wuhan; co-funded by the Health Commission of Hubei Province and a New Zealand cGP supplement company. isrctn.com (API record). Read October 4, 2026.
40. ClinicalTrials.gov. Registrations of NA-831 (traneurocin), sponsor Biomed Industries, Inc.: NCT03538522 (Phase 2, mild cognitive impairment due to Alzheimer’s disease, 10, 20 or 40 mg once a day for 24 weeks, 126 enrolled, completed 2019, main measure CDR-SB at week 24), NCT04452565 (Phase 2/3, COVID-19, 525 planned, status unknown), NCT04540185 (Phase 3, COVID-19 with oral polio vaccine, 3,600 planned, status unknown) and NCT04480333 (Phase 1, inhaled with remdesivir, 45 planned, status unknown). None posts results. clinicaltrials.gov, API v2. Read October 4, 2026.
41. ClinicalTrials.gov. NCT07572240: an industry-sponsored, randomized, open-label comparison of two doses of a bovine collagen-peptide supplement (one or three 1 g tablets once a day for 56 days) in 72 stressed but otherwise healthy adults aged 35–70; change in blood cGP is among its other measures, and the record does not say the product contains cGP; active, not recruiting; primary completion estimated November 2026. clinicaltrials.gov, API v2. Read October 5, 2026.
42. Tran L, Tran ZV, Vu F. Phase 2 Clinical Trials of NA‐831 for the Treatment of Alzheimer’s Disease and Major Depressive Disorder, support the Neurogenesis Hypothesis. Alzheimers Dement. 2024;20(Suppl 8):e095627. DOI: 10.1002/alz.095627. PMCID: PMC11712904. (Conference abstract, cited as Tran et al., 2024, abstract e095627; authors from Biomed AI, Inc. and Biomed Industries, Inc.)
43. Tran L, Tran ZV, Vu F. Associations Between Alzheimer’s Disease and Obesity: Clinical Trials of NA‐831 for AD and NA‐931 for Obesity. Alzheimers Dement. 2024;20(Suppl 8):e095715. DOI: 10.1002/alz.095715. PMCID: PMC11712949. (Conference abstract, cited as Tran et al., 2024, abstract e095715; authors from Biomed Industries, Inc.)
44. Tran L, Tran ZV, Vu F. Phase 3 Clinical Protocol: Placebo‐Controlled, Double‐Blind, Parallel‐Group to Study Safety and Efficacy of NA‐831 in Combination with Lecanemab in Subjects with Early Alzheimer’s Disease. Alzheimers Dement. 2024;20(Suppl 8):e095755. DOI: 10.1002/alz.095755. PMCID: PMC11714023. (Conference abstract, cited as Tran et al., 2024, abstract e095755.)
45. Tran L. Neuro‐Metabolic Association in Alzheimer’s Disease and Obesity: Clinical Evaluation of NA‐831 and NA‐931. Alzheimers Dement. 2025;21(Suppl 7):e108265. DOI: 10.1002/alz70861_108265. PMCID: PMC12725039. (Conference abstract, cited as Tran, 2025; it names NCT03538522 as the trial of 112 participants given 10 or 30 mg a day; author from Biomed Industries, Inc.)
46. Tran L, Vu F, Tran ZV. A Phase 3 Clinical Protocol: Placebo‐Controlled, Double‐Blind, Parallel‐Group to Study the Safety and Efficacy of NA‐831 in Combination with Donanemab in Subjects with Early Alzheimer's Disease. Alzheimers Dement. 2025;21(Suppl 7):e108266. DOI: 10.1002/alz70861_108266. PMCID: PMC12725387. (Conference abstract, cited as Tran et al., 2025.)
47. Alzheimer’s Drug Discovery Foundation (ADDF). Cognitive Vitality Report: Traneurocin (NA-831). Last updated September 29, 2022. alzdiscovery.org/uploads/cognitive_vitality_media/Traneurocin_(NA-831).pdf. Read October 4, 2026.
48. Neumeyer AM, Srivastava S, Holder JL, Milad MA, et al. NNZ-2591 in Children and Adolescents With Phelan-McDermid Syndrome: Single-Group, Open-Label, Phase 2 Trial Results. Neurol Genet. 2026;12(1):e200338. PMID: 41450730. DOI: 10.1212/NXG.0000000000200338. (Erratum: Neurol Genet. 2026;12(4):e200405.)
49. Neul JL, Percy AK, Benke TA, Berry-Kravis EM, et al. Design and outcome measures of LAVENDER, a phase 3 study of trofinetide for Rett syndrome. Contemp Clin Trials. 2022;114:106704. PMID: 35149233. DOI: 10.1016/j.cct.2022.106704.
50. Acadia Pharmaceuticals Inc. Daybue (trofinetide) oral solution and Daybue Stix prescribing information. DailyMed set ID 67e6f2d9-21f6-466f-9def-826c6a4b8257 (version effective September 4, 2026); Drugs@FDA NDA 217026 (Daybue, original approval March 10, 2023) and NDA 219884 (Daybue Stix, approved December 11, 2025). Read October 4 and 5, 2026.
51. Product listings and FAQ of a New Zealand cGP supplement maker (capsules of blackcurrant fruit powder and hydrolysed collagen standardized to 40 µg of cGP; one listing’s directions: adults, one capsule a day, at least 90 days; three-year shelf life; not advised in pregnancy or breastfeeding; no completed formal trials in children; sold online with international shipping and through selected stockists in New Zealand). Read October 4, 2026 (maker not named, by site rule).
52. FDA. Drugs@FDA through openFDA (api.fda.gov/drug/drugsfda.json): searches for cyclo(prolylglycyl), cyclic glycine-proline, cycloprolylglycine, glycylproline, NA-831 and traneurocin, October 4, 2026 (no records). European Medicines Agency. Medicines data table (ema.europa.eu, medicines-output-medicines_json-report), searched for the same names, October 4, 2026 (no entry).
53. Code of Federal Regulations. 21 CFR 216.23, Bulk drug substances that can be used to compound drug products in accordance with section 503A of the Federal Food, Drug, and Cosmetic Act, and 216.24, Drug products withdrawn or removed from the market for reasons of safety or effectiveness. ecfr.gov. Read October 4, 2026.
54. FDA. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act (categories 1–3). Updated May 14, 2026. fda.gov/media/94155/download.
55. FDA. Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act (categories 1–3). Updated March 21, 2025. fda.gov/media/94164/download.
56. World Anti-Doping Agency. Prohibited List 2026 (in effect January 1, 2026). S0, Non-approved substances; S2.3, Growth factors and growth factor modulators. wada-ama.org.
57. Searches of October 4, 2026: PubMed, “cyclic glycine-proline” OR “cyclic glycine proline” OR cycloprolylglycine OR “cyclo-prolylglycine” OR “cyclo-L-prolylglycine” OR “cyclo-prolyl-glycine” OR “cycloprolyl-glycine” OR “cyclic glycyl-proline” OR “cyclic glycylproline” OR “cyclo-glycylproline” OR “Cyclo-Gly-Pro” OR traneurocin (95 records; about half test or measure cGP in cells, animals or people; adding the spellings “cyclo(Gly-Pro)” and “cyclo(Pro-Gly)” gives 118, re-run October 5, 2026: of the 23 added records, nine are on larger rings such as cyclo(Pro-Gly)3, and several report it among compounds made by microbes); PubMed, “NA-831,” “NA 831” and “NA831” in titles and abstracts (no records), and “traneurocin” in titles and abstracts (no records, October 5, 2026; a plain search for traneurocin returns 30 records, mapped by PubMed to cyclo(prolylglycyl)); PubMed and Europe PMC, cGP’s names with noopept, Semax, Selank, Cerebrolysin, IGF-1 LR3, MGF, BPC-157 or dihexa (no study of a combination), and with toxicology, drug-interaction and pregnancy terms (no such study of cGP); Europe PMC, NA-831 and traneurocin in titles (eight conference abstracts from the sponsor, no full paper); ClinicalTrials.gov, “cyclic glycine proline,” “cycloprolylglycine,” “NA-831,” “traneurocin” and “Biomed Industries” (four NA-831 registrations, none recruiting or active; “cyclic glycine proline” also returns NCT07572240, an active study of a collagen-peptide supplement, and NCT07365514, a recruiting trial of blackcurrant extract, both of which measure blood cGP, re-run October 5, 2026); ISRCTN (ISRCTN84351085); NIH Dietary Supplement Label Database, “cyclic glycine-proline,” “cyclo(gly-pro)” and “cycloprolylglycine” (no labels); web searches for supplement and reagent listings (sellers not named).

Related Research

• NoopeptRussian proline-glycine memory drug; turns partly into cGP in rats
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• IGF-1 LR3Long-acting lab-made IGF-1 analogue
• CerebrolysinPig-brain peptide mixture for stroke recovery