Thymoctonan
Thymic humoral factor gamma 2: an eight-amino-acid thymus peptide that boosted T cells in mice and did little against hepatitis D
Thymoctonan is the international name for thymic humoral factor gamma 2 (THF-gamma 2), an eight-amino-acid peptide purified from calf thymus in 1988 and then made synthetically. In mice it restored T-cell function weakened by age, infection or chemotherapy. Its one published trial in people, in 11 adults with chronic hepatitis D, found limited effect, and in human blood the peptide is broken down within minutes. It was never approved.
Used in human trials: 40 mcg, daily for 15 days, then twice weekly for 22 weeks, intramuscular (Studied dose) Details ↓
Recommended Dosing
Used in human trials
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
What is it?
Thymoctonan is the international nonproprietary name for thymic humoral factor gamma 2, usually written THF-gamma 2. In 1988 researchers purified it from calf thymus by following the activity of a cruder thymus extract through a series of separation steps. A tonne of thymus gave about five micrograms. The pure peptide turned out to be eight amino acids long, Leu-Glu-Asp-Gly-Pro-Lys-Phe-Leu, with no resemblance to other thymic hormones such as thymosin or thymulin, and a synthetic copy behaved exactly like the natural one. The authors reported that it carried essentially all the activity of the extract it came from, which is not the same thing as the extract: the older 'thymic humoral factor' studies used the crude mixture and are not about this molecule.
Most of what is known comes from mice. At nanogram doses it restored T-cell responses and the production of the growth factor interleukin-2 in ageing mice, more efficiently per dose than thymosin alpha-1 in one comparison. Given after chemotherapy, it repaired damaged T-cell populations in mice treated for plasmacytoma, and with chemotherapy it reduced lung metastases and lengthened survival in mice with Lewis lung carcinoma, even when given through the nose. Donor mice treated with it supplied immune cells that better protected other mice against a fatal cytomegalovirus infection. In human cells it raised interleukin-2 output by blood cells from people with chronic hepatitis B and helped bone-marrow progenitor cells grow in culture.
Those findings led to one small trial. In a 2002 pilot study, hepatologists gave 40 micrograms into the muscle daily for 15 days and then twice weekly for 22 weeks to adults with chronic hepatitis D. Of eight patients with virus in their blood at the start, three cleared it during treatment, but it returned in nearly everyone after the course ended, and liver enzymes did not normalise in anyone. The authors judged its effect limited and suggested higher doses or combinations; no later trial appears in PubMed.
Part of the problem may be chemistry. Enzymes in blood trim amino acids off the front of the peptide and cut it between lysine and phenylalanine; angiotensin-converting enzyme and neutral endopeptidase both do this. A 2020 study measured a half-life of under six minutes in human, rat and mouse whole blood. Thymoctonan has no FDA or EMA approval, and its research record is mostly from the late 1980s and 1990s.
At a Glance
Every value in this table is printed from the Grey Peptides dataset, the same record the compound explorer and comparison tool read, so the three can never disagree.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Published Research
These are the studies of thymic humoral factor gamma 2 read from their PubMed abstracts on October 29, 2026: one trial in people, seven studies in human blood, cells or enzymes, four in mice and one review. Studies of the older crude thymus extract called thymic humoral factor, and of analogues with a changed seventh amino acid, are different substances and are not carded.
Chronic hepatitis D: 11 adults
Patients received 40 micrograms into the muscle for 15 consecutive days and then twice weekly for 22 more weeks. Hepatitis D RNA became undetectable during treatment in 3 of 8 who had it, but relapsed in all except two during follow-up. Liver enzyme levels did not change significantly, and the authors call the efficacy limited at the doses given.
Purification and sequence
The octapeptide was isolated from calf thymus, about 5 micrograms per tonne of tissue, and sequenced as Leu-Glu-Asp-Gly-Pro-Lys-Phe-Leu. It increased lymphocyte proliferation and interleukin-2 production at 5 ng per ml in cells and 10 ng per kg in mice, and a synthetic copy had identical activity.
Broken down in blood within minutes
In whole blood from people, rats and mice at body temperature, the intact peptide had a half-life under six minutes. Aminopeptidases removed residues one by one from the front end, while a separate endopeptidase cut the Lys-Phe bond; breakdown was fastest in rat blood.
Angiotensin-converting enzyme cuts it
Human plasma degraded the peptide in two independent steps: removal of the first leucine and cleavage between lysine 6 and phenylalanine 7. The second step was carried out by angiotensin-converting enzyme, and inhibitors of aminopeptidases and of that enzyme blocked breakdown completely.
Neutral endopeptidase cuts it too
Neutral endopeptidase, an enzyme on immune and bone-marrow cells, rapidly split the Lys6-Phe7 bond, as efficiently as it cleaves enkephalin; the inhibitor phosphoramidon prevented the cut.
Blood cells from hepatitis B carriers
On its own it had no effect on blood mononuclear cells, but with a low dose of a mitogen it increased interleukin-2 output, significantly so at 150 ng per ml in patients with chronic hepatitis B, and tumour necrosis factor alpha in patients and controls. Interferon gamma did not change.
Human bone-marrow progenitor cells
With growth factors present, it raised the growth of myeloid and red-cell progenitor colonies from the bone marrow and blood of healthy donors two- to two-and-a-half-fold. Cells from severely suppressed marrow barely responded; an antiserum against the peptide reversed the effect.
Umbilical cord blood lymphocytes
Preincubation raised the share of cord blood lymphocytes carrying CD4 or CD8 without changing CD3, and increased interleukin-2 activity after mitogen stimulation, with an optimum at 300 to 600 ng per ml.
T cells in ageing mice
A single injection of a few nanograms restored mitogen-responsive and cytokine-producing T cells in the thymus and spleen of immunodeficient old mice to young levels. For helper activity it was 400 times as efficient per dose as thymosin alpha-1.
Cytomegalovirus infection in mice
Spleen cells from donor mice treated with the peptide protected immunosuppressed mice against a fatal murine cytomegalovirus infection far better than cells from untreated donors. Treatment restored the CD4 and CD8 T cells that the infection had depleted.
Mice after cancer chemotherapy
Mice cured of plasmacytoma with melphalan were left with weakened T-cell function. Treatment with the synthetic peptide restored T-cell subsets, antibody and allogeneic responses, and raised interleukin-2 production above normal.
Lung metastases, given through the nose
In mice with highly metastatic Lewis lung carcinoma, intranasal THF-gamma 2 after a single dose of chemotherapy reduced lung metastatic load, prolonged survival and restored impaired immune measures compared with chemotherapy alone.
Thymic hormones, with a focus on THF-gamma 2
A review of thymic hormones and factors, from crude extracts to synthetic peptides, giving special attention to THF-gamma 2 and to clinical trials of thymic factors in immune deficiency, viral infection and cancer; the authors conclude more research is needed to define their use.
Side Effects & Contraindications
Reported Side Effects
From the one human trial, which reports little on safety.
Contraindications & Cautions
No product label exists. These cautions follow from the evidence.
Legal Status
Thymoctonan was never approved as a medicine.
Frequently Asked Questions
?What is thymoctonan?
The international name for thymic humoral factor gamma 2, an eight-amino-acid peptide (Leu-Glu-Asp-Gly-Pro-Lys-Phe-Leu) purified from calf thymus in 1988 and later made synthetically.
?Is it the same as thymic humoral factor?
No. Thymic humoral factor was a crude calf-thymus extract studied in the 1970s and 1980s. Thymoctonan is the single peptide purified from it, and studies of the extract are not studies of this molecule.
?Has it been tested in people?
In one published pilot study: 11 adults with chronic hepatitis D received 40 micrograms into the muscle for about six months. It cleared the virus temporarily in three of eight, and the authors called the effect limited.
?How long does it last in the body?
In human whole blood at body temperature, the intact peptide had a half-life under six minutes; enzymes including angiotensin-converting enzyme break it down.
References
- [other] PubChem CID 9897695, Thymoctonan: formula C43H67N9O13, molecular weight 918.0. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/9897695
- [clinical-trial] Rosina F, et al. "Treatment of chronic hepatitis D with thymus-derived polypeptide thymic humoral factor-gamma 2: a pilot study." Dig Liver Dis, 2002;34(4):285-9. PMID: 12038813.
- [pubmed] Burstein Y, et al. "Thymic humoral factor gamma 2: purification and amino acid sequence of an immunoregulatory peptide from calf thymus." Biochemistry, 1988;27(11):4066-71. PMID: 3261994.
- [pubmed] Martignoni M, et al. "Degradation of thymic humoral factor γ2 in human, rat and mouse blood: An experimental and theoretical study." Biochim Biophys Acta Proteins Proteom, 2020;1868(9):140467. PMID: 32512181.
- [pubmed] Bramucci M, et al. "Degradation of thymic humoral factor gamma2 by human plasma: involvement of angiotensin converting enzyme." Regul Pept, 2003;111(1-3):199-205. PMID: 12609769.
- [pubmed] Indig FE, et al. "Hydrolysis of thymic humoral factor gamma 2 by neutral endopeptidase (EC 3.4.24.11)." Biochem J, 1991;278 ( Pt 3)(Pt 3):891-4. PMID: 1898375.
- [pubmed] Daniels HM, et al. "THF gamma 2 stimulates cytokine release by peripheral blood mononuclear cells of patients with chronic hepatitis B virus infection." J Hepatol, 1994;20(3):370-5. PMID: 7516950.
- [pubmed] Barak Y, et al. "Thymic humoral factor-gamma 2, an immunoregulatory peptide, enhances human hematopoietic progenitor cell growth." Exp Hematol, 1992;20(2):173-7. PMID: 1544385.
- [pubmed] Ben-Hur H, et al. "Immune modulation exerted by thymic humoral factor (THF-gamma 2), on T-cell subsets and IL-2 production of umbilical cord blood lymphocytes." Immunopharmacol Immunotoxicol, 1990;12(1):123-33. PMID: 2112568.
- [pubmed] Goso C, et al. "Effect of synthetic thymic humoral factor (THF-gamma 2) on T cell activities in immunodeficient ageing mice." Clin Exp Immunol, 1992;87(3):346-51. PMID: 1531947.
- [pubmed] Rager-Zisman B, et al. "Thymic humoral factor, THF-gamma 2, enhances immunotherapy of murine cytomegalovirus (MCMV) infection by both CD4+ and CD8+ immune T cells." Immunol Lett, 1993;39(1):23-31. PMID: 7908278.
- [pubmed] Ophir R, et al. "A synthetic thymic hormone, THF-gamma 2, repairs immunodeficiency of mice cured of plasmacytoma by melphalan." Int J Cancer, 1990;45(6):1190-4. PMID: 2141006.
- [pubmed] Rashid G, et al. "Inhibition of murine Lewis lung carcinoma metastases by combined chemotherapy and intranasal THF-gamma 2 immunotherapy." J Immunother Emphasis Tumor Immunol, 1996;19(5):324-33. PMID: 8941872.
- [review] Ben-Efraim S, et al. "Immunopotentiating and immunotherapeutic effects of thymic hormones and factors with special emphasis on thymic humoral factor THF-gamma2." Crit Rev Immunol, 1999;19(4):261-84. PMID: 10530429.
Sources & Citations
Studies were read from their PubMed records on October 29, 2026. Regulatory status comes from Drugs@FDA, the EMA medicines list and ClinicalTrials.gov, searched October 28, 2026. Grey Peptides sells nothing and links to no vendor.
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