Thymodepressin
Gamma-D-glutamyl-D-tryptophan, the mirror-image twin of thymogen, registered in Russia as an immunosuppressant and studied mostly in mice
Thymodepressin (INN orilotimod) is a two-amino-acid peptide built from the D-forms of glutamic acid and tryptophan. Its L-form relative, thymogen, stimulates immune cells; thymodepressin was found to do the opposite, damping the division of blood-forming cells and the activity of lymphocytes. It was registered in Russia in 2008 as an injection and nasal drops for autoimmune cytopenias, connective-tissue disease and psoriasis, and to protect bone marrow during chemotherapy. Its published human evidence is three small Russian studies without control groups; most of what is known comes from mouse experiments by its developers' circle.
Manufacturer's recommended dosing (Russian label): 1-2 mg (1-2 mL of the 0.1% solution), Once a day, Intramuscular Details ↓
Recommended Dosing
Manufacturer's recommended dosing (Russian label)
From the prescribing information. Other doses studied, if any, are in the full dosing data below.
Used in human trials
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
Work out syringe units → · New to syringes? · All dosing data ↓
What is it?
Thymodepressin came out of work on thymogen, the dipeptide L-glutamyl-L-tryptophan that Soviet researchers isolated from calf thymus and developed into an immunostimulant. While testing dozens of variants of thymogen, its developers swapped both amino acids for their D-forms, the mirror-image versions that the body's enzymes handle poorly. They expected the mirror-image peptides to be inactive. Instead, both D,D versions suppressed the same cell response that thymogen boosts. The developers' 2021 review says they had found no other case in the literature of enantiomers with opposite effects, apart from a few ion-carrying antibiotics. The gamma-linked D,D form became thymodepressin, and the same review reports that it was registered as a drug in Russia in 2008.
The Russian product information, as summarised on the Vidal.ru drug reference, matches that history: two registrations dated March 14, 2008 cover a 1 mg/mL (0.1%) solution for intramuscular injection and the same solution as nasal drops. The listed uses are conditions with an overactive immune response, namely autoimmune cytopenias (one, two or all three blood cell lines) and hypoplastic anaemias, systemic connective-tissue disease including rheumatoid arthritis, and psoriasis, plus protection of blood-forming stem cells during cytostatic chemotherapy. Vidal.ru marks both registrations as expired, with validity ending December 31, 2025, and its text was last updated in 2009, so whether the drug is still sold in Russia could not be confirmed. It has never been approved by the FDA or the European Medicines Agency.
In mice, its main target appears to be the blood-forming tissue rather than mature immune cells. It reduced the share of marrow stem cells in the dividing phase of the cell cycle, which shielded them from radiation and from heat, helped transplanted marrow take, and kept CD34+ precursor cells anchored in the marrow instead of moving into the blood, including in mice with tumours. A two-year study in rats and mice found no increase in tumours. In a mouse model of mercury-induced autoimmunity, the developers report that it lowered autoantibodies whether given before or after the disease developed, while cyclosporin A worked only when given beforehand.
The human record is thin. Two Russian studies took skin biopsies from people with atopic dermatitis, and later lichen planus, before and after two 10-day courses of injections, and found fewer dividing skin cells and clinical improvement. A third gave it to 22 people with autoimmune cytopenia and reported higher haemoglobin or platelet counts and fewer activated lymphocytes. None had a control group, none has been repeated outside Russia, and the psoriasis use listed in the Russian product information has no study on PubMed. A US or European reader should treat it as a regionally registered drug with early-stage evidence, not as an established immunosuppressant.
Mechanism of Action
How thymodepressin works at the molecular level is not known. The studies describe effects on blood-forming cells and lymphocytes, mostly in mice, and its developers say its targets remain to be found.
Slowing blood-forming cells
In mice it lowered the share of marrow stem cells that were dividing and kept CD34+ precursors in the marrow, with less CXCR4 and more integrin beta1 on the cells; the developers describe the effect as reversible and regulatory rather than toxic.
The opposite of thymogen
It is the D,D mirror image of thymogen's two amino acids, joined through the side-chain carboxyl. In the test used to screen thymogen variants, the L,L form stimulated thymocytes and the D,D forms inhibited them.
Published Research
These are the studies of thymodepressin read from their PubMed abstracts on October 29, 2026, with the full text of the 2021 review: three uncontrolled studies in patients, one study of donated human blood cells, six mouse and rat studies and two reviews by its developers. Almost every paper comes from a small group of Russian laboratories that includes the peptide's inventor, so none of it is independent replication.
Autoimmune cytopenia: 22 patients
Twenty-two patients with autoimmune blood disorders were treated with thymodepressin. Haemoglobin rose in those with autoimmune haemolytic anaemia and platelet counts rose in those with immune thrombocytopenic purpura, while total lymphocytes and activated CD3+CD69+ T cells fell. The authors describe it as safe, non-toxic and non-allergenic, usable by injection or nasally; the abstract reports no control group and no amounts.
Atopic dermatitis: dividing skin cells
Skin biopsies from people with atopic dermatitis showed far more dividing (Ki-67-positive) keratinocytes than normal skin, about 32% against 9%. After two 10-day courses of 1 mL of a 0.1% solution by intramuscular injection over 30 days the share fell to about 21%, and itching, redness, scaling and sleep improved. The abstract compares patients only with normal skin and their own baseline.
Atopic dermatitis and lichen planus
Biopsies from patients with atopic dermatitis and with lichen planus had raised Ki-67 indices (28.4% and 32.6%, against 8.65% in reference skin) and signs of local oxidative stress. After the same two 10-day courses of injections (0.1%, 1.0 mL) over 30 days, the indices fell to 17.0% and 10.9%. There was no untreated comparison group.
Donor blood phagocytes
Added to blood cells from healthy donors at 10 mM, thymogen, neogen and thymodepressin each increased the engulfing activity of neutrophils (not monocytes) and their output of reactive oxygen. Thymodepressin raised the neutrophils' hydrogen-peroxide signal by about 60%, so in this test the immunosuppressant stimulated rather than suppressed these cells.
Stem cells held in the marrow
In mice, with and without the stem-cell mobiliser G-CSF, thymodepressin lowered the number of CD34+ blood-forming cells in the blood and raised the share of marrow cells binding fibronectin and carrying integrin beta1, the authors' explanation being that it slows the cells' exit from the marrow.
Stem-cell traffic in tumour-bearing mice
In mice with growing tumours, treated animals had fewer CD34+ precursors in the blood throughout and two to three times fewer in the tumour, with more held in the marrow. Cells carrying the CXCR4 homing receptor fell in blood, marrow and tumour, while marrow cells carrying integrin beta1 and binding fibronectin roughly doubled.
Better take of marrow transplants
Given to recipient mice three times in the two days before irradiation and bone-marrow transplantation, it increased the colonies formed by donor stem cells; with marrow from a genetically different donor, nine-day spleen colonies rose about five-fold over controls.
Shielding marrow from radiation
Thymodepressin reduced the fraction of mouse marrow stem cells (CFU-S) in the S phase of the cycle. Given two days before 4 Gy of radiation, it was followed by three to five times better recovery of these cells than radiation alone, which the authors attribute to fewer cells being caught while dividing.
Shielding marrow from heat
Injected into donor mice or added to their marrow cells, it made stem cells more resistant to heating at 43 degrees C, while two tumour cell lines (EL-4 and Rauscher leukaemia) became more heat-sensitive after exposure.
Two-year cancer test in rats and mice
Rats and mice injected under the skin with 0.0145 or 0.145 mg/kg for 104 weeks had tumour rates no different from controls, and the authors conclude it is not carcinogenic in these species.
Its developers' review, with a cyclosporin comparison
The developers trace its accidental discovery, report its 2008 Russian registration and its use in autoimmune and allergic disease, and add mouse experiments. In mercury-induced autoimmunity it lowered anti-fibrillarin antibodies at 0.14-0.7 mg/kg both before and after the disease set in, while cyclosporin A worked only preventively and was lethal at its highest dose; in a graft-versus-host model it suppressed spleen enlargement by 70.7% against 34.6% for cyclosporin A.
Mirror-image peptides with opposite effects
The same group presents thymogen (L-Glu-L-Trp) and thymodepressin (D-Glu(D-Trp)) as the first example of two enantiomeric drugs that push immune balance in opposite directions, and discusses what this means for designing peptides that resist breakdown by switching their chirality.
Dosing Data
The first two rows are the regimen in the Russian product information for the 2008 registrations, as summarised on Vidal.ru; the regulator's own register could not be read, and Vidal.ru marks both registrations as expired. The other rows are what the two dermatology studies gave, as their abstracts state it.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or 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.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Thymodepressin is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
Unknown: we hold no copy of the preparation section of the label behind Thymodepressin's dose. Its label, named in Recommended Dosing above, is the source; the reconstitution calculator does the arithmetic for any vial.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Thymodepressin, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Thymodepressin stays intact once mixed.
How it is taken
As the approved label gives it: Intramuscular (Once a day; Russian label: 0.1% solution for injection (registration of March 14, 2008, marked expired)); Intranasal (Once a day; Russian label: 0.1% nasal drops (registration of March 14, 2008, marked expired)).
Source: Manufacturer's recommended dosing (Russian label): the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: not established by a measurement cited on this entry.
How long the doses were given: Russian label: 0.1% solution for injection (registration of March 14, 2008, marked expired): 7 days; repeated after a 7-day break if needed; Russian label: 0.1% nasal drops (registration of March 14, 2008, marked expired): 7 days, with week-long breaks between courses.
When effects appear: unknown; no source on this page gives a time to effect for Thymodepressin. Results reported in the studies are under Published Research.
Source: Manufacturer's recommended dosing (Russian label), the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: Allergic reactions (product information); A temporary fall in white blood cells that the product information says resolves as treatment continues; No toxicity or allergy reported in the cytopenia study, according to its authors; No increase in tumours in a two-year rat and mouse study. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Thymodepressin. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the Russian product information as summarised on Vidal.ru and the studies above, which report little on safety”).
Interactions
Unknown: a PubMed search for human interaction studies of Thymodepressin (reviewed 2026-10-28) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Thymodepressin products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder; it checks the measured mass against Thymodepressin's expected mass, 333.3 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Not FDA Approved. Elsewhere: approved in Russia (registered 2008; Vidal.ru marks the registration expired). Sport: Unsettled (S0 may apply).
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
From the Russian product information as summarised on Vidal.ru and the studies above, which report little on safety.
Contraindications & Cautions
The Russian product information as summarised on Vidal.ru lists these; the last two follow from the evidence.
Legal Status
Thymodepressin was registered as a medicine in Russia and has never been approved in the US or the EU.
Frequently Asked Questions
?What is thymodepressin?
A synthetic dipeptide, gamma-D-glutamyl-D-tryptophan (INN orilotimod), made from the mirror-image forms of the two amino acids in the immunostimulant thymogen. It suppresses immune and blood-forming cells instead of stimulating them.
?Is it approved for psoriasis?
In Russia, psoriasis is one of the listed uses in the product information for its 2008 registrations, alongside autoimmune cytopenias, connective-tissue disease and protection of bone marrow during chemotherapy. No study of it in psoriasis is indexed on PubMed, and it is not approved in the US or EU.
?How strong is the evidence in people?
Weak. Three small Russian studies, in atopic dermatitis, lichen planus and autoimmune cytopenia, report improvement, but none had a control group and none has been repeated elsewhere.
?How is it given?
As a 1 mg/mL solution, injected into a muscle or dropped into the nose. The Russian product information gives 1-2 mL a day for seven days by injection, or 1 mL a day for seven days by nose, with breaks between courses.
?How does it relate to thymogen?
Thymogen is L-glutamyl-L-tryptophan, an immunostimulant. Thymodepressin uses the D-forms of the same two amino acids, linked through glutamic acid's side chain, and in its developers' tests it has the opposite effect.
References
- [other] PubChem CID 7275810, Thymodepressin (orilotimod, D-gamma-glutamyl-D-tryptophan): formula C16H19N3O5, molecular weight 333.34. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/7275810
- [other] Vidal.ru drug reference, Thymodepressin (Тимодепрессин), read October 29, 2026: 0.1% (1 mg/mL) solution for intramuscular injection, Russian registration P N000022/04 of March 14, 2008, and nasal drops, registration P N000022/03 of March 14, 2008, both marked expired with validity ended December 31, 2025; active substance sodium gamma-D-glutamyl-D-tryptophan; ATC L04AA; indications, regimen, contraindications and side effects as listed (page last updated May 8, 2009). https://www.vidal.ru/drugs/thymodepressin__6921 and https://www.vidal.ru/drugs/thymodepressin__6922
- [clinical-trial] Vinogradova IuE, et al. "[Use of thymodepressin for treating autoimmune cytopenia]." Ter Arkh, 2002;74(8):64-7. PMID: 12360601.
- [clinical-trial] Sapuntsova SG, et al. "Proliferative processes in the epidermis of patients with atopic dermatitis treated with thymodepressin." Bull Exp Biol Med, 2002;133(5):488-90. PMID: 12420069.
- [clinical-trial] Sapuntsova SG, et al. "Status of free-radical oxidation and proliferation processes in patients with atopic dermatitis and lichen planus." Bull Exp Biol Med, 2011;150(6):690-2. PMID: 22235418.
- [pubmed] Dambaeva SV, et al. "[Effect of thymic peptides on the functional activity of phagocytic cells of donor peripheral blood]." Zh Mikrobiol Epidemiol Immunobiol, 2002:55-9. PMID: 12506630.
- [pubmed] Semina OV, et al. "Thymodepressin inhibits migration of CD34+ cells from bone marrow in normal and granulocyte CSF-stimulated hemopoiesis." Bull Exp Biol Med, 2007;144(6):831-4. PMID: 18856212.
- [pubmed] Semina OV, et al. "Dipeptide gamma-d-Glu-d-Trp (thymodepressin) inhibits migration of CD34+ cells from the bone marrow into peripheral blood during tumor growth." Bull Exp Biol Med, 2008;146(1):96-9. PMID: 19145362.
- [pubmed] Semina OV, et al. "Synthetic peptide thymodepressin promoted take of transplanted hemopoietic precursor cells in the bone marrow of irradiated mice." Bull Exp Biol Med, 2001;131(5):493-5. PMID: 11550064.
- [pubmed] Semina OV, et al. "[The synthetic peptide D-(iEW) (thymodepressin) protects bone marrow CFU-S from ionizing radiation exposure]." Radiats Biol Radioecol, 2000;40(3):315-8. PMID: 10907411.
- [pubmed] Semenets TN, et al. "[Thymodepressin protects murine bone marrow CFU-S from the hyperthermic damage]." Radiats Biol Radioecol, 2005;45(3):324-7. PMID: 16080625.
- [pubmed] Pylev LN, et al. "[Carcinogen activity of the new drug thymodepressin studied in chronic tests on rats and mice]." Eksp Klin Farmakol, 2004;67(4):61-3. PMID: 15500051.
- [review] Deigin VI, et al. "Thymodepressin-Unforeseen Immunosuppressor." Molecules, 2021;26(21). PMID: 34770959.
- [review] Deigin V, et al. "The First Reciprocal Activities of Chiral Peptide Pharmaceuticals: Thymogen and Thymodepressin, as Examples." Int J Mol Sci, 2024;25(9). PMID: 38732260.
- [pubmed] Deigin V, et al. "Novel platform for the preparation of synthetic orally active peptidomimetics with hemoregulating activity. II. Hemosuppressor activity of 2,5-diketopiperazine-based cyclopeptides." Int Immunopharmacol, 2020;81:106185. PMID: 32058926.
- [pubmed] Luo Y, et al. "C/EBPβ Promotes LPS-Induced IL-1β Transcription and Secretion in Alveolar Macrophages via NOD2 Signaling." J Inflamm Res, 2022;15:5247-5263. PMID: 36120185.
- [other] US FDA, Drugs@FDA (openFDA): no application for thymodepressin or orilotimod. Read October 28, 2026.
Sources & Citations
Every study on this page was read from its PubMed record on October 29, 2026, with the full text of the developers' 2021 review. The Russian registrations, uses, regimen, contraindications and side effects come from the product information as summarised on the Vidal.ru drug reference (read October 29, 2026); Russia's state register could not be reached. US and EU status come from Drugs@FDA and the EMA medicines list. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.