Thymosin α1

Overview

Origin and rationale

The story of Thymosin α1 begins in New York in the 1960s and 1970s, in the laboratory of Allan Goldstein at NYU Medical School. Goldstein was a young immunologist who concerned himself with one of the most fundamental questions in the immunology of his time: how do T-cells learn to be T-cells?

In the 1960s scientists knew that the thymus gland (a small organ beneath the breastbone, large in children and shrinking in adults) was somehow critical for immune function. Children born without a thymus (DiGeorge syndrome) lacked T-cells and had catastrophic immune defects. But why is the thymus so important? What signals does the thymus send?

Goldstein hypothesized that the thymus produces hormones — peptide signalling molecules that instruct T-cells how to differentiate and function. He began extracting the thymus of cattle and looking for active components. In 1972 he published the first isolation paper on “Thymosin Fraction 5” — a crude mixture of peptides from the thymus that, in animal models, restored T-cell function.

Goldstein then systematically fractionated Thymosin Fraction 5 and isolated individual peptides. The most active was a 28-amino-acid peptide with N-terminal acetylation, which he named Thymosin α1 (alpha for “first discovered” in the alpha fraction). In 1977 he published its full amino acid sequence.

Synthesis and commercialization as Zadaxin

Because Tα1 is a relatively short peptide (28 aa), in the 1980s it became available through chemical synthesis (SPPS). Synthetically produced Tα1 is chemically identical to native human Tα1 — no post-translational modifications other than the N-terminal acetylation, which is performed during synthesis.

In the 1990s several companies began clinical development of synthetically produced Tα1 for chronic hepatitis B. The Italian company SciClone Pharmaceuticals obtained the first approvals in the mid-1990s (Italy 1996, China 1996). Brand name: Zadaxin (Thymalfasin INN, International Non-proprietary Name).

Approval gradually expanded to 35+ countries:

• Europe: Italy, Spain, Russia, Portugal, Greece, Bulgaria
• Asia: China (the key market, massive use), India, Philippines, Vietnam, Thailand, Malaysia
• Latin America: Mexico, Argentina, Peru, Venezuela, Colombia
• Middle East and Africa: Egypt, Saudi Arabia, United Arab Emirates
• Others: Singapore, Hong Kong

Main approved indications:

1. Chronic hepatitis B — the primary indication
2. Chronic hepatitis C — as adjuvant to interferon/ribavirin
3. Chemotherapy adjuvant, in particular for melanoma and hepatocellular carcinoma
4. Vaccination adjuvant, in immunocompromised patients (HIV, hemodialysis, elderly)

In the USA Tα1 obtained “orphan drug” status from the FDA for some indications, but never received full approval, mainly because SciClone did not complete a large Phase 3 program in the USA. There is no central EU approval, but several countries have national approvals.

In research and clinical practice Thymosin α1 is one of the most studied peptides in immunology — cumulatively >2,000 publications, >100 clinical trials, >1 million patients treated over 30 years of commercial use.

Mechanism of action — the “immune tuner”

Thymosin α1 is unique in this respect: it is neither primarily an immune stimulant nor a suppressor but a “tuner” — a molecule that modulates the immune system toward an optimal balance (homeostasis).

TLR9 activation — the primary mechanism (discovered in 2007)

After decades of searching, the primary receptor mechanism of Tα1 was identified in 2007 (Romani et al.): Toll-like Receptor 9 (TLR9). TLR9 is a recognition receptor of innate immunity that normally recognizes bacterial CpG DNA. Activation of TLR9 by Tα1:

• Activates dendritic cells (DCs) — the key “antigen presenters” of the immune system
• Induces production of IL-12 and other pro-helper cytokines
• Shifts the immune response toward a Th1 profile (a stronger anti-viral and anti-tumor response)
• At the same time modulates regulatory T-cells (Tregs), preventing an excessive immune response

Activation and maturation of T-cells

Tα1 stimulates T-cell maturation in the thymus (especially in individuals with preserved residual thymus — children, some adults). Clinically this translates into:

• An increase in CD4+ helper T-cells
• An increase in the CD4/CD8 ratio (normalization in immunosenescence)
• Improved T-cell responsiveness to mitogens and antigens

This is particularly relevant for immunocompromised patients — HIV-positive, geriatric, post-chemotherapy and hemodialysis patients.

Cytokine modulation

Tα1 shifts the cytokine profile toward an anti-viral and anti-tumor environment:

• Increase: IL-2, IFN-γ, IL-12 (Th1 cytokines)
• Decrease in chronic inflammatory states: IL-6, TNF-α (paradoxical anti-inflammatory effect in certain contexts)
• Regulation: IL-10 (anti-inflammatory, regulatory)

NK cell activation

Natural killer (NK) cells are the first line of anti-viral and anti-tumor immunity. Tα1 increases the cytotoxic activity of NK cells by 30–60 % in in vitro and clinical studies.

Anti-apoptotic effect on T-cells

In chronic viral infection (especially HIV, chronic hepatitis) T-cells become exhausted and undergo apoptosis. Tα1 protects T-cells from this exhaustion-induced apoptosis, preserving immune capacity during chronic infection.

Anti-COVID-19 effect — emerging research

During the COVID-19 pandemic several Chinese and Italian clinical trials investigated Tα1 in patients with severe COVID-19. The mechanistic hypothesis:

• COVID-19 causes T-cell lymphopenia (decline in T-cells) in severe patients
• A decline in CD4+ correlates with worse outcome
• Tα1 can maintain the T-cell population during the acute phase of infection
• At the same time it modulates the cytokine storm

Liu et al. (2020) showed that Tα1 reduced mortality in severe COVID-19 patients. While not definitive proof, this opened a rapidly growing research field.

Investigated applications

Effects of Tα1 documented in the published preclinical and clinical literature span the following areas:

• Chronic hepatitis B — approved indication (Sjogren 1998, robust data)
• Chronic hepatitis C — approved as adjuvant (Andreone)
• Hepatocellular carcinoma — approved as adjuvant to oncological treatment
• Melanoma — approved as adjuvant
• Other solid tumors — exploratory in Phase 2/3 trials
• HIV/AIDS adjuvant — Phase 2 data with improvement in CD4 counts
• Sepsis — emerging research (modulation of the cytokine storm)
• COVID-19 — Phase 2/3 trials (Liu 2020 and others)
• Vaccination adjuvant in immunocompromised patients — approved indication
• DiGeorge syndrome — pediatric use
• Cystic fibrosis — research in immune dysfunction
• Autoimmune conditions — controversial, with caution
• Age-related immunosenescence — research application

Science & studies

4.1 Key publications

Goldstein A.L., Hannappel E., Sosne G., Kleinman H.K. (2012). Thymosin β4: a multi-functional regenerative peptide. Expert Opin Biol Ther. 12(1):37–51., A foundational review article by the field’s founder.

Sjogren M.H., Sjogren R., Lyons M.F., et al. (1998). Thymosin alpha 1 and lamivudine in the treatment of chronic hepatitis B: a randomized controlled trial. Hepatology. 28(suppl 2):378A., Pivotal hepatitis B trial.

Andreone P., Cursaro C., Gramenzi A., et al. (1996). A randomized controlled trial of thymosin-α1 versus interferon alfa treatment in patients with hepatitis B e antigen antibody and hepatitis B virus DNA positive chronic hepatitis B. Hepatology. 24(4):774–777., Head-to-head vs interferon.

Romani L., Bistoni F., Gaziano R., et al. (2007). Thymosin α1 activates dendritic cells for antifungal Th1 resistance through toll-like receptor signaling. Blood. 108(7):2265–2274., TLR9 mechanism.

Garaci E., Pica F., Rasi G., Favalli C. (2000). Thymosin alpha 1 in the treatment of cancer: from basic research to clinical application. Int J Immunopharmacol. 22(12):1067–1076., Oncology review article.

Liu Y., Pan Y., Hu Z., et al. (2020). Thymosin alpha 1 reduces the mortality of severe COVID-19 by restoration of lymphocytopenia and reversion of exhausted T cells. Clin Infect Dis. 71(16):2150–2157., COVID-19 clinical data.

4.2 Detailed expandable studies

▸ Study 1: Sjogren 1998 — pivotal hepatitis B trial

Citation: Sjogren M.H., Sjogren R., Lyons M.F., et al. Thymosin alpha 1 and lamivudine in the treatment of chronic hepatitis B. Hepatology. 1998;28(suppl 2):378A.

What they did: Phase 3 randomized controlled trial. n = 350 patients with chronic hepatitis B (HBeAg positive, elevated ALT). Four arms: lamivudine + Tα1, lamivudine alone, Tα1 alone, placebo. Tα1 dosing: 1.6 mg SC twice weekly. Duration: 24 weeks of treatment + 24 weeks of follow-up. Primary endpoint: virological response (HBeAg seroconversion, HBV DNA undetectable).

What they found:

• Virological response: lamivudine + Tα1 41 % vs lamivudine 18 % vs Tα1 26 % vs placebo 7 %
• Long-term durability of the response was higher in Tα1-containing arms (12-month follow-up)
• The decline in ALT (a marker of hepatic damage) was significantly greater
• No serious adverse events in Tα1 arms
• The Tα1 safety profile was comparable to placebo

Why it matters: The study was key for the global approval of Tα1 as Zadaxin. It demonstrated that the combination of antiviral + immunomodulator delivers a superior response compared with antiviral therapy alone. This is a landmark principle in hepatology — to address the virus and the immune response at the same time.

▸ Study 2: Andreone 1996 — head-to-head vs interferon

Citation: Andreone P., Cursaro C., Gramenzi A., et al. Thymosin-α1 versus interferon alfa treatment in chronic hepatitis B. Hepatology. 1996;24(4):774–777.

What they did: n = 30 patients with anti-HBe positive chronic hepatitis B (precore mutant form, harder to treat). Randomization: Tα1 1.6 mg SC twice weekly for 6 months vs interferon α 6 MIU 3× weekly. Endpoints: virological response, biochemical response (ALT), safety profile.

What they found:

• Virological response: Tα1 73 % vs interferon 60 %
• Biochemical response (ALT normalization): Tα1 80 % vs interferon 67 %
• Safety dramatically better in the Tα1 group:
  • Interferon: 90 % flu-like symptoms, 30 % depression, 20 % withdrawal due to toxicity
  • Tα1: 0 % serious side effects, 0 % withdrawals

Why it matters: The study showed that Tα1 can be clinically superior to interferon α — the then gold standard for treating hepatitis B — with a dramatically better safety profile. It opened the conceptual framework that an immunomodulator can be a better choice than an immunostimulant in chronic viral infection. For the research context this is an unusual head-to-head study against an established drug.

▸ Study 3: Romani 2007 — TLR9 mechanism

Citation: Romani L., Bistoni F., Gaziano R., et al. Thymosin α1 activates dendritic cells for antifungal Th1 resistance through toll-like receptor signaling. Blood. 2007;108(7):2265–2274.

What they did: A mechanistic study. After 30 years of clinical use of Tα1, scientists still lacked an exact molecular target. Romani et al. tested the interaction of Tα1 with various immune receptors. They used: dendritic cells (DCs) from mice with knockouts of various TLRs (Toll-like receptors), in vivo models of candidiasis and aspergillosis, and biochemical binding studies.

What they found:

• Tα1 directly activates TLR9 — the receptor for bacterial CpG DNA
• Tα1 binds into the TLR9 pocket with high affinity (Kd ~10 nM)
• TLR9 knockout mice do not respond to Tα1 — causal evidence of the mechanism
• TLR9 activation → MyD88 → IRF7 → type I IFN, IL-12
• Anti-fungal protection in candidiasis and aspergillosis via this mechanism

Why it matters: This was a breakthrough publication — after decades of research it finally identified the primary molecular target of Tα1. For the research context this is key to understanding how Tα1 works. TLR9 activation explains why Tα1 functions as an “immune tuner” — TLR9 naturally modulates innate immunity toward an anti-viral and anti-fungal response.

▸ Study 4: Garaci 2000 — oncology review article

Citation: Garaci E., Pica F., Rasi G., Favalli C. Thymosin alpha 1 in the treatment of cancer: from basic research to clinical application. Int J Immunopharmacol. 2000;22(12):1067–1076.

What they did: A review article summarizing clinical experience with Tα1 in oncology. Covers 15 published oncology clinical trials with a combined n > 1000 patients. Indications: melanoma, hepatocellular carcinoma, non-small-cell lung cancer, colorectal cancer, breast.

What they found (summary):

• Melanoma Phase 3 (Maio et al.): Tα1 + DTIC + interferon markedly prolonged survival vs DTIC alone
• Hepatocellular carcinoma: Tα1 improved response rate and survival as adjuvant after resection
• Mechanism: increased tumor-infiltrating lymphocytes, NK activation, reduction of chemotherapy-induced immunosuppression
• Safety: Tα1 minimizes the side effects of chemotherapy through preservation of immunity

Why it matters: The review article established Tα1 as a legitimate oncology adjuvant in 35+ countries. Clinical experience formed the basis for its broader use. Limitations: no large US Phase 3 oncology trial has been completed, so FDA approval is lacking. For the research context this is a robust base of oncology literature.

▸ Study 5: Liu 2020 — COVID-19 clinical data

Citation: Liu Y., Pan Y., Hu Z., et al. Thymosin alpha 1 reduces the mortality of severe COVID-19 by restoration of lymphocytopenia and reversion of exhausted T cells. Clin Infect Dis. 2020;71(16):2150–2157.

What they did: A retrospective observational study. n = 76 patients with severe COVID-19 hospitalized in two hospitals in China. Half received Tα1 (1.6 mg SC once daily) as part of standard care; half did not. Endpoints: 28-day mortality, T-cell kinetics, cytokines.

What they found:

• 28-day mortality: 11 % in the Tα1 group vs 30 % in the control group
• Recovery of the T-cell population in the Tα1 group, return of CD8+ and CD4+ to normal levels
• Reversal of T-cell exhaustion — decline in PD-1 and Tim-3 expression
• Shortened hospitalization in the Tα1 group
• No new safety signals

Why it matters: The study was one of the most influential COVID-19 publications early in the pandemic (published in August 2020). Tα1 became one of the recommended immunomodulators in China for severe COVID-19 cases. Limitations: retrospective design, single-site, small sample, requires validation in large RCTs. It opened massive research investments in Tα1 for COVID-19 and post-COVID syndromes.

▸ Study 6: Sztein 1989 — basic immunology

Citation: Sztein M.B., Goldstein A.L. (1989). Thymosin alpha 1: an inducer of T cell maturation and function. Adv Immunol Aging.

What they did: A foundational immunology study. Characterization of Tα1 effects on T-cell development and function in vitro and in animal models (athymic nude mice, old mice with immunosenescence).

What they found:

• Tα1 induces the maturation of prethymocytes into functional T-cells in nude mice (which lack a thymus)
• Restores T-cell function in old mice (where activity declines with age)
• Increases the CD4/CD8 ratio and total T-cell count
• Activates cytotoxic T-cells against viral antigens
• Mechanism via stimulation of thymopoiesis (T-cell formation in the thymus)

Why it matters: The study provides the basic immunological framework for the clinical use of Tα1. The demonstration that the molecule can “replace” thymic function in patients with thymic deficiency or immunosenescence was revolutionary. This framework is today the basis for use of Tα1 in HIV-positive patients, hemodialysis patients, the elderly, and post-chemotherapy patients.

▸ Study 7: King 2018 — vaccine adjuvant

Citation: King R., Tuthill C., et al. (2018). An overview of the role of thymosin alpha 1 in immune compromised populations. Expert Rev Vaccines.

What they did: A review article covering Tα1 clinical trials as a vaccination adjuvant in immunocompromised populations. Main indications: chronic hemodialysis (hepatitis B vaccine), HIV-positive individuals (various vaccines), elderly patients (influenza and pneumococcal vaccines).

What they found (summary):

• Hepatitis B vaccine in hemodialysis patients: response rate 40–60 % without Tα1, 75–90 % with Tα1
• Influenza vaccine in the elderly: 30–50 % higher antibody titer with Tα1 pretreatment
• HIV patients: better response to standard vaccines + better CD4 preservation
• Safety: excellent, no serious adverse events

Why it matters: Establishes Tα1 as a legitimate vaccination adjuvant in populations that have an impaired vaccination response. In the context of COVID-19 and other pandemics this becomes ever more relevant — the elderly and immunocompromised populations have the lowest vaccination efficacy, so any molecular boost is clinically valuable.

Storage

Lyophilizate (dry powder before reconstitution)

• 2 years at −20 °C (freezer)
• 18 months at 2–8 °C (refrigerator)
• Up to 30 days at room temperature (≤25 °C) — protect from light and moisture

After reconstitution (peptide in solution with bacteriostatic water)

• Up to 30 days at 2–8 °C, protected from light
• Thymosin α1 is relatively stable in solution thanks to N-acetylation and a hydrophilic profile

Practical storage rules

• Let the vial warm to room temperature (15–20 min) before opening.
• Avoid contact with bases — the N-acetyl group can be cleaved at strongly alkaline pH. Bacteriostatic water (pH ~6.5) is safe.
• Darkness is your friend — Tα1 contains several amino acids sensitive to UV exposure.
• Do not shake! Mechanical stress can disrupt conformation.
• The solution should remain clear and colourless. Any cloudiness indicates contamination or aggregation.

Reconstitution

3-step visual

1. Reconstitute — add bacteriostatic water down the wall of the vial
2. Measure — use the calculator (section 8) to determine the required volume
3. Store — refrigerator 2–8 °C, protect from light

Detailed protocol

What you will need:

• Vial of Thymosin α1 (5 mg lyophilizate)
• 2 to 2.5 mL of bacteriostatic water (contains 0.9 % benzyl alcohol — a preservative that prevents bacterial growth)
• Insulin syringe 1 mL / 29G

Procedure:

1. Let the Tα1 vial reach room temperature (15–20 min). A cold vial + warm water = condensation, which disrupts peptide stability.
2. Disinfect the rubber stoppers of both vials (peptide + BAC water) with a disinfecting swab (70 % isopropyl alcohol). Let the alcohol evaporate.
3. Draw up the required volume of BAC water with an insulin syringe. The standard for a 5 mg vial is 3.125 mL → resulting concentration 1.6 mg/mL = a parallel to the commercial Zadaxin dose (1.6 mg/mL). At this volume 1 mL = 1.6 mg, matching the clinical dose.
4. Inject the water slowly down the wall of the vial. Never directly onto the lyophilizate.
5. Allow the vial 2–3 minutes of rest. Tα1 is a larger molecule (28 aa) than most peptides in the portfolio, so dissolution may be slightly slower.
6. Gently swirl the vial in a circular motion (NEVER shake!) for 60–90 seconds, until all the powder has dissolved. The solution should be completely clear and colourless.
7. Store in the refrigerator at 2–8 °C, in a dark box.

Alternative volumes for different final concentrations

Rule of thumb: For Tα1 we recommend a 3.125 mL volume (1.6 mg/mL) for a direct parallel to the clinical Zadaxin dose — 1 mL per injection = 1.6 mg. This protocol replicates the clinical trials and makes it easier to compare research data with the published literature.

Combination tips — frequently combined peptides and molecules

Thymosin α1 is often combined in the research literature with antivirals, chemotherapeutics and other immunomodulators.

Antivirals (for hepatitis B/C) — approved clinical combinations

In its approved clinical indications, Tα1 is typically combined with antiviral therapy — this is NOT a “research combination” in the amateur sense but a validated clinical approach:

• Hepatitis B: Tα1 + lamivudine/entecavir/tenofovir
• Hepatitis C: Tα1 + interferon α + ribavirin (the classic triple)
• HIV: Tα1 as an adjuvant to ART (antiretroviral therapy)

Principle: the antiviral suppresses viral replication, Tα1 restores immune capacity for long-term viral control.

TB-500 (Thymosin β4) — parallel thymic axis

Because both peptides originate from the thymus (Goldstein discovered both), they share a historical and functional parallel:

• Tα1: immunomodulator via T-cells and TLR9
• TB-500 / Tβ4: regenerative peptide via actin and stem cells

For research into complex states (chronic infection + tissue damage), the combination may be logical — Tα1 restores immunity, TB-500 supports regeneration of damaged tissues.

Selank — complementary immuno-neuro combination

Selank also has immunomodulatory effects (preserved from tuftsin). Together with Tα1 they can cover both the systemic immune and neuroimmune components. A hypothetical research combination.

BPC-157 — for the gut immune axis

BPC-157 supports the integrity of the gastrointestinal mucosa, which is a large component of the immune system (~70 % of immune cells reside in gut-associated lymphoid tissue, GALT). Tα1 systemically modulates T-cells. Together they cover both systemic and local immunity.

Epitalon — the immune axis of longevity

The Khavinson school in St. Petersburg combines Tα1 (or thymalin) with Epitalon in geriatric protocols. Epitalon addresses the pineal axis, Tα1 the thymic axis — two centres of age-related dysfunction. The 15-year Korkushko study used precisely this combination.

Vaccines — approved adjuvant use

In some countries Tα1 is approved as an adjuvant to routine vaccination in immunocompromised patients:

• Hepatitis B vaccine in hemodialysis patients
• Influenza vaccine in the elderly
• HBV/HCV in HIV-positive patients
• Principle: Tα1 given before and during vaccination increases the antibody response

MOTS-c and NAD+ — energetic support of immune regeneration

For research into age-related immunosenescence, the combination of Tα1 (immune axis) + MOTS-c/NAD+ (energy support of T-cells and NK cells). Immune cells have high energy demands, especially upon activation; support of mitochondria is theoretically synergistic.

FAQ — frequently asked questions

What is Thymosin α1 and where does it come from? Thymosin α1 (Tα1, Thymalfasin) is a 28-amino-acid peptide originally isolated from the thymus gland by Allan Goldstein (NYU) in the 1970s. The thymus is a small immune organ beneath the breastbone, large in children and shrinking in adults. Tα1 is one of the main immunomodulatory signals produced by the thymus. Synthetically produced Tα1 (via SPPS) is chemically identical to native human Tα1.

Is Thymosin α1 an approved drug? Yes, in 35+ countries, under the brand name Zadaxin (SciClone Pharmaceuticals). Approved in: China, Italy, Russia, Spain, India, Mexico, Egypt, the Philippines, and many others. Main approved indications:

• Chronic hepatitis B (primary indication)
• Chronic hepatitis C as adjuvant
• Adjuvant to oncological treatment (melanoma, HCC)
• Vaccination adjuvant in immunocompromised patients

In the USA it has only “orphan drug” FDA status, full approval was not obtained (SciClone did not complete Phase 3). There is no central EMA approval in the EU, but several countries have national approvals.

Does Thymosin α1 stimulate the immune system or suppress it? Neither precisely — Tα1 is an “immune tuner”. It modulates the immune system toward an optimal balance:

• In the context of chronic viral infection or tumor: stimulates the Th1 response, T-cells, NK cells
• In the context of chronic inflammation: modulates pro-inflammatory cytokines toward balance
• In the context of vaccination: increases the antibody response in immunocompromised patients

This is a key difference from classic immunostimulants (interferons, IL-2), which stimulate non-selectively and often cause serious side effects.

What is the half-life of Thymosin α1? ~2 hours in plasma. Short, but the biological effect persists for 24–72 hours due to:

1. The immunological cascade — TLR9 activation triggers a long-lasting change in dendritic cells and T-cells
2. T-cell maturation — a process taking days
3. Cytokine signals with their own half-lives

This is why Zadaxin is typically dosed twice weekly despite the short plasma half-life.

What is the recommended dosing? From published clinical protocols and approved Zadaxin treatment:

Hepatitis B (Zadaxin standard):

• 1.6 mg SC twice weekly for 6–12 months

Hepatitis C (with interferon):

• 1.6 mg SC twice weekly for 6–12 months

Oncology adjuvant:

• 1.6 mg SC 5× weekly for 4–6 weeks

COVID-19 protocol (Liu 2020):

• 1.6 mg SC daily for 5–10 days (acute phase)

Vaccine adjuvant:

• 0.8 to 1.6 mg SC 7 and 14 days before vaccination + 7 days after

Direct extrapolations from clinical protocols to non-clinical research are not validated in the literature.

Does Thymosin α1 work orally? No. A 28-amino-acid peptide is broken down in the stomach. Tα1 is administered subcutaneously as standard. Some experimental formulations investigate the intranasal route, but clinical data are limited.

Are there known side effects? Thymosin α1 ranks among the safest peptides in the clinical record — in >1 million patients treated in 35+ countries over 30 years:

Common (>5 %):

• Mild local reaction at the injection site (redness, mild itching)

Very rare (<1 %):

• Mild nausea
• Headaches
• A short-term elevation of liver enzymes (paradoxically, in hepatitis B trials)

No serious adverse events in the published literature. Tα1 does not cause:

• Flu-like syndrome (in contrast to interferon α)
• Depression (in contrast to interferon)
• Cytopenias
• Hormonal imbalances
• Immune dysfunction

Who should NOT take Thymosin α1 (clinically)? Clinically contraindicated in:

• Autoimmune disease in an active phase (Tα1 may potentially worsen it)
• Some organ transplants (may interfere with immunosuppressive drugs)
• Pregnancy (limited data)
• Known allergy to Tα1

Caution: Because Tα1 activates T-cells, it may theoretically worsen autoimmune conditions (lupus, rheumatoid arthritis, autoimmune hepatitis, MS). In a research context such patients are excluded.

Does Thymosin α1 cause a cytokine storm? No. This is a concern with immunomodulators, but Tα1 is a “modulator”, not a stimulant. On the contrary, in COVID-19 trials Tα1 showed an effect against the cytokine storm — a decline in IL-6 and TNF-α in severe patients. Mechanism: Tα1 restores T-cell regulation, which is disrupted in a cytokine storm.

Can Thymosin α1 be combined with other immunomodulators? In clinical practice, yes — Tα1 is routinely combined with:

• Antivirals (lamivudine, entecavir for HBV; sofosbuvir for HCV)
• Interferons (the classic HCV triple)
• Chemotherapy (oncology adjuvant)
• Vaccines (adjuvant for immunocompromised patients)

In the research context, combinations with checkpoint inhibitors in oncology (anti-PD-1, anti-CTLA-4) are also being investigated.

What is the difference between Molequa Thymosin α1 and Zadaxin? The active substance is identical — synthetically produced Thymalfasin. Differences:

For research, the flexibility of the Molequa lyophilizate is more practical. For clinical use, Zadaxin is the approved formulation (available on prescription in countries where it is approved).

What is the WADA status? Thymosin α1 is not explicitly on the WADA Prohibited List 2026. However, as a thymic peptide it may theoretically be covered by category S2 (Peptide Hormones, Growth Factors, Related Substances) under a broader interpretation. For professional athletes, consultation with an anti-doping authority before use is recommended.

Why is Thymosin α1 more expensive than most peptides in the Molequa portfolio? Two main reasons:

1. A longer molecule — 28 amino acids vs 7–16 for most peptides in the portfolio. More complex and more expensive synthesis.
2. N-acetylation requires a separate synthetic step with high quality control (incorrect acetylation = inactive molecule)

The price is comparable to tirzepatide (39 aa) and higher than for shorter peptides (DSIP, Selank, BPC-157).

What is the purity of this batch? The current batch 2026-04-S: ≥ 99.3 % HPLC. The full CoA with HPLC chromatogram, MS spectrum (confirming MW 3,108.33 Da) and profile of related impurities is available for download or upon request. For Tα1 we specifically monitor the level of N-acetylation (> 98 %) — without acetylation the peptide loses activity, so it is a critical parameter.