Thymosin Alpha-1

Thymosin alpha-1 (brand name Zadaxin, generic name thymalfasin) is a synthetic 28-amino-acid peptide best known as an immune-system modulator. It's an approved medicine in 35+ countries outside the US, sold as Zadaxin mainly for chronic hepatitis B, but it has never been approved by the FDA, and as of late 2024 it can't legally be compounded in the US. It's a different molecule from thymosin beta-4 (TB-500) despite the shared name.

Thymosin alpha-1 has been studied mainly as an immune modulator and has a substantial clinical evidence base, including randomized trials in chronic hepatitis B and reports of benefit in severe COVID-19. In severe sepsis the evidence is mixed: a 2013 single-blind trial (ETASS) reported lower 28-day mortality, but a larger 2025 double-blind Phase 3 trial (TESTS, n=1,106) found no significant mortality difference. Its broad "immune optimization" use in otherwise healthy people is not supported by randomized trials and is extrapolated from these clinical-population findings.

Not FDA-approved in the United States. Has received four FDA Orphan Drug Designations but has never advanced to full FDA approval for any indication. Approved as Zadaxin (thymalfasin) in 35+ countries outside the US — primarily for chronic hepatitis B and hepatitis C, with additional approvals in Italy (melanoma adjuvant) and various Latin American, Eastern European, Middle Eastern, and Asia-Pacific markets. Current US compounding status: not legally compoundable under 503A as of December 2024. Brief regulatory timeline: added to FDA's interim 503A bulks list Category 2 (significant safety concerns; restricted from compounding) on September 29, 2023; nominations voluntarily withdrawn by nominators September 20, 2024 with Category 2 placement removed September 27, 2024; FDA evaluated on its own initiative; December 4, 2024 PCAC meeting: committee voted against recommending thymosin alpha-1 (free base) and thymosin alpha-1 acetate for inclusion on the 503A Bulks List. A final Federal Register rule formalizing the post-PCAC determination had still not been published as of 2026-09-03 (re-checked against FDA's 503A bulk-substances page and its PCAC 2026 meeting-materials index). Not listed on the WADA 2026 Prohibited List — direct PDF grep confirms thymosin-β4 and its derivatives are listed under S2.3 (Growth Factors) but thymosin α1 is absent. Not DEA-scheduled.

Thymosin alpha-1 is not FDA-approved in the US and is currently not legally compoundable here, though it is an approved prescription drug in many other countries; it is not on the WADA prohibited list. VialWise is a research and educational reference, not medical advice — consult a licensed professional.

⚠️ For research and educational purposes only. Thymosin alpha-1 is not approved by the FDA in the United States for any indication. It is approved as Zadaxin (thymalfasin) in 35+ countries outside the US for chronic hepatitis B and other indications. Information in this entry is informational, not medical advice. Always confirm dose calculations with the in-app calculator and consult appropriate professional guidance before any protocol decisions.

⚠️ Precision matters at low doses. Thymosin alpha-1 is dosed in milligrams (typical per dose at the Zadaxin label) but at typical reconstitution concentrations ( / 1 mL or / 1 mL =) produces draws in the range on a U-100 syringe. Higher doses or low-concentration reconstitutions push into the overflow range. The dosing-error problem is more analogous to TB-500 (overflow at low concentration) than to the GHRH-analog/microgram-precision problem of CJC-1295 or sermorelin. Always verify draws against the in-app calculator.

⚠️ Thymosin alpha-1 is not thymosin beta-4 (TB-500). Despite the shared "thymosin" prefix, these are completely different molecules from different precursor proteins with different mechanisms. Thymosin alpha-1 (this entry) is a 28-amino-acid immunomodulatory peptide derived from the prothymosin α precursor, primarily affecting innate and adaptive immune function via TLR9 and dendritic cell pathways. Thymosin beta-4 is a 43-amino-acid actin-sequestering protein from a separate family of beta-thymosins that promote tissue repair and angiogenesis. The "thymosin" naming is historical — both were originally isolated from thymosin fraction 5, a bovine-thymus extract characterized in the 1970s before molecular sequencing established that the named fractions came from different protein families. Citations on TB-500 do not apply to thymosin α1, and vice versa. See [tb-500.md](./tb-500.md) for the unrelated thymosin-β4-fragment entry.

⚠️ Distinctive US regulatory category: "FDA-approved-abroad, never-FDA-approved-in-US, currently non-compoundable." Thymosin alpha-1 sits in a regulatory category not previously represented in this library. It is approved as Zadaxin in 35+ countries outside the US (primarily for chronic hepatitis B). It has never received full FDA approval in the US (only four orphan drug designations). It briefly entered FDA Category 2 of the interim 503A bulks list (significant safety concerns; restricted from compounding) on September 29, 2023; the nominations were voluntarily withdrawn in September 2024; the December 4, 2024 PCAC meeting voted against recommending thymosin α1 for inclusion on the 503A Bulks List.[⁷] The practical consequence: thymosin α1 is not legally compoundable through US 503A pharmacies as of late 2024 (no final Federal Register rule has been published, but FDA's position is that compounds not on the bulks list cannot be legally compounded under 503A). Researchers in the US obtaining thymosin α1 for personal use are operating outside the FDA-recognized supply chain. International patients prescribed Zadaxin operate within the regulatory framework of their country.

⚠️ not listed on the WADA 2026 Prohibited List. Direct grep against the canonical WADA 2026 PDF confirms: thymosin-β4 (and its derivatives e.g. TB-500) are listed under Section S2.3 (Growth Factors and Growth Factor Modulators), but thymosin α1 is absent from the document.[⁸] This is consistent with thymosin α1's mechanism — immunomodulation via TLR9 / dendritic cell / T-cell pathways is not within any of the WADA prohibited categories (S0–S9). Researchers competing in WADA-tested sport should still confirm against the current annual edition before competition; the absence of a current listing is not a guarantee of absence in future editions. This is the fourth negative-WADA-listing entry in the library (joining GHK-cu, PT-141, and Liraglutide).

Thymosin alpha-1 (Tα1, thymalfasin) is a 28-amino-acid synthetic peptide corresponding to the N-terminal sequence of prothymosin α, a precursor protein with diverse intracellular functions. Tα1 was originally isolated in the 1970s as the most biologically active fraction of "thymosin fraction 5," a partially purified bovine-thymus extract characterized by Allan Goldstein and colleagues at the National Cancer Institute. Subsequent molecular characterization established its sequence (Ac-Ser-Asp-Ala-Ala-Val-Asp-Thr-Ser-Ser-Glu-Ile-Thr-Thr-Lys-Asp-Leu-Lys-Glu-Lys-Lys-Glu-Val-Val-Glu-Glu-Ala-Glu-Asn) and led to the synthetic version that constitutes the modern pharmaceutical product.[²]

Mechanism. Thymosin α1's mechanism is unusually multifaceted compared to most peptides in this library — it is not a single-receptor agonist but rather a multi-target immunomodulator. The primary mechanism converging from recent (2023–2025) immunology research is modulation of Toll-like receptors, particularly TLR9, on plasmacytoid dendritic cells. Tα1 increases TLR9 expression on pDCs, enhancing detection of viral CpG DNA and triggering activation of interferon regulatory factor 7 (IRF7), with downstream type I interferon (IFN-α) and IFN-γ release.[³] Additional documented mechanisms include: (a) promotion of monocyte-derived dendritic cell maturation with upregulation of HLA class II and costimulatory molecules; (b) Th1 polarization (IFN-γ, IL-2 release); (c) enhancement of NK-cell cytotoxicity; (d) bidirectional modulation of regulatory T-cells; (e) activation of indoleamine 2,3-dioxygenase (IDO) in dendritic cells, which provides a tolerogenic balance preventing immune hyperactivation.[³] This last mechanism — the simultaneous immunostimulatory and tolerogenic activities — is what distinguishes Tα1 from a purely immunostimulatory cytokine and is the basis for its use in both immunodeficient and hyperinflammatory states.

Clinical evidence base. Unusually for a research-community peptide, thymosin α1 has a substantial RCT-grade evidence base. The strongest body of evidence is in chronic hepatitis B, where multiple randomized controlled trials over 25+ years have established efficacy as monotherapy and in combination with interferon-α.[⁴][⁵] The Andreone group at Bologna conducted multiple foundational hepatitis B trials in the 1990s.[⁴] A Japanese RCT (Iino et al. 2005) extended the evidence to East Asian HBV populations.[⁵] Beyond hepatitis B, the severe-sepsis evidence is mixed and not confirmed at phase-3 level: the 2013 ETASS multicenter single-blind RCT in 361 ICU patients reported reduced 28-day mortality (26.0% vs 35.0% in controls),[⁶] but the larger, double-blind, placebo-controlled phase 3 TESTS trial (n=1106, 22 centers) reported no significant difference in 28-day all-cause mortality — 23.4% versus 24.1%, hazard ratio 0.99 (95% CI 0.77–1.27), P=0.93 — with no secondary or safety outcome differing significantly.[¹⁰] During the COVID-19 pandemic, Liu et al. 2020 reported Tα1 reduced mortality in severe COVID-19 patients and restored T-cell numbers in those with severe lymphocytopenia.[⁷] Two recent (2020 and 2024) comprehensive third-party reviews summarize the broader literature.[²][³]

Regulatory status (US — current, May 2026). The US regulatory history for thymosin α1 is the most complex of any compound in this library: - No FDA full approval for any indication. Four FDA Orphan Drug Designations have been granted historically (chronic hepatitis B, chronic hepatitis C, hepatocellular carcinoma, malignant melanoma) but none have advanced to full approval. - September 29, 2023: FDA placed thymosin α1 on the interim 503A bulks list under Category 2 (substances that may pose significant safety risks; restricted from compounding pending PCAC review). - September 20, 2024: Nominations voluntarily withdrawn by nominators (alongside CJC-1295, ipamorelin acetate, AOD-9604, Selank acetate). Category 2 placement removed September 27, 2024. - FDA initiative: Despite the nomination withdrawal, FDA chose to evaluate thymosin α1 (free base) and thymosin α1 acetate on its own initiative. - December 4, 2024 PCAC meeting: The Pharmacy Compounding Advisory Committee voted against recommending thymosin α1 (free base) and thymosin α1 acetate for inclusion on the 503A Bulks List.[⁷] - April 15, 2026: FDA removed 12 peptides from Category 2 of the interim 503A list and scheduled a July 23–24, 2026 PCAC meeting to consider adding seven of them (BPC-157, KPV, MOTS-c, DSIP, Epitalon, Semax, TB-500). Thymosin α1 is not in that batch — it had already had its adverse PCAC review in December 2024. - Status as of 2026-09-03: A final Federal Register rule formalizing the post-PCAC determination has still not been published. FDA's position is that substances not on the 503A Bulks List cannot be legally compounded under 503A. Thymosin α1 is therefore not legally compoundable in the US through 503A pharmacies as of this date.

This regulatory category is distinct from every other category currently represented in this library: - FDA-approved-and-marketed in US (Genotropin, Xyosted, Egrifta, Vyleesi, Saxenda, Victoza, Mounjaro, Ozempic, Wegovy, Zepbound) — full FDA framework - FDA-approved-historically-now-compoundable (Sermorelin) — withdrawn for commercial reasons; FDA Federal Register notice confirmed not for safety/effectiveness; legal via compounding pharmacy - Unapproved research peptide, US-only-research-supply (CJC-1295, BPC-157, TB-500, Ipamorelin, MK-677) — outside FDA approval entirely - DEA-controlled (testosterone) — Schedule III - Federally-distribution-restricted (HGH/somatropin) — 21 USC 333(f) - Generic-available within FDA-approved framework (liraglutide) — first GLP-1 generic

Thymosin α1 establishes a new category: "FDA-approved-abroad in 35+ countries, never-FDA-approved-in-US, currently non-compoundable in US per Dec 2024 PCAC." Researchers obtaining thymosin α1 in the US are doing so outside the FDA-recognized supply chain.

Regulatory status (international). Thymosin α1 is approved as Zadaxin (thymalfasin) in 35+ countries outside the US — primarily for chronic hepatitis B and hepatitis C. Italy approves it as a melanoma adjuvant. Approvals span Latin America, Eastern Europe, the Middle East, and the Asia-Pacific region. International patients prescribed Zadaxin operate within the regulatory framework of their country and are not affected by the US 503A determination.

Common research interests. Despite the US regulatory complexity, thymosin α1 is one of the most-researched immunomodulatory peptides in the research community, primarily for: - Immune support during or after immunosuppressive treatment (chemotherapy, transplant, etc.) — extrapolated from the published immune-reconstitution literature - Vaccine adjuvant — published evidence supports enhanced antibody response to hepatitis B and influenza vaccines in elderly and immunocompromised populations - Adjunct in chronic viral infections (chronic hepatitis B, hepatitis C, less commonly chronic Epstein-Barr or other viral states) — published evidence base - General "immune optimization" / immunosenescence — the dominant research-community use case in non-clinical contexts; this use is not supported by RCT-grade evidence in healthy individuals and is explicitly extrapolated from clinical-population data - Adjunct to cancer immunotherapy — emerging research interest as a "priming" agent before checkpoint inhibitor therapy. A 2026 review of Tα1 combined with immune checkpoint inhibitors describes synergistic remodeling of the tumor immune microenvironment with manageable safety, and concludes that large trials are warranted — i.e. this remains an investigational thread, not established practice.[¹²]

Commonly reported

• Injection site reactions — most common reported adverse event; local pain, redness, mild swelling. Typically mild and transient.
• Mild fatigue during the first 1–2 weeks of dosing — uncommon
• Transient "flu-like" symptoms — uncommon; described as low-grade malaise in early cycles
• Headache — uncommon
• Rash — rare; described in case reports rather than RCTs
• Active autoimmune disease — immune activation may theoretically exacerbate autoimmune flares; case-report-level evidence only
• Active solid-organ-transplant recipients — immunostimulation runs counter to required immunosuppression; clinical decision required
• Active hyperinflammatory state in critically ill patients — published trials in sepsis (ETASS) and severe COVID-19 (Liu 2020) suggest net benefit, but the "is this patient too inflamed for immunostimulation?" question is a clinical judgment in critical-care contexts

Hypersensitivity to thymosin α1, mannitol (a common excipient in lyophilized formulations), or other product components

Pregnancy and lactation — Category C in the Zadaxin labeling framework; insufficient human data; default to contraindicated in research-community use

Pediatric use — not established in research-community contexts; pediatric clinical use exists in some international markets under specialist supervision

Active autoimmune disease — see Side Effects

Active immunosuppressive therapy (transplant immunosuppression, intentional cytotoxic immunosuppression) — see Common Stacks & Combinations

Concurrent biologic immunomodulators (TNF inhibitors, IL-6 inhibitors, JAK inhibitors) — no published interaction data; theoretical concern about immunomodulator-on-immunomodulator effects

Regulatory note (US): thymosin α1 is not FDA-approved in the United States and not legally compoundable through US 503A pharmacies as of December 2024. Researchers obtaining thymosin α1 in the US are operating outside the FDA-recognized supply chain. International patients prescribed Zadaxin operate within their country's regulatory framework.

Regulatory note (sport): thymosin α1 is not listed on the WADA 2026 Prohibited List — confirmed by direct grep against the canonical 2026 PDF.[⁸] This is the fourth negative-WADA-listing entry in the library. Re-verify against the current annual edition before competition; absence of a listing in 2026 is not a guarantee of absence in 2027 or beyond.

Not DEA-scheduled.

Peptide

A short chain of amino acids, the building blocks of proteins. Many compounds in this library are peptides.

Subcutaneous

An injection into the fatty layer just under the skin, rather than into a muscle or vein.

Half-life

Roughly how long the body takes to clear half of a dose. A long half-life is why some compounds can be taken only once a week.

Compounding pharmacy

a pharmacy that prepares a medication to order under a prescription.

1. SciClone Pharmaceuticals. Zadaxin (thymalfasin) prescribing information / Indonesian regulatory dossier. Indonesian National Agency of Drug and Food Control assessment available at registrasiobat.pom.go.id/files/assesment-reports/01751602483.pdf. Source for: Zadaxin commercial label dose ( or/m² SC twice weekly for chronic hepatitis B); pharmacokinetic parameters (~2 hour plasma half-life; peak serum at ~2 hours post-SC; volume of distribution 5–8 L; 31–60% urinary excretion; no accumulation across multiple doses); single-use vial commercial formulation. Note: SciClone Pharmaceuticals is the originator developer of Zadaxin; international labeling varies by country. The Indonesian assessment is one of the more accessible English-language regulatory dossiers.
2. Dominari A, Hathaway D 3rd, Pandav K, Matos W, Biswas S, Reddy G, Thevuthasan S, Khan MA, Mathew A, Makkar SS, Zaidi M, Fahem MMM, Beas R, Castaneda V, Paul T, Halpern J, Baralt D. (2020). Thymosin alpha 1: A comprehensive review of the literature. World Journal of Virology, 9(5):67–78.(PMID 33362999)
3. Dinetz E, Lee E. (2024). Comprehensive Review of the Safety and Efficacy of Thymosin Alpha 1 in Human Clinical Trials. Alternative Therapies in Health and Medicine, 30(1):6–12.(PMID 38308608)
4. Andreone P, Cursaro C, Gramenzi A, Zavaglia C, Rezakovic I, Altomare E, Severini R, Franzone JS, Albano O, Ideo G, Bernardi M, Gasbarrini G. (1996). A randomized controlled trial of thymosin-alpha1 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.(PMID 8855175)
5. Iino S, Toyota J, Kumada H, Kiyosawa K, Kakumu S, Sata M, Suzuki H, Martins EB. (2005). The efficacy and safety of thymosin alpha-1 in Japanese patients with chronic hepatitis B; results from a randomized clinical trial. Journal of Viral Hepatitis, 12(3):300–306.(PMID 15850471)
6. Wu J, Zhou L, Liu J, Ma G, Kou Q, He Z, Chen J, Ou-Yang B, Chen M, Li Y, Wu X, Gu B, Chen L, Zou Z, Qiang X, Chen Y, Lin A, Zhang G, Guan X. (2013). The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial. Critical Care, 17(1):R8.(PMID 23327199 · NCT00711620)
7. Liu Y, Pan Y, Hu Z, Wu M, Wang C, Feng Z, Mao C, Tan Y, Liu Y, Chen L, Li M, Wang G, Yuan Z, Diao B, Wu Y, Chen Y. (2020). Thymosin Alpha 1 Reduces the Mortality of Severe Coronavirus Disease 2019 by Restoration of Lymphocytopenia and Reversion of Exhausted T Cells. Clinical Infectious Diseases, 71(16):2150–2157.(PMID 32442287)
8. US Food and Drug Administration. December 4, 2024 Pharmacy Compounding Advisory Committee meeting materials and outcomes. PCAC meeting transcript ("A Matter of Record" official transcription): fda.gov/media/185641/download. FDA briefing materials: fda.gov/media/183945/download (meeting materials) and fda.gov/media/184043/download (briefing document). The PCAC voted against recommending thymosin α1 (free base) and thymosin α1 acetate for inclusion on the 503A Bulks List at the December 4, 2024 meeting, alongside parallel "no" votes for CJC-1295 and AOD-9604 at the same session. The voting procedure used: a single combined vote on both thymosin α1 (free base) and thymosin α1 acetate, with the provision that any committee member could trigger separate per-substance votes by voting "no" on the combined-vote procedure. The post-PCAC final Federal Register rule has not yet been published as of May 2026. This is the citation for the entry's "currently non-compoundable in US per Dec 2024 PCAC" framing. Background context: thymosin α1 was placed on FDA's interim 503A bulks list under Category 2 (significant safety risks; restricted from compounding) on September 29, 2023; nominations voluntarily withdrawn September 20, 2024; Category 2 placement removed September 27, 2024; FDA elected to evaluate on its own initiative; PCAC December 2024 vote rejected 503A bulks list inclusion.
9. World Anti-Doping Agency. The 2026 Prohibited List, International Standard (effective 1 January 2026). Canonical PDF: wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf (linked from the WADA landing page; local archival copy in `docs/legal/wada-2026-prohibited-list.pdf`). Thymosin α1 is not listed anywhere in the canonical 2026 PDF. Direct grep against the locally-archived PDF returns only thymosin-β4-related listings (Section S2.3, Growth Factors and Growth Factor Modulators: "Thymosin-ß4 and its derivatives e.g. TB-500") — thymosin α1 is absent from the prohibited list. This is consistent with thymosin α1's mechanism (immunomodulation via TLR9 / dendritic cells / T cells) falling outside any of the WADA prohibited categories.
10. Wu J, Pei F,... Guan X. (2025). The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial. BMJ, 388:e082583 (published 2025-01-15).(PMID 39814420 · NCT02867267)
11. Li ZH, Wu LL,... Lin BL. (2026). Thymosin α1 improves the outcomes of patients with hepatitis B virus-related acute-on-chronic liver failure by restoring immune balance. Immunopharmacology and Immunotoxicology, 48(2):341–353.(PMID 41887933 · NCT03082885)
12. Guo H, Li R. (2026). Thymosin α1 combined with immune checkpoint inhibitors: synergistic remodeling of the tumor immune microenvironment. Frontiers in Immunology, 17:1762151.(PMID 42292432)

• LL-37 — same mechanism class
• VIP — same mechanism class
• Crystagen — shared research area
• Thymalin — shared research area
• Vilon — shared research area