Thymosin Alpha-1 5 mg

Thymosin alpha-1 (Ta1) is a single-chain peptide of 28 amino acids, sequence Ac-SDAAVDTSSEITTKDLKEKKEVVEEAEN, with the alpha-amino group of the N-terminal serine blocked by an acetyl group. The molecular formula of the free peptide is C129H215N33O55 and the average molecular mass is approximately 3108.3 g/mol. It carries CAS registry number 62304-98-7. The synthetic peptide is assigned the international non-proprietary name thymalfasin; PowerfullyPeptides supplies it as a laboratory reagent, not as a medicinal product.

The peptide was first characterised by Goldstein and colleagues in 1977, who isolated it from thymosin fraction 5, a partially purified extract of calf thymus, and determined its 28-residue sequence, describing it as a heat-stable, highly acidic molecule (Goldstein et al., Proc Natl Acad Sci USA, 1977). Later work established that Ta1 corresponds to residues 2 to 29 of a larger intracellular precursor protein, prothymosin alpha, rather than being an independently transcribed gene product; UniProt annotates exactly this peptide within human prothymosin alpha and records its N-terminal serine as N-acetylserine. Material sold today is not extracted from tissue. It is produced by solid-phase peptide synthesis, and a recombinant route in which N-alpha-acetylated Ta1 is released from recombinant prothymosin alpha by legumain cleavage has also been published (Liu B et al., 2013).

The composition is unusual and accounts for the handling behaviour. The sequence contains no aromatic residues, no cysteine, no glycine and no proline, so the peptide has almost no absorbance at 280 nm and cannot form disulfide bridges. It carries nine acidic side chains (three aspartate, six glutamate) against four lysines, and with the N-terminus acetylated the net charge at neutral pH is strongly negative; reported isoelectric points sit near pH 4. Solution-state structure has been examined by NMR: in 40 percent trifluoroethanol / 60 percent water the peptide was reported to adopt an alpha-helix spanning residues 14 to 26, together with two double beta-turns within the N-terminal twelve residues that form a distorted helical region (Elizondo-Riojas et al., 2011).

A widely cited preclinical paper is Romani et al. (Blood, 2004), which reported that Ta1 induced functional maturation and interleukin-12 production by Aspergillus fumigatus-pulsed murine dendritic cells through a p38 MAP kinase / NF-kappaB-dependent pathway, signalling via the MyD88-dependent pathway and involving distinct Toll-like receptors, and that the peptide activated Th1-dependent antifungal immunity in mice. Much of the later mechanistic description of Ta1 as acting on innate immune signalling traces back to this work. No dedicated high-affinity receptor for Ta1 is identified in any of the sources reviewed here.

In clinical research the compound has been studied most heavily in sepsis, and the results moved in one direction over twelve years. The ETASS trial (Wu et al., Crit Care, 2013) was a single-blind, multicentre randomised controlled trial across six tertiary teaching hospitals in China that allocated 361 patients with severe sepsis, 181 to Ta1 and 180 to control. All-cause mortality within 28 days was 26.0 percent (47/181) in the Ta1 arm and 35.0 percent (63/180) in the control arm; the non-stratified comparison gave P = 0.062 and the log-rank test P = 0.049, with a relative risk of 0.74 (95 percent CI 0.54 to 1.02). The authors also reported greater improvement in monocyte HLA-DR expression in the Ta1 arm at day 3 (mean difference 3.9 percent, 95 percent CI 0.2 to 7.6, P = 0.037) and day 7 (mean difference 5.8 percent, 95 percent CI 1.0 to 10.5, P = 0.017).

The same group then ran a larger and more rigorous trial. TESTS (Wu et al., BMJ, 2025) was a multicentre, double-blinded, placebo-controlled phase 3 study; 1,106 adults with sepsis were enrolled and 1,089 were included in the modified intention-to-treat analysis. All-cause 28-day mortality was 23.4 percent (127/542) with Ta1 and 24.1 percent (132/547) with placebo, hazard ratio 0.97 (95 percent CI 0.76 to 1.24, P = 0.82 by log-rank test). Ninety-day mortality was 31.0 percent versus 32.4 percent (HR 0.95, 95 percent CI 0.77 to 1.17, P = 0.61) and ICU mortality was 8.5 percent versus 9.9 percent (P = 0.40). The authors reported that no secondary or safety outcome differed significantly between the groups, and concluded that the trial found no clear evidence that Ta1 decreases 28-day all-cause mortality in adults with sepsis. These are the post-correction figures: a correction to this paper was published (BMJ 2025;389:r1098), and the pre-correction abstract still held in some databases gives a hazard ratio of 0.99 (95 percent CI 0.77 to 1.27, P = 0.93). The conclusion is null either way.

The TESTS prespecified subgroup analysis found heterogeneity of treatment effect by age (P for interaction = 0.01) and by diabetes status (P for interaction = 0.04). The direction was not uniformly favourable, and it is worth stating both halves: participants younger than 60 had higher 28-day mortality in the Ta1 arm (HR 1.67, 95 percent CI 1.04 to 2.67), while participants aged 60 or over (HR 0.81, 95 percent CI 0.61 to 1.09) and participants with diabetes (HR 0.58, 95 percent CI 0.35 to 0.99) did not. The authors treat these as subgroup findings that warrant future investigation rather than as evidence of benefit, and a post-hoc analysis adjusting for organ support before randomisation attenuated the under-60 signal (HR 1.45, 95 percent CI 0.89 to 2.36).

A 2025 systematic review pooling 11 randomised trials and 1,927 septic patients (Gu et al., Front Cell Infect Microbiol) illustrates why the two results differ. The overall pooled estimate favoured Ta1 (OR 0.73, 95 percent CI 0.59 to 0.90, P = 0.003), but when the analysis was restricted to the five higher-quality trials the effect lost significance (OR 0.82, 95 percent CI 0.65 to 1.03, P = 0.09), and the same happened when restricted to multi-centre trials (OR 0.86, 95 percent CI 0.68 to 1.08, P = 0.20). The significant effects sat in the six lower-quality trials (OR 0.41, 95 percent CI 0.24 to 0.68) and in single-centre trials (OR 0.40, 95 percent CI 0.25 to 0.63). Trial sequential analysis indicated the accumulated sample size was still inadequate for a firm conclusion.

Outside sepsis, most of the human literature is observational or consists of small trials. Liu et al. (Clin Infect Dis, 2020) reported a retrospective, non-randomised cohort analysis of hospitalised patients with severe COVID-19 in which Ta1 administration was associated with lower mortality and with changes in circulating CD4+ and CD8+ T-cell counts; because allocation was not controlled, the association cannot be read as an effect. In chronic hepatitis B the evidence base is a set of small and heterogeneous trials; a Cochrane protocol titled 'Thymosin-alpha1 for people with chronic hepatitis B' was registered in 2022 (CD014610, Htet NH and colleagues), and as of this writing the corresponding completed Cochrane review has not been published. Readers should note that the entire clinical record concerns supervised administration in defined patient populations under trial protocols, and says nothing about the behaviour of this material in any other setting.