Ac-SDKP vs Thymulin

Inhibits hematopoietic stem cell entry into S-phase. Blocks TGF-β1-mediated fibroblast activation, reducing collagen deposition. Promotes angiogenesis via VEGF upregulation. Regulated in vivo by ACE enzyme.

Ac-SDKP (N-acetyl-seryl-aspartyl-lysyl-proline) is an endogenous tetrapeptide generated from the N-terminus of thymosin beta-4 by the enzyme prolyl oligopeptidase, with further regulation by angiotensin-converting enzyme (ACE), and is characterized by roles in hematopoietic progenitor regulation and anti-fibrotic signaling in renal, cardiac, and vascular tissue. Ac-SDKP inhibits collagen synthesis and fibroblast proliferation, reduces TGF-beta-1-mediated fibrotic signaling, and promotes anti-inflammatory macrophage polarization in preclinical models, suggesting a role in tissue homeostasis downstream of the thymosin beta-4 pathway. Preclinical studies in rodent models of renal fibrosis and systemic lupus erythematosus — predominantly from the NIH-funded Rhaleb and Carretero laboratory at Henry Ford Health — have demonstrated that exogenous Ac-SDKP reduces collagen deposition and inflammatory infiltrate; no human clinical trials have been completed or indexed in PubMed. Ac-SDKP has no FDA approval and no approved indication in any jurisdiction; it is studied as a research compound with a plausible anti-fibrotic mechanism and consistent preclinical evidence, but extrapolation of rodent findings to human therapeutic outcomes has not been validated by any clinical investigation.

Zinc-dependent peptide that promotes T-lymphocyte differentiation, enhances natural killer cell activity, and regulates cytokine balance. Requires zinc cofactor for biological activity.

Thymulin (facteur thymique serique; FTS) is an endogenous zinc-dependent nonapeptide (Glu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn) produced exclusively by thymic epithelial cells, identified by Dardenne and Bach in the 1970s as the circulating thymic hormone responsible for promoting T-cell differentiation and maturation in the peripheral immune system. Biological activity of thymulin requires chelation of a zinc ion to form an active complex; the zinc-thymulin complex binds to receptors on immature T-lymphocytes promoting their differentiation, and modulates the neuroendocrine-immune axis through interactions with pituitary hormones, with blood levels of active thymulin declining measurably with age and zinc deficiency. Published reviews from the Dardenne (Institut Pasteur) and Goya groups have established thymulin as a key mediator of thymic-dependent immune senescence, with preclinical data in aged animal models demonstrating partial restoration of immune function following exogenous administration; no human randomized controlled trials have been published. Thymulin has no FDA approval and no approved therapeutic indication in any major jurisdiction; it is a research compound with biological plausibility for immune senescence applications, though the exclusively preclinical evidence base and the zinc-dependency of its active form represent important limitations for any discussion of exogenous supplementation.