Ac-SDKP vs Splenin

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.

Spleen-derived tetrapeptide bioregulator; normalizes leukocyte and platelet production; modulates splenic immune cell activity

Splenin is a synthetic tripeptide (Lys-Glu-Asp, KED) classified as a Khavinson-class bioregulator peptide targeted at splenic and immune tissue, investigated for immunomodulatory and cytoprotective properties through proposed gene expression regulatory mechanisms in lymphoid and hematopoietic cell populations. Like other short Khavinson bioregulator peptides, splenin is proposed to modulate gene expression in target immune cells via epigenetic mechanisms, with published research on the class demonstrating that ultrashort peptides can influence differentiation of stem and progenitor cells and regulate gene activity in aging tissues. Research on Khavinson-class ultrashort peptides has characterized neuroepigenetic mechanisms of action in neurodegeneration models and demonstrated peptide regulation of cell differentiation in stem cell preparations, providing the class-level mechanistic context within which splenin is proposed to act on immune tissue. Splenin has no FDA approval or regulatory approval in any major jurisdiction outside Russia; evidence derives from Khavinson-series preclinical and class-level studies with no independent clinical trials published in Western-indexed journals.