Ac-SDKP vs GLP-2

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.

Binds GLP-2 receptor on intestinal enteroendocrine cells. Promotes enterocyte proliferation and reduces apoptosis, increasing villus height and crypt depth. Strengthens tight junctions and reduces intestinal permeability.

GLP-2 (glucagon-like peptide-2) is a 33-amino-acid endogenous proglucagon-derived peptide secreted by intestinal L-cells in response to nutrient ingestion, functioning as a trophic and protective hormone for the intestinal epithelium with roles in mucosal growth, barrier integrity, and nutrient absorption. GLP-2 signals through a specific receptor (GLP-2R) expressed on intestinal subepithelial myofibroblasts and enteric neurons, promoting enterocyte proliferation while inhibiting apoptosis, reducing intestinal permeability, and modulating gut motility to collectively support intestinal adaptation and absorptive capacity. Clinical evidence for GLP-2 pathway activity is established through teduglutide (Gattex/Revestive), a DPP-IV-resistant GLP-2 analog approved by the FDA in 2012 for short bowel syndrome-associated intestinal failure; Phase 3 trials and long-term follow-up studies demonstrated significant reductions in parenteral nutrition requirements, validating GLP-2 receptor agonism as a viable therapeutic approach. Native GLP-2 itself is not used therapeutically due to a plasma half-life of approximately 7 minutes from rapid DPP-IV degradation; clinical application is exclusively through the stabilized analog teduglutide, which requires a prescription and is indicated specifically for short bowel syndrome — a rare gastrointestinal condition — rather than general wellness or off-label intestinal support.