Ac-SDKP vs LL-37

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.

Human cathelicidin antimicrobial peptide; disrupts bacterial membranes and modulates innate immune response via TLR signaling

LL-37 is the mature human cathelicidin antimicrobial peptide, a 37-amino-acid cationic peptide generated by proteolytic cleavage of the hCAP18 precursor protein, constitutively expressed in neutrophil granules and inducibly expressed in keratinocytes and epithelial cells of the skin, lung, and gastrointestinal tract as a component of innate antimicrobial defense. LL-37 disrupts bacterial and fungal membranes through electrostatic interaction with anionic lipopolysaccharide and membrane phospholipids, and also modulates inflammatory responses through formyl peptide receptor 2 (FPR2/ALX) activation, promotes wound healing via EGFR transactivation, and contributes to neutrophil extracellular trap formation and antiviral defense. Human studies have documented LL-37 expression in the context of severe soft tissue infections caused by Streptococcus pyogenes, and biochemical characterization of the hCAP18/LL-37 prosequence has identified antimicrobial and protease-inhibitory functions relevant to human skin defense biology. LL-37 is a research compound with no FDA approval for any indication; exogenous synthetic LL-37 administration is investigational with no completed human clinical trials establishing safety or efficacy for wound healing, antimicrobial, or immunomodulatory applications. LL-37 dosage and administration: No human clinical trial has established a dosage protocol for exogenous LL-37. Preclinical and in vitro studies have used LL-37 at concentrations ranging from 1–50 µg/mL in cellular models. Animal models have employed weight-based dosing via subcutaneous or intravenous delivery. Topical formulations for wound healing and antimicrobial applications have been investigated at varying concentrations, with interest in hydrogel delivery systems for sustained local release. LL-37 is rapidly degraded by host proteases in vivo, which limits systemic bioavailability following subcutaneous injection; this degradation susceptibility has driven research into protease-resistant LL-37 analogues and encapsulated formulations. LL-37 is a research compound with no approved human dosing guidelines for any indication.