KLOW Blend 80 mg

KLOW is not a single molecule. The vial contains four separate synthetic peptides co-lyophilised together, with a stated total peptide content of 80 mg: the copper tripeptide GHK-Cu, the pentadecapeptide BPC-157, the thymosin beta-4 fragment sold under the name TB-500, and the tripeptide KPV. Because four distinct chemical entities are present, no single CAS registry number, molecular formula, molecular weight or amino-acid sequence describes the product. Each constituent carries its own identifiers, and a certificate of analysis for a blend of this kind reports each component separately rather than treating the vial as one substance. The proportion of each component is set by the product specification and is reported on the certificate of analysis; it cannot be inferred from the 80 mg total.

GHK-Cu is the tripeptide glycyl-L-histidyl-L-lysine (C14H24N6O4, 340.38 g/mol, CAS 49557-75-7, PubChem CID 73587) coordinated to a copper(II) ion. The free tripeptide occurs naturally in human plasma. The copper complex is registered separately under CAS 89030-95-5 and appears in cosmetic ingredient nomenclature as Copper Tripeptide-1. Published molecular weights for the complex itself vary between sources (401.9 and 403.9 g/mol are both in circulation, and some suppliers describe a two-to-one tripeptide-to-copper stoichiometry rather than one-to-one), so none is quoted here. BPC-157 is a 15-residue peptide, sequence Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val (GEPPPGKPADDAGLV), C62H98N16O22, 1419.56 g/mol, CAS 137525-51-0. It corresponds to a partial sequence of a protein isolated from human gastric juice, which is where the name body protection compound comes from.

TB-500 deserves a plain statement because the naming is routinely muddled in this market. Thymosin beta-4 is a 43-residue protein. The material sold as TB-500 is a short synthetic peptide corresponding to its central actin-binding region, residues 17 to 23, sequence LKKTETQ, usually supplied N-acetylated. Ho and colleagues describe TB-500 in exactly those terms in their 2012 doping-control method paper, which names N-acetylated LKKTETQ as the active ingredient. Two different CAS numbers are in circulation under the single trade name: 885340-08-9 is applied to the short acetylated fragment, and 77591-33-4 to the full-length 43-residue protein, which some suppliers also sell as TB-500. Vendor specification sheets disagree with one another on molecular weight, some quoting figures for the free heptapeptide and others for the acetylated form, and at least one widely copied vendor figure pairs a molecular weight with a formula that does not compute to it. For that reason no CAS or molecular weight for TB-500 is stated here. The fourth component, KPV, is the tripeptide Lys-Pro-Val (C16H30N4O4, 342.43 g/mol, CAS 67727-97-3, PubChem CID 125672), corresponding to residues 11 to 13 of alpha-melanocyte-stimulating hormone, that is, the C-terminal tripeptide of that hormone.

There is no published study of the KLOW combination. A search of the indexed literature returns work on each of the four peptides individually and nothing that examines them administered together. Nothing has therefore been measured about how the four behave as a mixture: whether the copper centre of GHK-Cu affects the stability of the other three in solution, whether any component alters the disposition of another, and whether the combination behaves differently from its parts are all open questions with no data behind them. Vendor pages that describe combined mechanisms for this blend are extrapolating from single-component studies. What follows summarises what has actually been measured for each constituent on its own.

For GHK, the most quantitatively grounded work is Campbell et al. (2012), which approached the peptide computationally rather than starting from it. The authors profiled gene expression in 64 lung-tissue samples (8 regions from each of 8 lungs from smokers with COPD), quantified regional emphysema severity by mean linear intercept from micro-CT, and identified 127 genes whose expression tracked severity. Using the Connectivity Map to search for compounds whose expression signature ran counter to that pattern, GHK was returned as a candidate. In follow-up cell work the authors reported that treating human fibroblasts with GHK recapitulated TGF-beta-induced gene-expression patterns, was accompanied by organisation of the actin cytoskeleton and elevated integrin beta-1 expression, and that adding GHK or TGF-beta restored collagen I contraction and remodelling by fibroblasts derived from COPD lungs compared with fibroblasts from former smokers without COPD. The broader GHK-Cu literature is collected in a 2018 narrative review by Pickart and Margolina. Both authors list their affiliation as R&D Skin Biology, a commercial copper-peptide operation in Bellevue, Washington, and the paper's own statement reads that the authors declare no conflict of interest. That is worth knowing when weighing a single-group review of a compound the same group first characterised.

The BPC-157 work relevant to this blend is preclinical. Chang et al. (2011) cultured tendon explants and tendon fibroblasts from rat Achilles tendon. They reported that BPC 157 significantly accelerated outgrowth of fibroblasts from the explants, that it did not directly affect proliferation of cultured tendon fibroblasts as measured by MTT assay, and that cell survival under hydrogen peroxide stress was significantly increased in treated cells. In transwell filter assays the authors observed a dose-dependent increase in in-vitro migration, with dose-dependent acceleration of cell spreading and induction of F-actin formation on FITC-phalloidin staining. By Western blot, phosphorylation of FAK and paxillin increased dose-dependently while total protein levels of both were unchanged, which led the authors to attribute the effects to activation of the FAK-paxillin pathway. Every measurement in that study is in rat cells and explants; it reports no human data.

For the thymosin beta-4 family, Sosne et al. (2010) reviewed the mapping of the 43-residue protein onto discrete active regions and identified the sequence LKKTETQ, the central actin-binding domain at residues 17 to 23 plus one additional residue, as the segment associated in the literature with angiogenesis, wound healing and cell migration. This is the segment TB-500 corresponds to. The human clinical work on this family, however, used the full-length protein and not the fragment. Guarnera et al. (2010) reported a double-blind, placebo-controlled, dose-escalation phase 2 study in venous stasis ulcers, conducted at eight European sites (five in Italy, three in Poland), which enrolled and randomised 73 patients to topically administered thymosin beta-4 or placebo. The authors reported that the safety profile of all administered doses was acceptable and comparable to placebo, and that a 0.03 percent dose may have the potential to accelerate wound healing, with complete wound healing achieved within three months in about 25 percent of patients, especially among those whose wounds were small to moderate in size or mild to moderate in severity. That trial tested a synthetic copy of the 43-residue peptide applied topically. It is not a study of TB-500 and should not be cited as one.

Of the four, KPV has the most self-contained primary paper. Dalmasso et al. (2008) tested the tripeptide in human intestinal epithelial lines (Caco2-BBE and HT29-Cl.19A) and human Jurkat T cells stimulated with pro-inflammatory cytokines. The authors reported that nanomolar concentrations of KPV inhibited activation of NF-kappaB and MAP kinase signalling and reduced pro-inflammatory cytokine secretion, measured by luciferase reporter, Western blot, real-time RT-PCR and ELISA. Using tritiated KPV and competition against a known PepT1 substrate, they established that uptake occurred through the di/tripeptide transporter PepT1 in both epithelial and immune cells. In mice, KPV added to drinking water reduced the incidence of DSS-induced and TNBS-induced colitis, assessed histologically and by pro-inflammatory cytokine mRNA expression. All of it is cell-culture and rodent work. Taken together, the four components have very different evidence bases: one supported by computational and fibroblast work, one by rodent tendon studies, one whose clinical evidence belongs to a different molecule than the one supplied, and one with a self-contained mechanistic preclinical paper. The blend itself has none.