Prostamax

Identified and synthesised by Vladimir Kh. Khavinson, V.V. Malinin, and E.I. Grigoryev at the St. Petersburg Institute of Bioregulation and Gerontology, Russia, as part of the organ-specific 'cytogen' directed-synthesis programme. The parent polypeptide extract is Prostatilen (from prostate gland tissue); KEDP was isolated as the minimal bioactive sequence after compositional analysis revealed enrichment of lysine, glutamic acid, aspartic acid, and proline at regulatory gene-promoter sites in prostate epithelial cells. Russian Federation Patent RU2177802C1 (published 10 January 2002, inventors Khavinson VKh, Malinin VV, Grigoryev EI; assignee St. Petersburg Institute of Bioregulation and Gerontology) formally claims the tetrapeptide sequence and its use as a prostate-function-regulating pharmacological agent at parenteral doses of 0.01–100 mcg/kg/day. Sold in Russia as a biologically active additive under the Prostamax® brand (TD Peptid Bio / St. Petersburg Institute). Introduced to Western research-chemical markets approximately 2018–2020 as a lyophilised research powder.

Prostamax acts through epigenetic chromatin remodelling without altering the underlying DNA sequence. The proposed cascade is: (1) the peptide penetrates the nucleus and interacts with histone proteins (H1, H2B, H3, H4) and promoter-region dsDNA — a class mechanism demonstrated for short Khavinson-school peptides containing mixed acidic/basic residues including KEDP specifically (PMID 34834147 contextualises the interaction mode); (2) binding shifts the thermal denaturation profile of chromatin — a 2.9°C and 1.0°C temperature shift observed in two denaturation stages of human lymphocyte chromatin (PMID 15612551) — reflecting transition of the 30-nm condensed fibre toward 10-nm open nucleosomal filaments; (3) this deheterochromatinisation increases the frequency of sister-chromatid exchanges to approximately 12.0 per cell vs 5.9 in controls, elevates silver-stained nucleolar organiser region (NOR) counts, and reduces large pericentromeric heterochromatic segments on chromosomes 1 and 9 in elderly-donor lymphocytes (PMID 23221144, PMID 15085253); (4) in prostate epithelial cells the net effect is reactivation of genes governing differentiation, anti-inflammatory signalling, and extracellular-matrix homeostasis — proposed to suppress NF-κB-mediated inflammatory gene programmes; (5) in chronic prostatitis and BPH rat models the tissue-level outcome is reduction of mast-cell and lymphocyte infiltration, decreased vascular congestion, inhibited fibroblast-driven sclerosis, and decreased acinar epithelium area (PMID 17152728, Borovskaya et al. 2013, Borovskaya et al. 2014). Cellular-transport modelling suggests KEDP's mixed charge profile enables uptake via LAT1, LAT2, and PEPT1 transporters, consistent with picomolar-range activity in tissue culture (effective concentration 0.05 ng/ml, PMID 17152728).

Prostate organotypic culture (young and aged rats): stimulated reparative cell activity vs all 20 individual amino acids as controls at 0.05 ng/ml (PMID 17152728); Chronic aseptic prostatitis rat model (15-day course): reduced gland swelling, vascular hyperemia, lymphoid infiltration, and connective-tissue sclerosis; efficacy superior to Serenoa repens extract (Borovskaya et al. 2013, DOI 10.4236/mri.2013.23007); BPH rat model: prostate gland weight and volume decrease, acinar epithelium area reduction by approximately 22.4%; superior to Serenoa repens extract on volume endpoints (Borovskaya et al. 2014, DOI 10.4236/mri.2014.33013); Human lymphocyte chromatin (elderly donors 75–88 yr): sister-chromatid exchange frequency increased from 5.9 ± 0.2 to 12.0 ± 0.28 per cell, elevated NOR counts, reduced heterochromatic segments on chromosomes 1 and 9 (PMID 23221144); Human lymphocyte chromatin denaturation (biophysical): 2.9°C and 1.0°C thermal shifts indicating 30-nm fibre relaxation (PMID 15612551); Ribosomal gene activation and chromatin decondensation in elderly-donor lymphocytes: confirmed alongside Epithalon and Livagen (PMID 15085253); Longevity correlation: KEDP-related sequence motifs present in naked mole-rat proteome (long-lived) but absent in short-lived rodents (PMID 28948547).