Vilon

Vilon (L-lysyl-L-glutamic acid; KE dipeptide; CAS 45234-02-4; molecular formula C11H21N3O5; molecular weight 275.30 g/mol) is a synthetic dipeptide bioregulator developed by Vladimir Khavinson and colleagues at the Saint Petersburg Institute of Bioregulation and Gerontology as the minimal pharmacophore unit of the thymic polypeptide extract Thymalin. The compound represents the shortest bioactive peptide characterized in the Khavinson bioregulatory peptide class, consisting of a single lysine residue bonded to a single glutamic acid residue in the alpha-peptide linkage. Despite its minimal chain length, Vilon has demonstrated reproducible immunomodulatory, anti-tumor, geroprotective, and epigenetic activity across more than two decades of experimental investigation conducted primarily in Russian academic institutions and published in the Bulletin of Experimental Biology and Medicine, Biogerontology, Advances in Gerontology, and the International Journal of Molecular Sciences. The principal molecular mechanism, characterized by Lezhava, Khavinson, and Jokhadze in a series of cytogenetic studies from 2003 to 2023, is sequence-specific binding to the tetranucleotide motif TCGA in gene promoter regions, producing deheterochromatinization (decondensation of constitutive and facultative heterochromatin) in aging lymphocytes and thymocytes, with consequent reactivation of ribosomal genes and release of age-repressed transcriptional programs [1, 2, 3]. The immunomodulatory activity, characterized in thymic cell cultures and in the THP-1 monocyte/macrophage cell line, includes upregulation of CD4 and CD5 T-lymphocyte differentiation markers, enhancement of nucleolar organizer region associated protein expression, stimulation of interleukin-2 gene expression in blood lymphocytes, and suppression of lipopolysaccharide-induced tumor necrosis factor alpha and interleukin-6 release from terminally differentiated macrophages [4, 5, 6]. The geroprotective profile, established in female CBA mice receiving subcutaneous Vilon from 6 months of age through the lifespan, includes increased mean lifespan by approximately 24 percent, increased physical activity and endurance, decreased body temperature, and reduced incidence of spontaneous neoplasms including lung adenomas and lymphomas [7, 8]. Antitumor activity was independently confirmed in a chemically induced rat urinary bladder carcinogenesis model, where Vilon reduced tumor incidence from 75.5 percent to 56 percent and inhibited preneoplastic changes in the urothelial mucosa [9]. Clinical application in the Russian Federation, where Vilon has been used in investigational and observational settings for postoperative immune reconstitution, chronic infection management, geriatric immune support, and adjunctive diabetes mellitus management, has produced reports of insulin dose reduction (mean 9 units) in 150 patients with type 1 diabetes and favorable tolerability with no consistent adverse events across multiple cohort studies [10, 11, 12]. Pharmacokinetic data from intestinal tract and liver homogenate studies demonstrate that the KE dipeptide resists hydrolysis in small intestinal preparations and is only marginally degraded in large intestinal and hepatic preparations, supporting oral and parenteral bioavailability [13]. The compound is not approved by the United States Food and Drug Administration or by the European Medicines Agency. It is not registered as a pharmaceutical product outside the Russian Federation. Research-grade Vilon is supplied by multiple peptide synthesis vendors at greater than 98 percent purity by high-performance liquid chromatography. This monograph reviews the chemistry, synthesis, and structural characterization of Vilon; the epigenetic and immunomodulatory mechanisms in molecular detail; the pharmacokinetic data; the preclinical geroprotective and antitumor evidence; the clinical observational evidence; sourcing, reconstitution, and stack-interaction considerations; the adverse-event profile; and a comparative assessment of five thymic and immunomodulatory peptide bioregulators (Thymogen, Thymalin, Thymosin alpha-1, Thymulin, Epithalon) against Vilon on five competency standards.