Dipeptide Limited Human
Thymagen
Synthetic EW dipeptide (Glu-Trp) isolated from thymalin — the smallest active unit of thymic bioregulation, registered as Thymogen in Russia since 1990 for immunodeficiency and respiratory infections.
In Plain English:
Thymagen (also spelled Thymogen; INN: Oglufanide) is a synthetic two-amino-acid peptide composed of glutamic acid and tryptophan (Glu-Trp; single-letter code EW). It was isolated from the natural calf thymic polypeptide extract Thymalin using reverse-phase HPLC by Vladimir Khavinson and colleagues at the Military Medical Academy, St. Petersburg, in the 1980s. The dipeptide is one of three biologically active fractions of Thymalin — alongside KE (Vilon) and EDP (Crystagen) — and represents its primary immunomodulatory unit. Unlike Thymalin, Thymagen is fully synthetic and chemically defined, giving it consistent batch-to-batch identity. It binds to AACG sequences in double-stranded DNA and to histone proteins, shifting gene expression in thymic and immune cells. The downstream result is bidirectional immune normalisation: weakened immunity is strengthened and excessive responses are dampened, making it a true immunomodulator rather than a simple stimulant. In a 12-month rat study, subcutaneous Thymagen (5 µg × 5 days/week) extended maximum lifespan by 10.4% and reduced hematopoietic malignancies by 3.4-fold. It has been registered as a pharmaceutical drug in Russia in three formulations — intramuscular injection, nasal spray, and topical cream — and has been in clinical use for over 35 years with no documented serious adverse events. Outside Russia and the former Soviet Union it has no EMA, FDA, or MHRA approval and is sold as a research peptide.
Research Maturity
Limited Human (~120+ PubMed records on thymogen/Glu-Trp; no Phase III RCTs; nearly all from the Khavinson group+ Studies)
Focus
Adjunct Support in Immunodeficiency
Healthy Aging
Immunity
Origin
Isolated from bovine thymic polypeptide extract (Thymalin) by reverse-phase HPLC at the Military Medical Academy, St. Petersburg, USSR, by V.Kh. Khavinson and V.G. Morozov in the 1980s. Subsequently synthesised chemically. Registered as a pharmaceutical drug (Thymogen®) in the USSR/Russian Federation in 1990 in three formulations: IM injection (100 µg/ml), nasal spray (25 µg/dose), and cream (0.05%). INN name: Oglufanide. Also known as EW dipeptide, glutamyl-tryptophan, Timogen, NSC 334073.
Mechanism
Thymagen binds to AACG motifs in double-stranded DNA and to histone proteins H1 and H3, modulating chromatin accessibility and transcription of immune-regulatory genes. Key downstream effects: (1) Enhanced differentiation of T-lymphocyte precursors into mature CD3+, CD4+, and CD8+ cells — normalising T-helper/cytotoxic ratios in secondary immunodeficiency; (2) Bidirectional cAMP/cGMP regulation via phosphodiesterase modulation — restoring intracellular nucleotide balance in activated immune cells; (3) Upregulation of immunoglobulin synthesis (IgA, IgG, IgM, IgE); (4) Activation of neutrophilic chemotaxis and phagocytosis; (5) Enhancement of NK cell and macrophage activity; (6) Reduction of pro-inflammatory cytokines TNF-α and IL-6; (7) Polyclonal reduction of overactivated immune clones — attenuating autoimmune flares during infection. Radioactive-labelling distribution studies show highest post-injection accumulation in thymus, liver, plasma, adrenal glands, kidneys, and lymph nodes.
Outcome
Maximum lifespan (rodent model); tumour incidence (total, malignant, haematopoietic); T-lymphocyte subset counts CD3/CD4/CD8; T-helper:cytotoxic ratio; NK cell activity; immunoglobulin levels (IgA/IgG/IgM); neutrophil phagocytic index; acute respiratory infection incidence and severity; candidiasis severity score; immunogram normalisation rate in immunodeficiency.
