Ovagen

A synthetic tripeptide (Glu-Asp-Leu) from the Khavinson bioregulator family, attributed by its developers to the liver and studied within their own research network mainly as a kidney-protective agent in rats and renal cell cultures.

Also referenced as: EDL peptide, Glu-Asp-Leu, Glutamyl-aspartyl-leucine, Peptide EDL, T-35

Also appears in: Longevity

What is Ovagen?

Ovagen is a synthetic tripeptide with the sequence Glu-Asp-Leu (EDL, glutamyl-aspartyl-leucine; molecular weight about 375 Da), one of the short “cytogen” peptides developed at the Saint Petersburg Institute of Bioregulation and Gerontology under Vladimir Khavinson. In the developers’ own review papers it is tabulated as “Ovagen (EDL)” and assigned to the liver, and in their earlier cell-culture work it carries the internal code T-35. Despite the name, it has no connection to the ovary: the name is a coincidence of the developers’ naming scheme. A PubMed search on the word “Ovagen” returns an unrelated ovine follicle-stimulating hormone product used in livestock reproduction; the tripeptide appears under that name only inside the full text of the developers’ own 2022 review.

It appears in the research-peptide market as the liver and gastrointestinal entry in the Khavinson bioregulator line, alongside Livagen (Lys-Glu-Asp-Ala), the older tetrapeptide with the same liver framing. The peer-reviewed literature on the EDL sequence, however, is almost entirely about the kidney.

How it works

The proposed mechanism is the one the Khavinson group applies to all of its short peptides: the tripeptide is thought to enter cells, reach the nucleus, bind specific DNA sequences, and shift the expression of genes tied to cell renewal and senescence. The specific data for EDL are:

• Sequence-specific DNA docking — in molecular docking models of 19 short peptides, EDL and the one-residue-longer bronchial peptide AEDL were predicted to bind the same “ctcc” DNA motif, which the authors offered as the physical basis for gene regulation by ultrashort peptides (Khavinson et al., Bulletin of Experimental Biology and Medicine, 2016, 162(2):288–292)
• Senescence markers in renal cell culture — in young and aged primary renal cell cultures, EDL and the cartilage peptide AED increased proliferation, lowered expression of the aging markers p16, p21, and p53, and raised SIRT6; docking placed both peptides in the minor groove of d(ATATATATAT)2 repeats (Khavinson et al., Advances in Gerontology, 2014, 27(4):651–656, in Russian)
• Matrix remodeling target — in a separate aging kidney-culture study of Ki-67, p53, MMP-14, and IL-8, the kidney polypeptide complex and T-31 (AED) activated cell-renewal markers, while the gelatinase MMP-14 was identified as the target of T-35 (EDL) (Khavinson et al., Bulletin of Experimental Biology and Medicine, 2014, 157(2):261–264)
• Oxidative-stress and energy effects in injured kidney — in rats with gentamicin nephropathy or ischemia/reperfusion injury, EDL prevented the critical fall in antioxidant enzyme activity, suppressed lipid peroxidation, and normalized energy supply to kidney cells, in parallel with preserved diuresis and lower proteinuria (Zamorskii et al., Bulletin of Experimental Biology and Medicine, 2017, 163(3):389–393)

The liver mechanism offered by the developers is restoration of tissue-specific protein synthesis in hepatocytes. The data behind it come from a patent filing, not from a peer-reviewed study, and are described below.

Research status

All published work on EDL comes from one research network (the Saint Petersburg Institute of Bioregulation and Gerontology and collaborators at Bukovinian State Medical University in Chernivtsi). There is no independent replication, no human study in the peer-reviewed literature, and no registered clinical trial on ClinicalTrials.gov under the name Ovagen or the sequence.

Kidney (peer-reviewed, animal and cell culture). Zamorskii et al. (2015) compared a kidney polypeptide complex with the short peptides AED, EDL, and AEDG in rats with cisplatin-induced acute renal failure; EDL and AEDG normalized diuresis, urinary creatinine and its excretion, glomerular filtration rate, and absolute sodium reabsorption and lowered urinary protein, and the authors singled out EDL as having a potent nephroprotective effect (Bulletin of Experimental Biology and Medicine, 159(6):736–739). Zamorskii et al. (2017) extended this to gentamicin nephropathy and ischemia/reperfusion injury, reporting prevention of oliguria and retention azotemia and reduced proteinuria and sodium excretion (Bulletin of Experimental Biology and Medicine, 163(3):389–393). Zamorskii et al. (2018) then gave the same peptides to old rats: EDL increased diuresis 1.2- to 1.4-fold and sodium excretion 1.6-fold, with increased antioxidant enzyme activity and reduced peroxidation in kidney tissue and no morphological sign of nephrotoxicity (Advances in Gerontology, 31(4):498–504, in Russian). The two 2014 cell-culture papers cited above supply the in vitro half of this record.

Liver (patent only). The liver attribution rests on a 2006 Russian priority filing by Khavinson, Grigoriev, Malinin, and Ryzhak, published internationally as WO2007139430 (with Russian and Eurasian family members RU2297239 and EA010156), titled as a peptide substance stimulating liver tissue regeneration. The filing describes rat liver explant growth increased about 28% at 10 ng/mL, roughly doubled mitotic counts 96 hours after two-thirds partial hepatectomy in an 18-rat series, improved liver biochemistry in a six-month carbon tetrachloride model, rodent toxicity studies, and a 34-patient chronic hepatitis series with symptom and enzyme improvements. None of this has appeared as a peer-reviewed paper, the clinical example lacks a stated treatment-arm size and statistical methods, and the international application never entered the European phase and is recorded as ceased. When the developers’ own 2022 review tabulated their peptides, it listed “Ovagen (EDL)” as a nephroprotector with the 2017 kidney paper as the reference and as a hepatoprotector with only this patent as the reference (Khavinson et al., International Journal of Molecular Sciences, 2022, 23(14):7733).

Humans. No human trials. The only human data of any kind are the applicant-reported hepatitis series inside the patent.

Common dosage forms

• Lyophilized powder — vials for reconstitution, commonly labeled in the 20 mg range in vendor listings, sold under the Ovagen name or as EDL
• Oral capsules — the format the Khavinson “cytogen” line uses in its home market, where these products circulate as non-prescription peptide supplements rather than registered medicines; no capsule product sold specifically under the Ovagen name could be identified
• Parenteral acetate salt — the formulation described in the patent filing (acetate ion pair, white amorphous powder); it is not a marketed drug product anywhere

Key considerations

• Regulatory status: Research Market. Ovagen has no FDA approval, no approved product in any jurisdiction on the public record, and no registered clinical development. Its home-market distribution is as a supplement-class bioregulator. The Research Market status reflects the absence of US approval or any development program aimed at approval.
• The liver label and the evidence point in different directions. The liver attribution follows the developers’ naming, patent, and marketing. Readers should know that every peer-reviewed study of the EDL sequence is a kidney study in rats or renal cell culture, and that the sole liver source is a ceased patent application whose data were never published in a journal.
• It is not an ovarian peptide. The name invites the error, and some vendor and forum copy repeats it, but nothing in the developers’ literature ties EDL to ovarian tissue. Literature searches on “Ovagen” return an ovine FSH veterinary product used for superovulation and oocyte maturation in cattle, sheep, goats, and pigs (for example Samartzi et al., Reproduction in Domestic Animals, 2008, 43(2):153–156), which has no relationship to this tripeptide.
• Do not confuse it with Livagen or Bronchogen. Livagen (KEDA) is a different, four-residue molecule with its own patent and literature; Bronchogen (AEDL) differs from EDL by a single N-terminal alanine and is assigned to bronchial epithelium. The three are often conflated in vendor material.
• Safety data are developer-generated and preclinical. Rodent toxicity studies in the patent reported no adverse findings, and the 2018 old-rat study saw no histological nephrotoxicity, but the same study documented a 1.6-fold rise in sodium excretion, a pharmacological effect on renal handling that has never been characterized in humans. There are no human pharmacokinetic, safety, or dose-response data, and the whole evidence base comes from a single research program without outside replication.