EGF

The native 53-amino-acid human growth factor that drives epithelial cell proliferation through the EGF receptor, marketed outside the United States as an intralesional diabetic foot ulcer treatment and used in cosmetics as sh-Oligopeptide-1.

Also referenced as: Epidermal Growth Factor, Human EGF, hEGF, rhEGF, Urogastrone, sh-Oligopeptide-1, Nepidermin, Heberprot-P

Also appears in: Tissue repair

What is EGF?

Epidermal growth factor (EGF) is a native human signaling protein — a single-chain polypeptide of 53 amino acids (about 6.2 kDa) held in its compact fold by three disulfide bridges. Unlike most compounds sold on the research-peptide market, it is not a designed drug candidate but the founding member of an entire growth-factor family: Stanley Cohen isolated it from mouse submaxillary glands while purifying nerve growth factor (Cohen, Journal of Biological Chemistry, 1962;237:1555–1562), and the human protein was later shown to be the same molecule as urogastrone, a gastric-acid-inhibiting factor first noticed in the urine of pregnant women and eventually purified from human urine (Gregory, Nature, 1975;257:325–327). Cohen shared the 1986 Nobel Prize in Physiology or Medicine with Rita Levi-Montalcini for the discovery of growth factors.

EGF reaches the research-peptide market through two doors. The first is cosmetics, where recombinant human EGF is a permitted cosmetic ingredient under the INCI name sh-Oligopeptide-1 and anchors “growth factor” anti-aging serums. The second is wound care, where a Cuban intralesional EGF product (Heberprot-P) built a genuine clinical record in diabetic foot ulcers — a pedigree that skin-repair marketing frequently borrows, even though the settings have little in common.

How it works

• EGF receptor activation. EGF binds the epidermal growth factor receptor (EGFR/ErbB1), a receptor tyrosine kinase; ligand binding drives receptor dimerization and autophosphorylation, activating downstream cascades — RAS–MAPK, PI3K–AKT, and PLCγ among them — that push epithelial cells and fibroblasts toward proliferation, migration, and survival (Carpenter & Cohen, Journal of Biological Chemistry, 1990;265(14):7709–7712; Zeng & Harris, Seminars in Cell & Developmental Biology, 2014;28:2–11).
• Granulation and re-epithelialization in wounds. In chronic wounds, EGF signaling supports granulation tissue formation and wound closure. The intralesional injection route used clinically was designed around wound biology: the surface of a chronic diabetic ulcer is a protease-rich environment that degrades topically applied protein, so injecting the growth factor into the wound bed delivers it to responsive cells in deeper layers (Berlanga et al., MEDICC Review, 2013).
• Gastric acid inhibition. The same molecule was independently discovered as urogastrone because it inhibits gastric acid secretion — the property that led to its purification from urine decades before recombinant production existed (Gregory, Nature, 1975).
• Developmental effects as the original bioassay. EGF was found because submaxillary gland extracts made newborn mice open their eyelids and erupt incisors ahead of schedule; that gross developmental assay guided the original purification (Cohen, Journal of Biological Chemistry, 1962).

Research status

EGF is one of the most-studied proteins in biology — the receptor it activates is a cornerstone of cancer research — but its record as a therapeutic is narrower and almost entirely ex-US.

Diabetic foot ulcers: the core clinical program. Cuban trials of intralesional recombinant human EGF (first as Citoprot-P, then Heberprot-P) progressed from an early trial in amputation-risk ulcers (Fernández-Montequín et al., International Wound Journal, 2007;4(4):333–343) through a 20-patient pilot in which 17 of 20 chronic ulcers closed completely (Fernández-Montequín et al., International Wound Journal, 2009;6(1):67–72) to a multicenter, randomized, placebo-controlled, double-blind study of 149 subjects with Wagner grade 3–4 ulcers. In that trial, granulation tissue covering at least half the ulcer at two weeks — the primary endpoint — was reached by 44/53 patients on 75 µg and 34/48 on 25 µg, versus 19/48 on placebo, with faster complete granulation in both EGF arms; wound closure after follow-up favored the higher dose (40/53 on 75 µg, versus 25/48 on both 25 µg and placebo) (Fernández-Montequín et al., International Wound Journal, 2009;6(6):432–443). A multi-year active post-marketing surveillance program in Cuban clinical practice followed (Yera-Alos et al., BMC Pharmacology and Toxicology, 2013;14:44).

Independent assessments are more reserved. A Cochrane review of 28 randomized trials of any growth factor for diabetic foot ulcers (2,365 participants) concluded that growth factors may increase the likelihood of healing but graded the evidence low quality, with high risk of bias and a possible increase in overall adverse events (Martí-Carvajal et al., Cochrane Database of Systematic Reviews, 2015;(10):CD008548). A later meta-analysis restricted to EGF — six studies, 530 patients — pooled a roughly four-fold odds ratio for complete healing across intralesional and topical routes (Bui et al., International Journal of Environmental Research and Public Health, 2019;16(14):2584), while noting the small trial base.

Regulatory status: approved elsewhere, not in the US. Heberprot-P was approved in Cuba in 2006 and has since been registered in roughly two dozen countries across Latin America, Asia, the Middle East, and parts of Europe. It has never been approved by the FDA. The US embargo kept the product out of American clinics for years; in April 2024 the FDA issued a “Study May Proceed” letter on an IND from Discovery Therapeutics Caribe, clearing the first US phase 3 trial of intralesional rhEGF for refractory diabetic foot ulcers. That is clearance to test, not approval — as of this writing, no EGF product is an FDA-approved drug for any indication. The registered-trial record elsewhere includes a completed demonstrative study of Heberprot-P in Kuwait (ClinicalTrials.gov NCT03239457) and a Brazilian placebo-controlled trial of intralesional rhEGF (NCT02554851). Other recombinant EGF medicines exist only outside the US as well: topical products for ulcers and burns have been marketed in South Korea and India under the INN nepidermin.

Cosmetic use: heavily marketed, weakly supported. The cosmetic literature on sh-Oligopeptide-1 is a different world from the wound-care trials. A critical review of the published cosmetic studies concluded that the preclinical bioactivity of the cosmetic ingredient has not been properly demonstrated, that the supporting clinical studies do not meet medical-trial standards, and that topical recombinant human EGF is not authorized as a medication at any concentration anywhere outside clinical trials (Martínez-Carpio, Cutaneous and Ocular Toxicology, 2023;42(4):190–197). There are no rigorous randomized trials showing that EGF applied to intact skin reverses photoaging or wrinkles.

What does not exist. There are no human trials of injectable EGF for anti-aging, recovery, or general skin quality in healthy people — the injectable clinical record is intralesional injection into open diabetic wounds under medical supervision, and nothing else.

Common dosage forms

• Cosmetic serums and creams listing sh-Oligopeptide-1, typically at parts-per-million concentrations, often blended with other INCI-named growth factors. Some lines use plant-expressed (for example, barley-produced) recombinant human EGF under the same INCI name.
• Lyophilized powder in vials from research suppliers, usually recombinant human EGF expressed in E. coli, in microgram-to-milligram fill sizes (commonly 100 µg to 1 mg) for reconstitution.
• Ex-US pharmaceutical presentations: lyophilized 25 µg and 75 µg vials for intralesional injection (Heberprot-P, administered in clinics where registered), and topical gels or sprays marketed for ulcers and burns in some Asian markets.
• Topical “growth factor complex” blends, where EGF content is not stated separately from other ingredients.

This section describes formats only and is not dosing guidance.

Key considerations

• The ex-US approval does not transfer. Heberprot-P is a prescription biologic, injected into open wounds by clinicians, in the countries where it is registered; it is not FDA approved, and the 2024 US milestone was permission to run a phase 3 trial, not a marketing authorization. Nothing sold as research-market or cosmetic EGF shares that regulatory status, manufacturing oversight, or route of administration.
• EGF is a mitogen, and its receptor is an oncology target. EGFR is overexpressed or mutated in many carcinomas, and an entire class of cancer drugs exists to block the very pathway EGF activates. Clinical trials excluded patients with a history of malignancy, and long-term surveillance has paid specific attention to cancer outcomes. Deliberately applying a proliferation signal over long periods carries a theoretical risk that the wound-care literature manages by short, supervised treatment courses.
• The strong evidence is for injection into wounds, not application to intact skin. A hydrophilic ~6.2 kDa protein does not meaningfully cross an intact stratum corneum, and the critical literature on cosmetic EGF finds the supporting studies methodologically weak (Martínez-Carpio, 2023). Marketing that cites diabetic-wound trial results for an anti-aging serum is citing evidence from a different route, population, and product class.
• Known adverse events in the clinical program. Trials and surveillance of intralesional EGF report injection-site pain and burning, tremors and chills or shivering, and local infection; the Cochrane review flagged a possible increase in overall adverse events across growth-factor trials, on low-quality evidence.
• Naming is a minefield. In older literature the same molecule appears as urogastrone or β-urogastrone, and much foundational work used mouse EGF rather than human. Searches on “EGF” return mostly EGFR-inhibitor oncology literature, which concerns blocking the receptor, not administering the ligand. In cosmetics, sh-Oligopeptide-1 is the recombinant human EGF INCI name, but neighboring INCI names (such as sh-Polypeptide-1) denote entirely different growth factors, and “EGF” on a label can also refer to plant-derived mimetics. Heberprot-P and the earlier Citoprot-P are the same rhEGF program under different names.