Biology:Nepidermin

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Short description: Chemical compound
Nepidermin
Clinical data
Trade namesHeberprot-P, Easyef, Genesoft, Kang He Su, Regen-D[1]
Other namesRecombinant human epidermal growth factor; rhEGF; DWP-401
Routes of
administration		intralesional injection; Topical
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC270H401N73O83S7
Molar mass6222.03 g·mol−1
3D model (JSmol)

Nepidermin (INN proposed),[2] also known as recombinant human epidermal growth factor (rhEGF), is a recombinant form of human epidermal growth factor (EGF) and a cicatrizant (a drug that promotes wound healing through formation of scar tissue). As a recombinant form of EGF, nepidermin is an agonist of the epidermal growth factor receptor (EGFR), and is the first EGFR agonist to be marketed.[3][4] It was developed by Cuban Center for Genetic Engineering and Biotechnology (CIBG), and has been marketed by Heber Biotech as an intralesional injection for diabetic foot ulcer under the trade name Heberprot-P since 2006.[5][6] As of 2016, Heberprot-P had been marketed in 23 countries,[7] but remains unavailable in the United States. In 2015, preparations were made to conduct the Phase III trials required for FDA approval,[8][9] however as of 2023 developments in U.S.-Cuba relations have stymied importation of the drug from Cuba.

Various forms of rhEGF are marketed for the treatment of diabetic foot ulcers, wounds, and alopecia (hair loss) in Vietnam, the Philippines , Thailand, and China .[1][3][4]

Production

According to Heber Biotech, nepidermin is made by insering the 53-amino acid human EGF sequence into yeast.[10] A 1991 paper from Cuba seems to describe its production in more detail.[11] An improved process was described in 2009.[12]

Other rhEGFs

Several other products containing recombinant human EGF have been marketed. The potencies of these products can differ by the expression system used, despite all intending to match the structure of human EGF.[13]

Instead of measuring by mass, the international unit system from the World Health Organization provides a way to describe the potency-adjusted amount of rhEGF.[14][15] However, the WHO does not prescribe a specific way of measuring the potency. rhEGF bioassay remains a field in active development.[16]

Easyef

A topical spray formulation has been developed under the brand Easyef by Daewoong Pharmaceutical.[1][3][4]

A Daewoong-funded Phase II study evaluating nepidermin oral spray for chemotherapy-induced oral mucositis did not reduce incidence or duration of moderate or severe oral mucositis, however per-protocol analysis suggested nepidermin oral spray might reduce pain associated with oral mucositis.[17]

Easyef is made by expression in E. coli. It appears to be less potent than an equivalent concentration of Heberprot in zebrafish.[13]

Other preparations

List of rhEGF preparations
Brand name Manufacturer Form Indication Description
Heberprot-P Heber (Cuba) Lyophilized powder Ulcer See above. Drugs.com reports marketing in Vietnam and Georgia.[1]
Easyef Daewoong (Korea) Spray Ulcer, wounds See above. Drugs.com reports marketing in Thailand and Vietnam.[1]
Genesoft (金因舒)[18] Uni-Bio (Hong Kong); Licensed to GeneTech (China) Eye drop Corneal damage (?) Approved in China (Rx, 国药准字 S20040006). Yeast expression system.[19]
GeneTime (金因肽) Spray Approved in China (Rx, 国药准字 S20010037–8). E. coli expression system.[20]
Kang He Su (康合素)[21] Haohai (China) Lyophilized powder second-degree burns, wounds, ulcers Approved in China (Rx, 国药准字 S20010094–6, S20010099). To be used as a part of wound dressing, soaked in gauze. E. coli expression system.[22]
Yi Fu (易孚)[23] Gel second-degree burns, wounds, ulcers Approved in China (Rx). Yeast expression system.[24]
Regen-D[25] Bharat Biotech (India) Gel Diabetic foot ulcer Approved in India and Thailand.[1] E. coli expression system.[26] Bharat also markets a gel with silver sulfadiazine and chlorhexidine for burns.[27]

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 "Nepidermin". Drugs.com. https://www.drugs.com/international/nepidermin.html. 
  2. ↑ (in en) INN Proposed List 97. https://www.who.int/publications/m/item/inn-pl-97. 
  3. ↑ 3.0 3.1 3.2 "Nepidermin" (in en). AdisInsight. Springer Nature Switzerland AG. http://adisinsight.springer.com/drugs/800016134. 
  4. ↑ 4.0 4.1 4.2 "Transcriptional profiling of lung cell populations in idiopathic pulmonary arterial hypertension". Pulmonary Circulation 10 (1): 403–423. 2016. doi:10.1007/s40005-016-0268-6. PMID 32166015. 
  5. ↑ "Heberprot-P: a novel product for treating advanced diabetic foot ulcer". MEDICC Review 15 (1): 11–15. January 2013. doi:10.37757/MR2013V15.N1.4. PMID 23396236. 
  6. ↑ "Intralesional administration of epidermal growth factor-based formulation (Heberprot-P) in chronic diabetic foot ulcer: treatment up to complete wound closure". International Wound Journal 6 (1): 67–72. February 2009. doi:10.1111/j.1742-481X.2008.00561.x. PMID 19291119. 
  7. ↑ "Heberprot-P registered in 23 countries". National Network on Cuba. 10 June 2016. https://nnoc.org/heberprot-p-registered-in-23-countries/. 
  8. ↑ "U.S. and Cuban companies reach agreement on Heberprot-p". The Cuban Handshake. 2018-03-22. https://www.thecubanhandshake.org/u-s-and-cuban-companies-reach-agreement-on-heberprot-p/. 
  9. ↑ Clinical trial number NCT02554851 for "Efficacy and Safety Evaluation of the Intralesional Recombinant Human Epidermal Growth Factor (rhEGF) in Subjects With Diabetic Foot Ulcer. Multicenter, Randomized, Double-blind, Placebo-controlled Study." at ClinicalTrials.gov The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)
  10. ↑ "Heberprot-P brochure for professionals". https://www.cigb.edu.cu/wp-content/uploads/2021/01/SUELTO-HEBERPROT-PROFESIONALES-ESPANOL-INGLES.pdf. 
  11. ↑ Cinza, A. M.; Quintana, M.; Lambardero, R.; Pontón, R.; Pérez, E.; Pérez, L. C.; Mella, C. M.; Besada, V. et al. (1991). "Establecimiento de un cultivo discontinuo para la producción del factor de crecimiento epidérmico humano en levaduras: caracterización del producto" (in es). Biotecnologia Aplicada 8 (2): 166–73. https://www.researchgate.net/publication/288533778. 
  12. ↑ Valdés, Jorge; Mantilla, Ernesto; Márquez, Gabriel; Bonilla, Regla M.; Lugo, Victoria M.; Pérez, Mariela; García, Yanara; Narciandi, Emilio (2009). "Improving the expression of human epidermal growth factor in Saccharomyces cerevisiae by manipulating culture conditions". Biotecnologia Aplicada 26 (1): 34–38. ISSN 0864-4551. http://scielo.sld.cu/pdf/bta/v26n1/bta04109.pdf. 
  13. ↑ 13.0 13.1 Cho, KH; Kim, JH; Nam, HS; Kang, DJ (6 April 2022). "Efficacy Comparison Study of Human Epidermal Growth Factor (EGF) between Heberprot-P and Easyef in Adult Zebrafish and Embryo under Presence or Absence Combination of Diabetic Condition and Hyperlipidemia to Mimic Elderly Patients.". Geriatrics 7 (2). doi:10.3390/geriatrics7020045. PMID 35447848. 
  14. ↑ "Epidermal Growth Factor (Human, rDNA derived) WHO International Standard". https://nibsc.org/products/brm_product_catalogue/detail_page.aspx?catid=91/530. 
  15. ↑ "Unit Conversion Table". https://www.rndsystems.com/resources/technical-information/unit-conversion-table.  – Provides information on "unit" conversion of a number of hormones. According to the table, this supplier's rhEGF is 1.4 times as potent as the reference 91/530 at the same mass.
  16. ↑ Qin, X; Yao, W; Shi, X; Liu, L; Huang, F; Ding, Y; Zhou, Y; Yu, L et al. (7 March 2019). "Responsive Cells for rhEGF bioassay Obtained through Screening of a CRISPR/Cas9 Library.". Scientific Reports 9 (1): 3780. doi:10.1038/s41598-019-40381-4. PMID 30846752. Bibcode: 2019NatSR...9.3780Q. 
  17. ↑ "Topical Recombinant Human Epidermal Growth Factor for Oral Mucositis Induced by Intensive Chemotherapy with Hematopoietic Stem Cell Transplantation: Final Analysis of a Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial". PLOS ONE 12 (1): e0168854. 2017-01-03. doi:10.1371/journal.pone.0168854. PMID 28045958. Bibcode: 2017PLoSO..1268854K. 
  18. ↑ "GENESOFT(EGF Eyedrop)". http://www.uni-bioscience.com/Home/ourwork/genesoft/language/en. 
  19. ↑ "人表皮生长因子滴眼液 [Human Epidermal Growth Factor Eye Drops"]. 中国药典 [Pharmacopoeia of the People's Republic of China]. 3. https://db.ouryao.com/yd2020/view.php?id=fc8de65057. 
  20. ↑ "人表皮生长因子外用溶液（I）[Human Epidermal Growth Factor Derivative for External Use，Liquid (I)"]. 中国药典 [Pharmacopoeia of the People's Republic of China]. 3. https://db.ouryao.com/yd2020/view.php?id=fc1d886bd5. 
  21. ↑ "外用重组人表皮生长因子说明书". https://www.3healthcare.com/files_s/kanghesu1.pdf. 
  22. ↑ "外用人表皮生长因子 [Human Epidermal Growth Factor for External Use"]. 中国药典 [Pharmacopoeia of the People's Republic of China]. 3. https://db.ouryao.com/yd2020/view.php?id=fd4dfde5d3. 
  23. ↑ "易孚人表皮生长因子凝胶(酵母)说明书(5万IU(100μg)*10g）-" (in zh). https://m.360lj.com/product/instruction/748033.html. 
  24. ↑ "人表皮生长因子凝胶 [Human Epidermal Growth Factor Gel"]. 中国药典 [Pharmacopoeia of the People's Republic of China]. 3. https://db.ouryao.com/yd2020/view.php?id=fc5d3f7614. 
  25. ↑ "Regen-D 150|Faster Healing of Foot Ulcers Gel-". https://www.bharatbiotech.com/regend150.html.  – Manufacturer page with PDFs
  26. ↑ Mohan, VK (December 2007). "Recombinant human epidermal growth factor (REGEN-D 150): effect on healing of diabetic foot ulcers.". Diabetes Research and Clinical Practice 78 (3): 405–11. doi:10.1016/j.diabres.2007.06.004. PMID 17655964. 
  27. ↑ "SLVRGEN| Wound Healing Epidermal Growth Gel". https://www.bharatbiotech.com/slvrgen.html. 



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