Nepidermin Explained

Iupac Name:H-Asn-Ser-Asp-Ser-Glu-Cys-Pro-Leu-Ser-His-Asp-Gly-Tyr-Cys-Leu-His-Asp-Gly-Val-Cys-Met-Tyr-Ile-Glu-Ala-Leu-Asp-Lys-Tyr-Ala-Cys-Asn-Cys-Val-Val-Gly-Tyr-Ile-Gly-Glu-Arg-Cys-Gln-Tyr-Arg-Asp-Leu-Lys-Trp-Trp-Glu-Leu-Arg-OH
Tradename:Heberprot-P, Easyef, Genesoft, Kang He Su, Regen-D
Routes Of Administration:intralesional injection; Topical
Cas Number:62253-63-8
Pubchem:16143379
Chemspiderid:17299876
Unii:TZK30RF92W
C:270
H:401
N:73
O:83
S:7
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Stdinchi:1S/C270H401N73O83S7/c1-24-134(19)217(262(420)293-112-201(355)298-161(69-74-205(359)360)229(387)301-160(45-35-82-286-269(279)280)228(386)333-192(119-428)255(413)307-162(68-73-198(274)352)230(388)316-176(94-141-54-64-150(350)65-55-141)241(399)304-159(44-34-81-285-268(277)278)227(385)325-186(105-212(373)374)248(406)313-169(87-127(5)6)235(393)302-158(43-31-33-80-272)226(384)318-179(97-144-108-289-156-41-29-27-39-153(144)156)243(401)319-178(96-143-107-288-155-40-28-26-38-152(143)155)242(400)305-164(71-76-207(363)364)231(389)312-170(88-128(7)8)236(394)310-167(267(425)426)46-36-83-287-270(281)282)341-250(408)174(92-139-50-60-148(348)61-51-139)300-203(357)113-292-261(419)214(131(13)14)340-264(422)216(133(17)18)339-259(417)195(122-431)335-246(404)182(101-200(276)354)322-257(415)191(118-427)332-220(378)137(22)297-234(392)175(93-140-52-62-149(349)63-53-140)315-225(383)157(42-30-32-79-271)303-247(405)185(104-211(371)372)326-237(395)168(86-126(3)4)311-219(377)136(21)296-224(382)163(70-75-206(361)362)309-265(423)218(135(20)25-2)342-251(409)177(95-142-56-66-151(351)67-57-142)317-233(391)166(78-85-433-23)308-256(414)194(121-430)336-263(421)215(132(15)16)338-204(358)114-291-223(381)184(103-210(369)370)323-244(402)180(98-145-109-283-124-294-145)320-238(396)171(89-129(9)10)314-258(416)193(120-429)334-240(398)173(91-138-48-58-147(347)59-49-138)299-202(356)111-290-222(380)183(102-209(367)368)324-245(403)181(99-146-110-284-125-295-146)321-254(412)190(117-346)330-239(397)172(90-130(11)12)328-260(418)197-47-37-84-343(197)266(424)196(123-432)337-232(390)165(72-77-208(365)366)306-252(410)189(116-345)331-249(407)187(106-213(375)376)327-253(411)188(115-344)329-221(379)154(273)100-199(275)353/h26-29,38-41,48-67,107-110,124-137,154,157-197,214-218,288-289,344-351,427-432H,24-25,30-37,42-47,68-106,111-123,271-273H2,1-23H3,(H2,274,352)(H2,275,353)(H2,276,354)(H,283,294)(H,284,295)(H,290,380)(H,291,381)(H,292,419)(H,293,420)(H,296,382)(H,297,392)(H,298,355)(H,299,356)(H,300,357)(H,301,387)(H,302,393)(H,303,405)(H,304,399)(H,305,400)(H,306,410)(H,307,413)(H,308,414)(H,309,423)(H,310,394)(H,311,377)(H,312,389)(H,313,406)(H,314,416)(H,315,383)(H,316,388)(H,317,391)(H,318,384)(H,319,401)(H,320,396)(H,321,412)(H,322,415)(H,323,402)(H,324,403)(H,325,385)(H,326,395)(H,327,411)(H,328,418)(H,329,379)(H,330,397)(H,331,407)(H,332,378)(H,333,386)(H,334,398)(H,335,404)(H,336,421)(H,337,390)(H,338,358)(H,339,417)(H,340,422)(H,341,408)(H,342,409)(H,359,360)(H,361,362)(H,363,364)(H,365,366)(H,367,368)(H,369,370)(H,371,372)(H,373,374)(H,375,376)(H,425,426)(H4,277,278,285)(H4,279,280,286)(H4,281,282,287)/t134-,135-,136-,137-,154-,157-,158-,159-,160-,161-,162-,163-,164-,165-,166-,167-,168-,169-,170-,171-,172-,173-,174-,175-,176-,177-,178-,179-,180-,181-,182-,183-,184-,185-,186-,187-,188-,189-,190-,191-,192-,193-,194-,195-,196-,197-,214-,215-,216-,217-,218-/m0/s1
Stdinchikey:GVUGOAYIVIDWIO-UFWWTJHBSA-N
Synonyms:Recombinant human epidermal growth factor; rhEGF; DWP-401

Nepidermin (INN proposed),[1] 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. 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.[2] [3] As of 2016, Heberprot-P had been marketed in 23 countries,[4] but remains unavailable in the United States. In 2015, preparations were made to conduct the Phase III trials required for FDA approval,[5] [6] 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.

Production

According to Heber Biotech, nepidermin is made by insering the 53-amino acid human EGF sequence into yeast.[7] A 1991 paper from Cuba seems to describe its production in more detail.[8] An improved process was described in 2009.[9]

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.

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.[10] [11] However, the WHO does not prescribe a specific way of measuring the potency. rhEGF bioassay remains a field in active development.[12]

Easyef

A topical spray formulation has been developed under the brand Easyef by Daewoong Pharmaceutical.[13] [14] [15]

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.[16]

Easyef is made by expression in E. coli. It appears to be less potent than an equivalent concentration of Heberprot in zebrafish.[17]

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.
Easyef Daewoong (Korea) Spray Ulcer, wounds See above. Drugs.com reports marketing in Thailand and Vietnam.
Genesoft (Chinese: 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 (Chinese: 金因肽) Spray Approved in China (Rx, 国药准字 S20010037 - 8). E. coli expression system.[20]
Kang He Su (Chinese: 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 (Chinese: 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. E. coli expression system.[26] Bharat also markets a gel with silver sulfadiazine and chlorhexidine for burns.[27]

See also

Notes and References

  1. INN Proposed List 97 . www.who.int . en.
  2. Berlanga J, Fernández JI, López E, López PA, del Río A, Valenzuela C, Baldomero J, Muzio V, Raíces M, Silva R, Acevedo BE, Herrera L . Heberprot-P: a novel product for treating advanced diabetic foot ulcer . MEDICC Review . 15 . 1 . 11–15 . January 2013 . 23396236 . 10.37757/MR2013V15.N1.4 . free .
  3. Fernández-Montequín JI, Betancourt BY, Leyva-Gonzalez G, Mola EL, Galán-Naranjo K, Ramírez-Navas M, Bermúdez-Rojas S, Rosales F, García-Iglesias E, Berlanga-Acosta J, Silva-Rodriguez R, Garcia-Siverio M, Martinez LH . 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 . 19291119 . 7951202 . 10.1111/j.1742-481X.2008.00561.x .
  4. Web site: Heberprot-P registered in 23 countries . National Network on Cuba. 10 June 2016. 2023-01-16.
  5. Web site: Brenner A . U.S. and Cuban companies reach agreement on Heberprot-p. 2023-01-16. 2018-03-22. The Cuban Handshake .
  6. The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)
  7. Web site: Heberprot-P brochure for professionals . 29 December 2023.
  8. Cinza AM, Quintana M, Lambardero R, Pontón R, Pérez E, Pérez LC, Mella CM, Besada V, Padrón G, Castellanos L, Estrada R, Morales Grillo J . Establecimiento de un cultivo discontinuo para la producción del factor de crecimiento epidérmico humano en levaduras: caracterización del producto . Biotecnologia Aplicada . 1991 . 8 . 2 . 166–73 . es . A batch process for production of human epidermal growth factor in yeast. .
  9. Valdés J, Mantilla E, Márquez G, Bonilla RM, Lugo VM, Pérez M, García Y, Narciandi E . Improving the expression of human epidermal growth factor in Saccharomyces cerevisiae by manipulating culture conditions . Biotecnologia Aplicada . 2009 . 26 . 1 . 34–38 . 0864-4551.
  10. Web site: Epidermal Growth Factor (Human, rDNA derived) WHO International Standard . nibsc.org.
  11. Web site: Unit Conversion Table . R&D Systems.  - 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.
  12. Qin X, Yao W, Shi X, Liu L, Huang F, Ding Y, Zhou Y, Yu L, Jia C, Li S, Rao C, Wang J . Responsive Cells for rhEGF bioassay Obtained through Screening of a CRISPR/Cas9 Library . Scientific Reports . 9 . 1 . 3780 . March 2019 . 30846752 . 6405917 . 10.1038/s41598-019-40381-4 . free . 2019NatSR...9.3780Q .
  13. Web site: Nepidermin . Drugs.com . https://web.archive.org/web/20171213084919/https://www.drugs.com/international/nepidermin.html . 3 June 2017. 2017-12-13 .
  14. Web site: Nepidermin. AdisInsight . Springer Nature Switzerland AG . 3 June 2017. en.
  15. Saygin D, Tabib T, Bittar HE, Valenzi E, Sembrat J, Chan SY, Rojas M, Lafyatis R . Transcriptional profiling of lung cell populations in idiopathic pulmonary arterial hypertension . Pulmonary Circulation . 10 . 1 . 403–423 . 2016 . 32166015 . 7052475 . 10.1007/s40005-016-0268-6 . 17779371 .
  16. Kim JW, Kim MG, Lee HJ, Koh Y, Kwon JH, Kim I, Park S, Kim BK, Oh JM, Kim KI, Yoon SS . 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 . 28045958 . 5207736 . 10.1371/journal.pone.0168854 . free . 2017PLoSO..1268854K .
  17. Cho KH, Kim JH, Nam HS, Kang DJ . 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 . April 2022 . 35447848 . 9028627 . 10.3390/geriatrics7020045 . free .
  18. Web site: GENESOFT(EGF Eyedrop) . www.uni-bioscience.com.
  19. Book: 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 .
  20. Book: 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 .
  21. Web site: 外用重组人表皮生长因子说明书. Package insert: rhEGF for external use . 3healthcare.com . 29 December 2023.
  22. Book: 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 .
  23. Web site: 易孚人表皮生长因子凝胶(酵母)说明书(5万IU(100μg)*10g）- . 亮健好药网手机端. zh. Package insert: Yi Fu hEGF gel (Yeast), 50000IU(100μg)*10g.
  24. Book: 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 .
  25. Web site: Regen-D 150Faster Healing of Foot Ulcers Gel- . Bharat Biotech.  - Manufacturer page with PDFs
  26. Mohan VK . Recombinant human epidermal growth factor (REGEN-D 150): effect on healing of diabetic foot ulcers . Diabetes Research and Clinical Practice . 78 . 3 . 405–411 . December 2007 . 17655964 . 10.1016/j.diabres.2007.06.004 .
  27. Web site: SLVRGEN Wound Healing Epidermal Growth Gel . Bharat Biotech .

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