Nepidermin
{{Short description|Chemical compound}}
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{{Infobox drug
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| 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
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| tradename = Heberprot-P, Easyef, Genesoft, Kang He Su, Regen-D{{cite web|title=Nepidermin | work = Drugs.com |url=https://www.drugs.com/international/nepidermin.html| archive-url = https://web.archive.org/web/20171213084919/https://www.drugs.com/international/nepidermin.html |access-date=3 June 2017| archive-date = 2017-12-13 }}
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| routes_of_administration = intralesional injection; Topical
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| CAS_number_Ref =
| CAS_number = 62253-63-8
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| PubChem = 16143379
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| ChemSpiderID = 17299876
| UNII = TZK30RF92W
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| C=270 | H=401 | N=73 | O=83 | S=7
| SMILES = CC[C@H](C)[C@@H](C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)N[C@@H](CC4=CNC5=CC=CC=C54)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)O)NC(=O)[C@H](CC6=CC=C(C=C6)O)NC(=O)CNC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC7=CC=C(C=C7)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CC8=CC=C(C=C8)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC9=CN=CN9)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)CNC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CS)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)N)N
| StdInChI_Ref =
| 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_Ref =
| StdInChIKey = GVUGOAYIVIDWIO-UFWWTJHBSA-N
| synonyms = Recombinant human epidermal growth factor; rhEGF; DWP-401
}}
Nepidermin (INN proposed),{{cite journal |title=INN Proposed List 97 |website=www.who.int |url=https://www.who.int/publications/m/item/inn-pl-97 |language=en}} 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.{{cite web|title=Nepidermin|url=http://adisinsight.springer.com/drugs/800016134| work = AdisInsight | publisher = Springer Nature Switzerland AG |access-date=3 June 2017|language=en}}{{cite journal | vauthors = Saygin D, Tabib T, Bittar HE, Valenzi E, Sembrat J, Chan SY, Rojas M, Lafyatis R | title = Transcriptional profiling of lung cell populations in idiopathic pulmonary arterial hypertension | journal = Pulmonary Circulation | volume = 10 | issue = 1 | pages = 403–423 | year = 2016 | pmid = 32166015 | pmc = 7052475 | doi = 10.1007/s40005-016-0268-6 | s2cid = 17779371 }} 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.{{cite journal | vauthors = 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 | title = Heberprot-P: a novel product for treating advanced diabetic foot ulcer | journal = MEDICC Review | volume = 15 | issue = 1 | pages = 11–15 | date = January 2013 | pmid = 23396236 | doi = 10.37757/MR2013V15.N1.4 | doi-access = free }}{{cite journal | vauthors = 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 | title = Intralesional administration of epidermal growth factor-based formulation (Heberprot-P) in chronic diabetic foot ulcer: treatment up to complete wound closure | journal = International Wound Journal | volume = 6 | issue = 1 | pages = 67–72 | date = February 2009 | pmid = 19291119 | pmc = 7951202 | doi = 10.1111/j.1742-481X.2008.00561.x }} As of 2016, Heberprot-P had been marketed in 23 countries,{{Cite web| title = Heberprot-P registered in 23 countries | work = National Network on Cuba| date = 10 June 2016| access-date = 2023-01-16| url = https://nnoc.org/heberprot-p-registered-in-23-countries/}} but remains unavailable in the United States. In 2015, preparations were made to conduct the Phase III trials required for FDA approval,{{Cite web| vauthors = Brenner A | title = U.S. and Cuban companies reach agreement on Heberprot-p| access-date = 2023-01-16| date = 2018-03-22| url = https://www.thecubanhandshake.org/u-s-and-cuban-companies-reach-agreement-on-heberprot-p/ | work = The Cuban Handshake }}{{ClinicalTrialsGov|NCT02554851|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.}} The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz) 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.{{cite web |title=Heberprot-P brochure for professionals |url=https://www.cigb.edu.cu/wp-content/uploads/2021/01/SUELTO-HEBERPROT-PROFESIONALES-ESPANOL-INGLES.pdf |access-date=29 December 2023}} A 1991 paper from Cuba seems to describe its production in more detail.{{cite journal | vauthors = 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 | title = Establecimiento de un cultivo discontinuo para la producción del factor de crecimiento epidérmico humano en levaduras: caracterización del producto | journal = Biotecnologia Aplicada | date = 1991 | volume = 8 | issue = 2 | pages = 166–73 | url = https://www.researchgate.net/publication/288533778 | language = es | trans-title = A batch process for production of human epidermal growth factor in yeast. }} An improved process was described in 2009.{{cite journal | vauthors = Valdés J, Mantilla E, Márquez G, Bonilla RM, Lugo VM, Pérez M, García Y, Narciandi E |title=Improving the expression of human epidermal growth factor in Saccharomyces cerevisiae by manipulating culture conditions |journal=Biotecnologia Aplicada |date=2009 |volume=26 |issue=1 |pages=34–38 |url=http://scielo.sld.cu/pdf/bta/v26n1/bta04109.pdf |issn=0864-4551}}
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.{{cite journal | vauthors = Cho KH, Kim JH, Nam HS, Kang DJ | title = 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 | journal = Geriatrics | volume = 7 | issue = 2 | date = April 2022 | pmid = 35447848 | pmc = 9028627 | doi = 10.3390/geriatrics7020045 | doi-access = free }}
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.{{cite web |title=Epidermal Growth Factor (Human, rDNA derived) WHO International Standard |url=https://nibsc.org/products/brm_product_catalogue/detail_page.aspx?catid=91/530 |website=nibsc.org}}{{cite web |title=Unit Conversion Table |url=https://www.rndsystems.com/resources/technical-information/unit-conversion-table |website=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. However, the WHO does not prescribe a specific way of measuring the potency. rhEGF bioassay remains a field in active development.{{cite journal | vauthors = Qin X, Yao W, Shi X, Liu L, Huang F, Ding Y, Zhou Y, Yu L, Jia C, Li S, Rao C, Wang J | title = Responsive Cells for rhEGF bioassay Obtained through Screening of a CRISPR/Cas9 Library | journal = Scientific Reports | volume = 9 | issue = 1 | pages = 3780 | date = March 2019 | pmid = 30846752 | pmc = 6405917 | doi = 10.1038/s41598-019-40381-4 | doi-access = free | bibcode = 2019NatSR...9.3780Q }}
= Other preparations =
See also
References
{{Reflist}}
{{Preparations for treatment of wounds and ulcers}}
{{Other dermatological preparations}}
{{Growth factor receptor modulators}}