Tapinarof

{{Short description|Chemical compound}} {{Use American English|date=May 2022}} {{Use dmy dates|date=May 2022}} {{cs1 config |name-list-style=vanc |display-authors=6}} {{Infobox drug | image = Benvitimod.svg | image_class = skin-invert-image | width = | alt = | caption =

| legal_AU =  | legal_AU_comment = | legal_BR =  | legal_BR_comment = | legal_CA = Rx-only | legal_CA_comment = <ref>{{cite web | title=Nduvra Product information | website=Health Canada | date=4 April 2025 | url=https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=93392 | access-date=17 April 2025}}</ref><ref>{{cite web | title=Register of Innovative Drugs | website=Health Canada | url=https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/register-innovative-drugs.html | access-date=9 May 2025}}</ref> | legal_DE =  | legal_DE_comment = | legal_NZ =  | legal_NZ_comment = | legal_UK =  | legal_UK_comment = | legal_US = Rx-only | legal_US_comment = <ref name="Vtama FDA label">{{cite web | title=Vtama- tapinarof cream | website=DailyMed | date=23 May 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9309d20f-8cd4-4c96-93fa-7f730e83c7ab | access-date=19 June 2022 | archive-date=3 July 2022 | archive-url=https://web.archive.org/web/20220703054146/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9309d20f-8cd4-4c96-93fa-7f730e83c7ab | url-status=live }}</ref> | legal_EU = | legal_EU_comment = | legal_UN =  | legal_UN_comment = | legal_status =

| CAS_number = 79338-84-4 | CAS_supplemental = | PubChem = 6439522 | IUPHAR_ligand = | DrugBank = DB06083 | ChemSpiderID = 4943924 | UNII = 84HW7D0V04 | UNII_Ref = {{fdacite|correct|FDA}} | KEGG = D11365 | ChEBI = | ChEMBL = 259571 | NIAID_ChemDB = | PDB_ligand = | synonyms = Benvitimod; GSK-2894512; (''E'')-3,5-Dihydroxy-4-isopropyl-''trans''-stilbene; 3,5-Dihydroxy-4-isopropylstilbene

| IUPAC_name = 5-[(''E'')-2-Phenylethen-1-yl]-2-(propan-2-yl)benzene-1,3-diol | C=17 | H=18 | O=2 | SMILES = CC(C)c1c(cc(cc1O)/C=C/c2ccccc2)O | StdInChI = 1S/C17H18O2/c1-12(2)17-15(18)10-14(11-16(17)19)9-8-13-6-4-3-5-7-13/h3-12,18-19H,1-2H3/b9-8+ | StdInChI_comment = | StdInChIKey = ZISJNXNHJRQYJO-CMDGGOBGSA-N }}

'''Tapinarof''', also known as '''benvitimod''' and sold under the brand name '''Vtama''' among others, is a medication used for the treatment of plaque psoriasis.<ref name="Vtama FDA label" /> The medication is applied to the skin.<ref name="Vtama FDA label" /> Besides its use in medicine, tapinarof is a naturally occurring compound found in bacterial symbionts of nematodes which has antibiotic properties.<ref name="pmid18236486" /><ref name="pmid10930742" />

The medication acts as an aryl hydrocarbon receptor agonist.<ref name="Vtama FDA label" /><ref name="Tapinarof in the treatment of psori">{{cite journal | vauthors = Bissonnette R, Stein Gold L, Rubenstein DS, Tallman AM, Armstrong A | title = Tapinarof in the treatment of psoriasis: A review of the unique mechanism of action of a novel therapeutic aryl hydrocarbon receptor-modulating agent | journal = Journal of the American Academy of Dermatology | volume = 84 | issue = 4 | pages = 1059–1067 | date = April 2021 | pmid = 33157177 | doi = 10.1016/j.jaad.2020.10.085 | title-link = doi | doi-access = free }}</ref>

Tapinarof was approved for medical use in the United States in May 2022.<ref name="Vtama FDA label" /><ref name="Vtama: FDA-Approved Drugs">{{cite web | title=Vtama: FDA-Approved Drugs | website=U.S. Food and Drug Administration (FDA) | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=215272 | access-date=24 May 2022 | archive-date=25 May 2022 | archive-url=https://web.archive.org/web/20220525070132/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=215272 }}</ref><ref name="drugs.com">{{cite web | url=https://www.drugs.com/history/vtama.html | title=Vtama (Tapinarof) FDA Approval History }}</ref><ref name="dermavant.com">{{cite press release | title=FDA Approves Dermavant's Vtama (tapinarof) cream, 1% for the Treatment of Plaque Psoriasis in Adults: First Topical Novel Chemical Entity Launched for Psoriasis in the U.S. in 25 Years | website=Dermavant Sciences | date=24 May 2022 | url=https://www.dermavant.com/u-s-fda-approves-our-novel-topical-treatment-for-adults-with-plaque-psoriasis/ | access-date=24 May 2022 | archive-date=24 May 2022 | archive-url=https://web.archive.org/web/20220524211841/https://www.dermavant.com/u-s-fda-approves-our-novel-topical-treatment-for-adults-with-plaque-psoriasis/ | url-status=live }}</ref> The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.<ref name="New Drug Therapy Approvals 2022">{{cite web | title=Advancing Health Through Innovation: New Drug Therapy Approvals 2022 | website=U.S. Food and Drug Administration (FDA) | date=10 January 2023 | url=https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/new-drug-therapy-approvals-2022 | access-date=22 January 2023}}{{dead link|date=May 2025|bot=medic}}{{cbignore|bot=medic}} {{PD-notice}}</ref><ref>{{cite report | title=New Drug Therapy Approvals 2022 | website=U.S. Food and Drug Administration (FDA) | date=January 2024 | url=https://www.fda.gov/media/164429/download | format=PDF | access-date=14 January 2024 | archive-url=https://web.archive.org/web/20240114065648/https://www.fda.gov/media/164429/download | archive-date=14 January 2024 | url-status=live }} {{PD-notice}}</ref>

== Medical uses == Tapinarof is indicated for the treatment of plaque psoriasis in adults.<ref name="Vtama FDA label" />

== Side effects == In case of short term use the most common adverse effects are folliculitis, contact dermatitis, headache, pruritus (itching), and upper respiratory tract infection.<ref name=":1">{{cite journal | vauthors = Nogueira S, Rodrigues MA, Vender R, Torres T | title = Tapinarof for the treatment of psoriasis | journal = Dermatologic Therapy | volume = 35 | issue = 12 | article-number = e15931 | date = December 2022 | pmid = 36226669 | pmc = 10078538 | doi = 10.1111/dth.15931 }}</ref><ref>{{cite journal | vauthors = Lebwohl MG, Stein Gold L, Strober B, Papp KA, Armstrong AW, Bagel J, Kircik L, Ehst B, Hong HC, Soung J, Fromowitz J, Guenthner S, Piscitelli SC, Rubenstein DS, Brown PM, Tallman AM, Bissonnette R | title = Phase 3 Trials of Tapinarof Cream for Plaque Psoriasis | journal = The New England Journal of Medicine | volume = 385 | issue = 24 | pages = 2219–2229 | date = December 2021 | pmid = 34879448 | doi = 10.1056/NEJMoa2103629 | s2cid = 245032475 | doi-access = free }}</ref>

== Pharmacology ==

=== Mechanism of action === Tapinarof binds directly to topical aryl hydrocarbon receptor (AhR), suppressing inflammatory cytokines, modulating skin barrier protein expression, reducing oxidative stress, and regulating gene expression in immune cells.<ref>{{cite journal | vauthors = Bissonnette R, Stein Gold L, Rubenstein DS, Tallman AM, Armstrong A | title = Tapinarof in the treatment of psoriasis: A review of the unique mechanism of action of a novel therapeutic aryl hydrocarbon receptor-modulating agent | journal = Journal of the American Academy of Dermatology | volume = 84 | issue = 4 | pages = 1059–1067 | date = April 2021 | pmid = 33157177 | doi = 10.1016/j.jaad.2020.10.085 | s2cid = 226275222 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Furue M, Hashimoto-Hachiya A, Tsuji G | title = Aryl Hydrocarbon Receptor in Atopic Dermatitis and Psoriasis | journal = International Journal of Molecular Sciences | volume = 20 | issue = 21 | page = 5424 | date = October 2019 | pmid = 31683543 | pmc = 6862295 | doi = 10.3390/ijms20215424 | doi-access = free }}</ref><ref name=":0">{{cite journal | vauthors = Bissonnette R, Vasist LS, Bullman JN, Collingwood T, Chen G, Maeda-Chubachi T | title = Systemic Pharmacokinetics, Safety, and Preliminary Efficacy of Topical AhR Agonist Tapinarof: Results of a Phase 1 Study | journal = Clinical Pharmacology in Drug Development | volume = 7 | issue = 5 | pages = 524–531 | date = June 2018 | pmid = 29389078 | doi = 10.1002/cpdd.439 | s2cid = 23107777 }}</ref>

=== Efficacy === Tapinarof 1% cream once daily was superior to vehicle control in reducing the severity of plaque psoriasis over a period of 12 weeks and having a favorable safety profile in the treatment of psoriatic patients.<ref name=":1" /><ref>{{cite journal | vauthors = Lebwohl MG, Stein Gold L, Strober B, Papp KA, Armstrong AW, Bagel J, Kircik L, Ehst B, Hong HC, Soung J, Fromowitz J, Guenthner S, Piscitelli SC, Rubenstein DS, Brown PM, Tallman AM, Bissonnette R | title = Phase 3 Trials of Tapinarof Cream for Plaque Psoriasis | journal = The New England Journal of Medicine | volume = 385 | issue = 24 | pages = 2219–2229 | date = December 2021 | pmid = 34879448 | doi = 10.1056/NEJMoa2103629 | doi-access = free }}</ref>

== History == Tapinarof, also known as benvitimod and sold under the brand name Vtama, is a medication used for the treatment of plaque psoriasis.<ref name="Vtama FDA label" /> The medication is applied to the skin.<ref name="Vtama FDA label" /> Besides its use in medicine, tapinarof is a naturally occurring compound found in bacterial symbionts of nematodes which has antibiotic properties.<ref name="pmid18236486" /><ref name="pmid10930742" />

The medication acts as an aryl hydrocarbon receptor agonist.<ref name="Vtama FDA label" /><ref name="Tapinarof in the treatment of psori"/> Tapinarof was approved for medical use in the United States in May 2022.<ref name="Vtama FDA label" /><ref name="Vtama: FDA-Approved Drugs"/><ref name="drugs.com"/><ref name="dermavant.com"/> The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.<ref name="New Drug Therapy Approvals 2022" />

==Society and culture==

===Names=== Tapinarof is the international nonproprietary name.<ref>{{cite journal | year = 2017 | title = International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 78 | journal = WHO Drug Information | volume = 31 | issue = 3 | page = | hdl = 10665/330961 | hdl-access = free }}</ref>

==Natural occurrence== [[File:Entomopathogenic nematode (Heterorhabditis bacteriophora ) Poinar, 1975.jpg|thumb|right|Entomopathogenic nematodes emerging from a wax moth cadaver.]]

Tapinarof, also known as benvitimod, is a bacterial stilbenoid produced in ''Photorhabdus'' bacterial symbionts of ''Heterorhabditis'' nematodes. It is a product of an alternative ketosynthase-directed stilbenoid biosynthesis pathway. It is derived from the condensation of two β-ketoacyl thioesters.<ref name="pmid18236486">{{cite journal | vauthors = Joyce SA, Brachmann AO, Glazer I, Lango L, Schwär G, Clarke DJ, Bode HB | title = Bacterial biosynthesis of a multipotent stilbene | journal = Angewandte Chemie | volume = 47 | issue = 10 | pages = 1942–1945 | year = 2008 | pmid = 18236486 | doi = 10.1002/anie.200705148 | citeseerx = 10.1.1.603.247 }}</ref> It is produced by the ''Photorhabdus luminescens'' bacterial symbiont species of the entomopathogenic nematode, ''Heterorhabditis megidis''. Experiments with infected larvae of ''Galleria mellonella'', the wax moth, support the hypothesis that the compound has antibiotic properties that help minimize competition from other microorganisms and prevents the putrefaction of the nematode-infected insect cadaver.<ref name="pmid10930742">{{cite journal | vauthors = Hu K, Webster JM | title = Antibiotic production in relation to bacterial growth and nematode development in Photorhabdus--Heterorhabditis infected Galleria mellonella larvae | journal = FEMS Microbiology Letters | volume = 189 | issue = 2 | pages = 219–223 | date = August 2000 | pmid = 10930742 | doi = 10.1111/j.1574-6968.2000.tb09234.x | doi-access = free }}</ref>

== References == {{Reflist}}

Category:Psoriasis Category:Stilbenoids