Chemical compound
Tapinarof , also known as benvitimod and sold under the brand name Vtama , is a medication used for the treatment of plaque psoriasis .[ 1] The medication is applied to the skin .[ 1] Besides its use in medicine, tapinarof is a naturally occurring compound found in bacterial symbionts of nematodes which has antibiotic properties.[ 2] [ 3]
The medication acts as an aryl hydrocarbon receptor agonist.[ 1] [ 4]
Tapinarof was approved for medical use in the United States in May 2022.[ 1] [ 5] [ 6] [ 7] The US Food and Drug Administration (FDA) considers it to be a first-in-class medication .[ 8] [ 9]
Tapinarof is indicated for the treatment of plaque psoriasis in adults.[ 1]
In case of short term use the most common adverse effects are folliculitis, contact dermatitis, headache, pruritus (itching), and upper respiratory tract infection.[ 10] [ 11]
Mechanism of action [ edit ] 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.[ 12] [ 13] [ 14]
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.[ 10] [ 15]
Tapinarof, also known as benvitimod and sold under the brand name Vtama, is a medication used for the treatment of plaque psoriasis .[ 1] The medication is applied to the skin .[ 1] Besides its use in medicine, tapinarof is a naturally occurring compound found in bacterial symbionts of nematodes which has antibiotic properties.[ 2] [ 3]
The medication acts as an aryl hydrocarbon receptor agonist.[ 1] [ 4] Tapinarof was approved for medical use in the United States in May 2022.[ 1] [ 5] [ 6] [ 7] The US Food and Drug Administration (FDA) considers it to be a first-in-class medication .[ 8]
Society and culture [ edit ] Tapinarof is the international nonproprietary name .[ 16]
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 .[ 2] 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.[ 3]
^ a b c d e f g h i j "Vtama- tapinarof cream" . DailyMed . 23 May 2022. Archived from the original on 3 July 2022. Retrieved 19 June 2022 .
^ a b c Joyce SA, Brachmann AO, Glazer I, Lango L, Schwär G, Clarke DJ, et al. (2008). "Bacterial biosynthesis of a multipotent stilbene". Angewandte Chemie . 47 (10): 1942–1945. CiteSeerX 10.1.1.603.247 . doi :10.1002/anie.200705148 . PMID 18236486 .
^ a b c Hu K, Webster JM (August 2000). "Antibiotic production in relation to bacterial growth and nematode development in Photorhabdus--Heterorhabditis infected Galleria mellonella larvae" . FEMS Microbiology Letters . 189 (2): 219–223. doi :10.1111/j.1574-6968.2000.tb09234.x . PMID 10930742 .
^ a b Bissonnette R, Stein Gold L, Rubenstein DS, Tallman AM, Armstrong A (April 2021). "Tapinarof in the treatment of psoriasis: A review of the unique mechanism of action of a novel therapeutic aryl hydrocarbon receptor-modulating agent" . Journal of the American Academy of Dermatology . 84 (4): 1059–1067. doi :10.1016/j.jaad.2020.10.085 . PMID 33157177 .
^ a b "Vtama: FDA-Approved Drugs" . U.S. Food and Drug Administration (FDA) . Archived from the original on 25 May 2022. Retrieved 24 May 2022 .
^ a b "Vtama (Tapinarof) FDA Approval History" .
^ a b "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" . Dermavant Sciences (Press release). 24 May 2022. Archived from the original on 24 May 2022. Retrieved 24 May 2022 .
^ a b "Advancing Health Through Innovation: New Drug Therapy Approvals 2022" . U.S. Food and Drug Administration (FDA) . 10 January 2023. Retrieved 22 January 2023 . This article incorporates text from this source, which is in the public domain .
^ New Drug Therapy Approvals 2022 (PDF) . U.S. Food and Drug Administration (FDA) (Report). January 2024. Archived from the original on 14 January 2024. Retrieved 14 January 2024 . This article incorporates text from this source, which is in the public domain .
^ a b Nogueira S, Rodrigues MA, Vender R, Torres T (December 2022). "Tapinarof for the treatment of psoriasis" . Dermatologic Therapy . 35 (12): e15931. doi :10.1111/dth.15931 . PMC 10078538 . PMID 36226669 .
^ Lebwohl MG, Stein Gold L, Strober B, Papp KA, Armstrong AW, Bagel J, et al. (December 2021). "Phase 3 Trials of Tapinarof Cream for Plaque Psoriasis" . The New England Journal of Medicine . 385 (24): 2219–2229. doi :10.1056/NEJMoa2103629 . PMID 34879448 . S2CID 245032475 .
^ Bissonnette R, Stein Gold L, Rubenstein DS, Tallman AM, Armstrong A (April 2021). "Tapinarof in the treatment of psoriasis: A review of the unique mechanism of action of a novel therapeutic aryl hydrocarbon receptor-modulating agent" . Journal of the American Academy of Dermatology . 84 (4): 1059–1067. doi :10.1016/j.jaad.2020.10.085 . PMID 33157177 . S2CID 226275222 .
^ Furue M, Hashimoto-Hachiya A, Tsuji G (October 2019). "Aryl Hydrocarbon Receptor in Atopic Dermatitis and Psoriasis" . International Journal of Molecular Sciences . 20 (21): 5424. doi :10.3390/ijms20215424 . PMC 6862295 . PMID 31683543 .
^ Bissonnette R, Vasist LS, Bullman JN, Collingwood T, Chen G, Maeda-Chubachi T (June 2018). "Systemic Pharmacokinetics, Safety, and Preliminary Efficacy of Topical AhR Agonist Tapinarof: Results of a Phase 1 Study". Clinical Pharmacology in Drug Development . 7 (5): 524–531. doi :10.1002/cpdd.439 . PMID 29389078 . S2CID 23107777 .
^ Lebwohl MG, Stein Gold L, Strober B, Papp KA, Armstrong AW, Bagel J, et al. (December 2021). "Phase 3 Trials of Tapinarof Cream for Plaque Psoriasis" . The New England Journal of Medicine . 385 (24): 2219–2229. doi :10.1056/NEJMoa2103629 . PMID 34879448 .
^ World Health Organization (2017). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 78". WHO Drug Information . 31 (3). hdl :10665/330961 .
Dihydroxylated Trihydroxylated Tetrahydroxylated O-methylated
carboxylated other acylations Glycosides
of resveratrol of rhapontigenin
Rhapontigenin 3-O-rutinoside
4'-Methoxy-(E)-resveratrol 3-O-rutinoside
Rhaponticin (Rhapontigenin glucoside)
Oligomeric forms
AhR Tooltip Aryl hydrocarbon receptor
Agonists: Arachidonic acid metabolites (e.g., lipoxin A4 , prostaglandin G2 )
Dietary carotenoids
Flutamide
Halogenated aromatic hydrocarbons (e.g., polychlorinated dibenzodioxins (e.g., TCDD ), dibenzofurans , biphenyls )
ΙΤΕ
Modified low-density lipoproteins
Polycyclic aromatic hydrocarbons (e.g., 3-methylcholanthrene , benzo[a]pyrene , benzanthracenes , benzoflavones (e.g., β-naphthoflavone ))
Tapinarof (benvitimod)
Tetrapyroles (e.g., bilirubin )
Tryptophan derivatives (e.g., indigo dye , indirubin )