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]
Medical uses
Tapinarof is
indicated for the treatment of plaque psoriasis in adults.
[1]
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.
[10]
[11]
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.
[12]
[13]
[14]
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.
[10]
[15]
History
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
Names
Tapinarof is the
international nonproprietary name .
[16]
Natural occurrence
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]
References
^
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
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 )