Topical SCD-153, a 4-methyl itaconate prodrug, for the treatment of alopecia areata

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F23%3A00568134" target="_blank" >RIV/61388963:_____/23:00568134 - isvavai.cz</a>

Result on the web

<a href="https://doi.org/10.1093/pnasnexus/pgac297" target="_blank" >https://doi.org/10.1093/pnasnexus/pgac297</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/pnasnexus/pgac297" target="_blank" >10.1093/pnasnexus/pgac297</a>

Result language

angličtina

Original language name

Topical SCD-153, a 4-methyl itaconate prodrug, for the treatment of alopecia areata

Original language description

Alopecia areata is a chronic hair loss disorder that involves autoimmune disruption of hair follicles by CD8+ T cells. Most patients present with patchy hair loss on the scalp that improves spontaneously or with topical and intralesional steroids, topical minoxidil, or topical immunotherapy. However, recurrence of hair loss is common, and patients with extensive disease may require treatment with oral corticosteroids or oral Janus kinase (JAK) inhibitors, both of which may cause systemic toxicities with long-term use. Itaconate is an endogenous molecule synthesized in macrophages that exerts anti-inflammatory effects. To investigate the use of itaconate derivatives for treating alopecia areata, we designed a prodrug of 4-methyl itaconate (4-MI), termed SCD153, with increased lipophilicity compared to 4-MI (CLogP 1.159 vs. 0.1442) to enhance skin and cell penetration. Topical SCD-153 formed 4-MI upon penetrating the stratum corneum in C57BL/6 mice and showed low systemic absorption. When added to human epidermal keratinocytes stimulated with polyinosinic-polycytidylic acid (poly I:C) or interferon (IFN)γ , SCD-153 significantly attenuated poly I:C-induced interleukin (IL)-6, Toll-like receptor 3, IL-1β, and IFNβ expression, as well as IFNγ -induced IL-6 expression. Topical application of SCD-153 to C57BL/6 mice in the resting (telogen) phase of the hair cycle induced significant hair growth that was statistically superior to vehicle (dimethyl sulfoxide), the less cell-permeable itaconate analogues 4-MI and dimethyl itaconate, and the JAK inhibitor tofacitinib. Our results suggest that SCD-153 is a promising topical candidate for treating alopecia areata.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30107 - Medicinal chemistry

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

PNAS Nexus

ISSN

2752-6542

e-ISSN

2752-6542

Volume of the periodical

2

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

12

Pages from-to

pgac297

UT code for WoS article

001063362300019

EID of the result in the Scopus database

2-s2.0-85178022935