{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T10:34:47Z","timestamp":1788518087606,"version":"build-2803163510"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T00:00:00Z","timestamp":1674518400000},"content-version":"vor","delay-in-days":39,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UL1 TR003098"],"award-info":[{"award-number":["UL1 TR003098"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR068280"],"award-info":[{"award-number":["AR068280"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR064297"],"award-info":[{"award-number":["AR064297"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Alopecia areata is a chronic hair loss disorder that involves autoimmune disruption of hair follicles by CD8+\u00a0\u00a0T 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 SCD-153, with increased lipophilicity compared to 4-MI (CLogP 1.159\u00a0vs. 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)\u03b3, SCD-153 significantly attenuated poly I:C-induced interleukin (IL)-6, Toll-like receptor 3, IL-1\u03b2, and IFN\u03b2 expression, as well as IFN\u03b3-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.<\/jats:p>","DOI":"10.1093\/pnasnexus\/pgac297","type":"journal-article","created":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T02:34:29Z","timestamp":1671244469000},"source":"Crossref","is-referenced-by-count":15,"title":["Topical SCD-153, a 4-methyl itaconate prodrug, for the treatment of alopecia areata"],"prefix":"10.1093","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3480-2952","authenticated-orcid":false,"given":"Jerry","family":"Tsai","sequence":"first","affiliation":[{"name":"Department of Dermatology, Johns Hopkins University School of Medicine , Baltimore, MD 21205 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0840-829X","authenticated-orcid":false,"given":"Sadakatali","family":"Gori","sequence":"additional","affiliation":[{"name":"Johns Hopkins Drug Discovery, Johns Hopkins University School of 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