Home Newsletters Dermal Cell News Discovery of a Novel RORγ Antagonist with Skin-Restricted Exposure for Topical Treatment...

Discovery of a Novel RORγ Antagonist with Skin-Restricted Exposure for Topical Treatment of Mild to Moderate Psoriasis

0
To alleviate the potential safety concerns, identifying compounds with skin-restricted exposure amenable for topical use was of great interest.
[Scientific Reports]
7753456 {7753456:V578WDEP} apa 50 1 161790 https://www.stemcellsciencenews.com/wp-content/plugins/zotpress/
%7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3A%22zotpress-10152814d13a6b28c8c6108adc8259ae%22%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22V578WDEP%22%2C%22library%22%3A%7B%22id%22%3A7753456%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Liu%20et%20al.%22%2C%22parsedDate%22%3A%222021-04-28%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ELiu%2C%20S.%2C%20Liu%2C%20D.%2C%20Shen%2C%20R.%2C%20Li%2C%20D.%2C%20Hu%2C%20Q.%2C%20Yan%2C%20Y.%2C%20Sun%2C%20J.%2C%20Zhang%2C%20F.%2C%20Wan%2C%20H.%2C%20Dong%2C%20P.%2C%20Feng%2C%20J.%2C%20Zhang%2C%20R.%2C%20Li%2C%20J.%2C%20Zhang%2C%20L.%2C%20%26amp%3B%20Tao%2C%20W.%20%282021%29.%20Discovery%20of%20a%20novel%20ROR%26%23x3B3%3B%20antagonist%20with%20skin-restricted%20exposure%20for%20topical%20treatment%20of%20mild%20to%20moderate%20psoriasis.%20%3Ci%3EScientific%20Reports%3C%5C%2Fi%3E%2C%20%3Ci%3E11%3C%5C%2Fi%3E%281%29%2C%209132.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41598-021-88492-1%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41598-021-88492-1%3C%5C%2Fa%3E%20%3Ca%20title%3D%27Cite%20in%20RIS%20Format%27%20class%3D%27zp-CiteRIS%27%20href%3D%27https%3A%5C%2F%5C%2Fwww.stemcellsciencenews.com%5C%2Fwp-content%5C%2Fplugins%5C%2Fzotpress%5C%2Flib%5C%2Frequest%5C%2Frequest.cite.php%3Fapi_user_id%3D7753456%26amp%3Bitem_key%3DV578WDEP%27%3ECite%3C%5C%2Fa%3E%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Discovery%20of%20a%20novel%20ROR%5Cu03b3%20antagonist%20with%20skin-restricted%20exposure%20for%20topical%20treatment%20of%20mild%20to%20moderate%20psoriasis%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Suxing%22%2C%22lastName%22%3A%22Liu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Dong%22%2C%22lastName%22%3A%22Liu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ru%22%2C%22lastName%22%3A%22Shen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Di%22%2C%22lastName%22%3A%22Li%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Qiyue%22%2C%22lastName%22%3A%22Hu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yinfa%22%2C%22lastName%22%3A%22Yan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jiakang%22%2C%22lastName%22%3A%22Sun%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Fengqi%22%2C%22lastName%22%3A%22Zhang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Hong%22%2C%22lastName%22%3A%22Wan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ping%22%2C%22lastName%22%3A%22Dong%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jun%22%2C%22lastName%22%3A%22Feng%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Rumin%22%2C%22lastName%22%3A%22Zhang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jing%22%2C%22lastName%22%3A%22Li%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Lianshan%22%2C%22lastName%22%3A%22Zhang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Weikang%22%2C%22lastName%22%3A%22Tao%22%7D%5D%2C%22abstractNote%22%3A%22Clinical%20success%20of%20IL-17%5C%2FIL-23%20pathway%20biologics%20for%20the%20treatment%20of%20moderate%20to%20severe%20psoriasis%20suggests%20that%20targeting%20ROR%5Cu03b3t%2C%20a%20master%20regulator%20for%20the%20proliferation%20and%20function%20of%20Th17%20cells%2C%20could%20be%20an%20effective%20alternative.%20However%2C%20oral%20ROR%5Cu03b3%20antagonists%20%28VTP43742%2C%20TAK828%29%20with%5Cu00a0high%20systemic%20exposure%20showed%20toxicity%20in%20phase%20I%5C%2FII%20clinical%20trials%20and%20terminated%20development.%20To%20alleviate%20the%20potential%20safety%20concerns%2C%20identifying%20compounds%20with%20skin-restricted%20exposure%20amenable%20for%20topical%20use%20is%20of%20great%20interest.%20Systematic%20structure%20activity%20relationship%20study%20and%20multi-parameter%20optimization%20led%20to%20the%20discovery%20of%20a%20novel%20ROR%5Cu03b3%20antagonist%20%28SHR168442%29%20with%20desired%20properties%20for%20a%20topical%20drug.%20It%20suppressed%20the%20transcription%20of%20IL-17%20gene%2C%20leading%20to%20reduction%20of%20IL-17%20cytokine%20secretion.%20It%20showed%20high%20exposure%20in%20skin%2C%20but%20low%20in%20plasma.%20Topical%20application%20of%20SHR168442%5Cu00a0in%20Vaseline%20exhibited%20excellent%20efficacy%20in%20the%20imiquimod-induced%20and%20IL-23-induced%20psoriasis-like%20skin%20inflammation%20mouse%20models%20and%20correlated%20with%20the%20reduction%20of%20Th17%20pathway%20cytokines%2C%20IL-6%2C%20TNF%5Cu03b1%20and%20IL-17A.%20This%20work%20demonstrated%20restricted%20skin%20exposure%20of%20ROR%5Cu03b3%20antagonist%20may%20provide%20a%20new%20topical%20treatment%20option%20as%20targeted%20therapeutics%20for%20mild%20to%20moderate%20psoriasis%20patients%20and%20may%20be%20suitable%20for%20the%20treatment%20of%20any%20other%20inflammatory%20disorders%20that%20are%20accessible%20locally.%22%2C%22date%22%3A%222021-04-28%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1038%5C%2Fs41598-021-88492-1%22%2C%22ISSN%22%3A%222045-2322%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs41598-021-88492-1%22%2C%22deleted%22%3A1%2C%22collections%22%3A%5B%22DUPVZUHA%22%5D%2C%22dateModified%22%3A%222021-04-28T16%3A36%3A43Z%22%7D%7D%5D%7D
Liu, S., Liu, D., Shen, R., Li, D., Hu, Q., Yan, Y., Sun, J., Zhang, F., Wan, H., Dong, P., Feng, J., Zhang, R., Li, J., Zhang, L., & Tao, W. (2021). Discovery of a novel RORγ antagonist with skin-restricted exposure for topical treatment of mild to moderate psoriasis. Scientific Reports, 11(1), 9132. https://doi.org/10.1038/s41598-021-88492-1 Cite
Full Article
Exit mobile version