CS12192 Reverses Alopecia Areata by Selectively Targeting JAK3/JAK1/TBK1 DOI Open Access
Hui Jin, Zongyang Li,

Xinwen Li

et al.

Advanced Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 28, 2025

Abstract The approval of JAK inhibitors, represented by baricitinib, for the treatment alopecia areata (AA) has ushered in a new era. However, their excessive immunosuppressive effects have also raised numerous concerns. Therefore, development inhibitors with different selectivities may enhance drug safety while maintaining therapeutic efficacy. CS12192, developed our team, is selective JAK3 inhibitor that partially inhibits JAK1 and TBK1. In this study, we evaluate effectiveness CS12192 baricitinib C3H/HeJ skin‐transplanted AA mouse model conduct in‐depth analysis similarities differences mechanisms two compounds using mass cytometry (CyTOF) RNA‐seq technology. results show could reverse hair growth inhibition mice dose‐dependent manner, high‐dose group exhibiting comparable to but better safety. Further research revealed both significantly reduced infiltration immune cells, particularly CD8 + T skin animals. CyTOF mechanistic between regulating AA‐related cells signaling pathways. conclusion, as novel inhibitor, holds great potential AA.

Language: Английский

TANK-Binding Kinase 1 in the Pathogenesis and Treatment of Inflammation-Related Diseases DOI Open Access
Hui Lü, Xiaolin Chen,

Mengke Huang

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 1941 - 1941

Published: Feb. 24, 2025

TANK-binding kinase 1 (TBK1) is a key signaling involved in innate immune and inflammatory responses. TBK1 drives cells to participate the response by activating NF-κB interferon regulatory factor pathways cells, promoting expression of pro-inflammatory genes, regulating cell function. Thus, it plays crucial role initiating cascade that establishes an environment. In inflammation-related diseases, acts as bridge linking inflammation immunity, metabolism, or tumorigenesis, playing important pathogenesis immune-mediated metabolic, syndromes, inflammation-associated cancers activation production cytokines cells. this review, we focused on mechanisms inflammatory-related providing new insights for further studies targeting potential treatment diseases. optimizing investigating highly selective cell-specific inhibitors their application these

Language: Английский

Citations

0
CS12192 Reverses Alopecia Areata by Selectively Targeting JAK3/JAK1/TBK1 DOI Open Access
Hui Jin, Zongyang Li,

Xinwen Li

et al.

Advanced Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 28, 2025

Abstract The approval of JAK inhibitors, represented by baricitinib, for the treatment alopecia areata (AA) has ushered in a new era. However, their excessive immunosuppressive effects have also raised numerous concerns. Therefore, development inhibitors with different selectivities may enhance drug safety while maintaining therapeutic efficacy. CS12192, developed our team, is selective JAK3 inhibitor that partially inhibits JAK1 and TBK1. In this study, we evaluate effectiveness CS12192 baricitinib C3H/HeJ skin‐transplanted AA mouse model conduct in‐depth analysis similarities differences mechanisms two compounds using mass cytometry (CyTOF) RNA‐seq technology. results show could reverse hair growth inhibition mice dose‐dependent manner, high‐dose group exhibiting comparable to but better safety. Further research revealed both significantly reduced infiltration immune cells, particularly CD8 + T skin animals. CyTOF mechanistic between regulating AA‐related cells signaling pathways. conclusion, as novel inhibitor, holds great potential AA.

Language: Английский

Citations

0