CS12192, a novel JAK3/JAK1/TBK1 inhibitor, attenuates autoimmune dermatoses in murine models.

Objective: Autoimmune dermatosis (AID) occurs when the body's immune system attacks skin or tissue, leading to various types of skin disorders or injuries. Recent studies show that Janus kinases (JAKs) play critical roles in autoimmune diseases including AID by regulating multiple cytokine signaling pathways. CS12192, a novel JAK3/JAK1/TBK1 inhibitor, has been reported to exert ameliorative effects in rheumatoid arthritis.

Targeting ASK1 by CS17919 alleviates kidney- and liver-related diseases in murine models.

Background: Apoptosis signal-regulating kinase 1 (ASK1) is a MAP3K kinase in the MAPK signaling pathway activated by stressors and triggers downstream biological effects such as inflammation and apoptosis; therefore, inhibition of ASK1 kinase activity can protect cells from pathological injury. In this study, we designed and synthesized a novel selective ASK1 inhibitor, CS17919, and investigated its pharmacological effects in various animal models of metabolic injury.

Methods: First, we validated the ability of CS17919 to inhibit ASK1 in vitro and then tested the safety profile of CS17919 in cell lines compared with Selonsertib (GS-4997), a phase III ASK1 inhibitor.

CS27109, A Selective Thyroid Hormone Receptor- Agonist Alleviates Metabolic-Associated Fatty Liver Disease in Murine Models.

Background/aim: Thyroid hormone receptor- (THR-) agonists play crucial roles in dyslipidemia and metabolic associated fatty liver disease (MAFLD). We developed a novel oral and liver-targeted THR- agonist, CS27109, and evaluated its efficacy in the treatment of metabolic disorders.

Materials And Methods: We evaluated and efficacy and/or safety of CS27109 along with MGL3196 (a phase III THR- agonist).