{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T02:03:20Z","timestamp":1774317800777,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T00:00:00Z","timestamp":1718323200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Apoptosis signal\u2010regulating 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>First, we validated the ability of CS17919 to inhibit ASK1 in\u00a0vitro and then tested the safety profile of CS17919 in cell lines compared with Selonsertib (GS\u20104997), a phase III ASK1 inhibitor. We then conducted pharmacokinetic (PK) studies in mice. Finally, we tested the in\u00a0vivo efficacy of CS17919 in murine models of chronic kidney disease (CKD) and non\u2010alcoholic steatohepatitis (NASH).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to GS\u20104997, CS17919 demonstrated comparable inhibition of ASK1 in\u00a0vitro, exhibited lower toxicity, and provided greater protection in palmitic acid\u2010treated LO2 cells. CS17919 also showed pronounced pharmacokinetic properties such as a high plasma concentration. In the unilateral ureteral obstruction model (UUO), CS17919 and GS\u20104997 preserved kidney function and showed a non\u2010significant tendency to alleviate kidney fibrosis. In the diabetic kidney disease (DKD) model, CS17919 significantly improved serum creatinine and glomerular sclerosis. In the NASH model, the combination of CS17919 and a THR\u03b2 agonist (CS27109) was found to significantly improve liver inflammation and substantially reduced liver fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>CS17919 showed cell protective, anti\u2010inflammatory, and antifibrotic effects in\u00a0vitro and in\u00a0vivo, suggesting its therapeutic potential for metabolic\u2010related kidney and liver diseases.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ame2.12437","type":"journal-article","created":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T09:14:18Z","timestamp":1718356458000},"page":"102-113","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Targeting <scp>ASK1<\/scp> by <scp>CS17919<\/scp> alleviates kidney\u2010 and liver\u2010related diseases in murine models"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4923-5110","authenticated-orcid":false,"given":"Guoqiang","family":"Liao","sequence":"first","affiliation":[{"name":"Chengdu Chipscreen Pharmaceutical Corp., Ltd.  Chengdu Sichuan P.R. China"},{"name":"Laboratory of Experimental Animal Disease Model College of Veterinary Medicine, Sichuan Agricultural University  Chengdu Sichuan P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qianjiao","family":"Yang","sequence":"additional","affiliation":[{"name":"Shenzhen Chipscreen Biosciences Co., Ltd.  Shenzhen Guangdong P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuhua","family":"Mao","sequence":"additional","affiliation":[{"name":"Chengdu Chipscreen Pharmaceutical Corp., Ltd.  Chengdu Sichuan P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiru","family":"Zhao","sequence":"additional","affiliation":[{"name":"Chengdu Chipscreen Pharmaceutical Corp., Ltd.  Chengdu Sichuan P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beizhong","family":"Chen","sequence":"additional","affiliation":[{"name":"Chengdu Chipscreen Pharmaceutical Corp., Ltd.  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China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengjian","family":"Huang","sequence":"additional","affiliation":[{"name":"Chengdu Chipscreen Pharmaceutical Corp., Ltd.  Chengdu Sichuan P.R. China"},{"name":"Shenzhen Chipscreen Biosciences Co., Ltd.  Shenzhen Guangdong P.R. 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