Kaisi Kaidi (Shanghai) Pharmaceutical Technology Co., Ltd. (Kaisi Kaidi (Shanghai) Pharmaceutical Technology Co., Ltd.)

概览

疾病领域	数量

内分泌与代谢疾病	1

排名前五的药物类型	数量

小分子化药	1

排名前五的靶点	数量

THR-β(甲状腺激素受体β)	1

关联

1

项与 Kaisi Kaidi (Shanghai) Pharmaceutical Technology Co., Ltd. 相关的药物

CS-060380

靶点

THR-β

作用机制

THR-β激动剂

在研机构

凯思凯迪(上海)医药科技有限公司 [+1]

原研机构

凯思凯迪(上海)医药科技有限公司

在研适应症

高低密度脂蛋白胆固醇血症 [+1]

非在研适应症-

最高研发阶段临床1期

首次获批国家/地区-

首次获批日期-

1

项与 Kaisi Kaidi (Shanghai) Pharmaceutical Technology Co., Ltd. 相关的临床试验

NCT06573528 / Not yet recruiting临床1期

A Phase I Study Evaluating the Safety, Tolerability, Pharmacokinetics and Food Effect of Randomized, Double-Blind, Placebo-Controlled Single and Multiple Dose Escalations of CS060380 in Healthy and Elevated LDL-C Subjects

Study to Evaluate Safety, Tolerability and Pharmacokinetics of CS060380 in Healthy and Elevated LDL-C Subjects.

开始日期2024-08-30

申办/合作机构

Kaisi Kaidi (Shanghai) Pharmaceutical Technology Co., Ltd.

100 项与 Kaisi Kaidi (Shanghai) Pharmaceutical Technology Co., Ltd. 相关的临床结果

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0 项与 Kaisi Kaidi (Shanghai) Pharmaceutical Technology Co., Ltd. 相关的专利（医药）

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1

项与 Kaisi Kaidi (Shanghai) Pharmaceutical Technology Co., Ltd. 相关的文献（医药）

Acta Pharmacologica Sinica

FXR activation remodels hepatic and intestinal transcriptional landscapes in metabolic dysfunction-associated steatohepatitis

Article

作者: Wang, Gai-Hong ; Zhang, Meng-Jiao ; Zou, Zi-Yuan ; Zhao, Guan-Guan ; Fan, Jian-Gao ; Xie, Cen ; Wen, Ying-Quan ; Zheng, Dong-Xuan ; Zhang, Yong-Xin ; Shi, Jing-Jing ; Song, Ye-Yu ; Duan, Xiao-Qun ; Liu, Ya-Meng ; Gonzalez, Frank J ; Chen, Ru-Ye ; Wang, Hui-Xia ; Wang, Yuan-Yang

The escalating obesity epidemic and aging population have propelled metabolic dysfunction-associated steatohepatitis (MASH) to the forefront of public health concerns. The activation of FXR shows promise to combat MASH and its detrimental consequences. However, the specific alterations within the MASH-related transcriptional network remain elusive, hindering the development of more precise and effective therapeutic strategies. Through a comprehensive analysis of liver RNA-seq data from human and mouse MASH samples, we identified central perturbations within the MASH-associated transcriptional network, including disrupted cellular metabolism and mitochondrial function, decreased tissue repair capability, and increased inflammation and fibrosis. By employing integrated transcriptome profiling of diverse FXR agonists-treated mice, FXR liver-specific knockout mice, and open-source human datasets, we determined that hepatic FXR activation effectively ameliorated MASH by reversing the dysregulated metabolic and inflammatory networks implicated in MASH pathogenesis. This mitigation encompassed resolving fibrosis and reducing immune infiltration. By understanding the core regulatory network of FXR, which is directly correlated with disease severity and treatment response, we identified approximately one-third of the patients who could potentially benefit from FXR agonist therapy. A similar analysis involving intestinal RNA-seq data from FXR agonists-treated mice and FXR intestine-specific knockout mice revealed that intestinal FXR activation attenuates intestinal inflammation, and has promise in attenuating hepatic inflammation and fibrosis. Collectively, our study uncovers the intricate pathophysiological features of MASH at a transcriptional level and highlights the complex interplay between FXR activation and both MASH progression and regression. These findings contribute to precise drug development, utilization, and efficacy evaluation, ultimately aiming to improve patient outcomes.

100 项与 Kaisi Kaidi (Shanghai) Pharmaceutical Technology Co., Ltd. 相关的药物交易

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100 项与 Kaisi Kaidi (Shanghai) Pharmaceutical Technology Co., Ltd. 相关的转化医学

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