Selonsertib (GS-4997), an orally bioavailable, selective apoptosis signal-regulating kinase 1 (ASK1) inhibitor with a pIC50 of 8.3, has been evaluated as an experimental treatment for diabetic nephropathy and kidney fibrosis.

Selonsertib (GS-4997) 是一种具有高度选择性的、有效的 ASK1 抑制剂，具有潜在的消炎、抗肿瘤的、抗纤维化活性。 GS-4997具有生物口服活性。 口服给药后，GS-4997靶向并与ASK1的催化激酶区域以ATP竞争性方式结合，抑制其磷酸化和激活。 GS-4997抑制ASK1下游激酶的磷酸化，如c-Jun N-terminal kinases (JNKs) 、p38 MAPK。 通过抑制ASK1依赖性的信号转导通路的激活，GS-4997可阻止炎性细胞因子的生成、 下调参与纤维化过程的基因表达、抑制过度凋亡、细 …

Selonsertib, a serine/threonine kinase inhibitor, targets apoptosis signal-regulating kinase 1 (ASK1) and is now in phase III clinical trial for the treatment of non-alcoholic steatohepatitis (NASH). In this study, we investigated whether selonsertib could reverse MDR-mediated by ABC transporters, including ABCB1, ABCG2, ABCC1 and ABCC10.

By preventing the activation of ASK1-dependent signal transduction pathways, GS-4997 prevents the production of inflammatory cytokines, down-regulates the expression of genes involved in fibrosis, suppresses excessive apoptosis and inhibits cellular proliferation.

Selonsertib (GS-4997), a selective ASK1 inhibitor, has been found to significantly improve metabolic parameters associated with nonalcoholic steatohepatitis (NASH) and to reduce hepatic steatosis, inflammation, as well as fibrosis. Its phase III clinical trial has been initiated by the U.S. Food and Drug Administration (FDA) [24–26]. In this ...

Selonsertib (GS-4997) is an apoptosis signal-regulating kinase 1 (ASK1) inhibitor. ASK1, a redox-sensitive mitogen-activated protein kinase kinase kinase, functions as a key signaling node by promoting deleterious effects.

Selonsertib（GS-4997）是一种可口服的选择性凋亡信号调节激酶 1（ASK1）抑制剂，其 pIC50 值为 8.3，已被评估用于糖尿病肾病和肾脏纤维化的实验性治疗。 生物相关数据

Selonsertib hydrochloride (GS-4997 hydrochloride) is an orally bioavailable enzyme inhibitor with potential anti-inflammatory, anti-tumor and anti-fibrotic activities. Selonsertib hydrochloride blocks ASK1 phosphorylation and activation by binding to the catalytic kinase domain.

Selonsertib（也称为 GS-4997）是一种高度选择性、有效的每日一次口服 ASK1（凋亡信号调节激酶 1）抑制剂，pIC50 为 8.3±0.07。 Selonsertib 因其潜在的抗炎、抗癌和抗纤维化作用而被研究为糖尿病肾病和肾纤维化的潜在治疗方法。 细胞凋亡信号调节激酶 1 (ASK1/MAP3K) 是有丝分裂原激活蛋白激酶家族的成员，与急性缺血/再灌注损伤有关。 Selonsertib 是通过基于结构的药物设计、解构和重新优化著名的 ASK1 抑制剂而发现的。 在孤立性灌注心脏损伤模型 …