scd1 in hepg2 cell

XEN723 是新型的硬脂酰辅酶 A 去饱和酶的噻唑基咪唑烷酮抑制剂，能够抑制小鼠和 HepG2 细胞的活性，它们的 IC50值分别为 45 和 524 nM。

MK-8245 trifluoroacetate is a liver-targeting inhibitor of stearoyl-CoA desaturase (SCD) with IC50 of 1 nM for human SCD1 and 3 nM for both rat SCD1 and mouse SCD1, with anti-diabetic and anti-dyslipidemic efficacy. IC50 value: 1 nM (hSCD1) Target: SCD1 in vitro: MK-8245, a phenoxy piperidine isoxazole derivative, has been identified as a potent and liver-specific SCD inhibitor. It contains a tetrazole acetic acid moiety, which is the key molecule for OATPs recognition and liver-targeting. MK-8245 displays similar potencies against human, rat and mouse SCD1 with IC50 values of 1 nM for human SCD1 and 3 nM for both rat SCD1 and mouse SCD1. MK-8245 exhibits a significant SCD inhibition in the rat hepatocyte assay which contains functional, active OATPs with IC50 of 68 nM, while being only weakly active in the HepG2 cell assay which is devoid of active OATPs with IC50 of ~1 μM. MK-8245 displays highly selective activity for the Δ-5 and Δ-6 desaturases (i.e., >100000 μM vs rat and human Δ5D and Δ6D as assessed in the HepG assay. in vivo: Administration of MK-8245 at 10 mg kg in mice exhibits a tissue distribution profile concentrated in the liver. It shows a liver-to-Harderian gland ratio of 21, suggesting a high degree of liver-targeting compared to a systemically distributed compound with liver-to-Harderian gland ratio of 1.5. Oral dosing of MK-8245 in mice, rats, dogs, and rhesus monkeys demonstrates that MK-8245 is distributed mainly to the liver, with low exposure in tissues associated with potential adverse events. The liver-to-skin ratios are >30:1 in all four species. Administration of MK-8245 to eDIO mice before the glucose challenge improves glucose clearance in a dose-dependent manner with ED50 of 7 mg kg.

Agrimonolide 是一种来自异香豆素的化合物，主要存在于草药Agrimonia pilosa Ledeb 中，具有显著的生物活性。Agrimonolide 通过抑制脂多糖（LPS）诱导的JAK-STATs 和p38 MAPKs 信号通路的激活而发挥抗炎作用。Agrimonolide 及其衍生物去甲阿戈莫内德已显示出能够有效提高肝细胞中胰岛素介导的糖原水平，可能在调节胰岛素抵抗的HepG2细胞中发挥关键作用。Agrimonolide 通过靶向卵巢癌细胞中的SCD1，对癌症的进展和诱导细胞死亡和凋亡表现出抑制作用。特别是，Agrimonolide 对A2780和SKOV-3细胞的增殖、迁移和侵袭表现出剂量依赖性的抑制，同时促进细胞凋亡。该化合物还被发现能诱导铁介导的细胞死亡，同时增加活性氧（ROS）和总铁的水平。Agrimonolide 很容易穿过血脑屏障，表明其在神经系统疾病的治疗应用方面具有潜力。