Metabolism - Pyruvate dehydrogenases (PDH) - Phospholipases - sterol demethylase - PC-PLC
Glucose metabolism plays a significant role in cell proliferation, growth, survival, and tumorgenesis. Hormones such as insulin regulate the maintenance of glucose homeostasis. Insulin binding to the insulin receptor (IR) activates the insulin receptor substrate (IRS) protein, followed by the activation of PI3K/Akt and Erk1/2 signaling pathways, leads to the translocation of Glut4 vesicles, glucose uptake, cell proliferation and survival. Abnormal insulin signaling is implicated in diabetes, obesity, atherosclerosis and neurodegenerative disease etc.
Serine/threonine kinase AMPK upregulates glucose uptake by promoting the expression and function of glucose transporters. AMPK is activated by increased AMP/ATP ratio, resulting from cellular and environmental stress, e.g. low glucose, heat shock, hypoxia and ischemia. AMPK activation positively modulates signaling transductions that refill ATP levels. Moreover, it also stimulates catabolic processes such as fatty acid oxidation and glycolysis through inhibition of ACC and activation of PFK2. AMPK negatively regulates various proteins which are important to ATP-consuming mechanisms, e.g. mTORC2, glycogen synthase, SREBP-1, and TSC2, causing the downregulation/inhibition of gluconeogenesis and glycogen, lipid and protein synthesis.
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- B3422 U-731221 CitationTarget: PC-PLCSummary: 磷脂酶C,磷脂酶A2和5-LO(5-脂氧合酶)抑制剂
- A1718 Posaconazole中文名: 泊沙康唑Target: Cytochrome P450 (CYP450)|sterol demethylaseSummary: 甾醇 C14ɑ去甲基化酶抑制剂
- A4356 Varespladib (LY315920)中文名: 伐瑞拉迪Target: PhospholipasesSummary: HnsPLA的强效选择性抑制剂
- A4333 CPI-6131 CitationTarget: Pyruvate dehydrogenases (PDH)Summary: PDH/α-KGDH抑制剂