Metabolism - Pancreatic Cancer - Bladder Cancer - Breast Cancer - Type 2 Diabetes
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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- A8721 CBR-58841 CitationTarget: 3-phosphoglycerate dehydrogenaseSummary: PHGDH抑制剂
- B4900 Indoximod (NLG-8189)Summary: 吲哚胺2,3-双加氧酶(IDO)途径抑制剂
- B7794 BMS 3094032 CitationTarget: Fatty-acid-binding proteins (FABPs)Summary: FABP4抑制剂
- B1943 Fenofibrate1 Citation中文名: 非诺贝特Summary: PPARα激动剂
- A8333 Canagliflozin1 Citation中文名: 卡格列净Target: SGLTSummary: SGLT2的有效选择性抑制剂
- A4358 U-104Target: Carbonic AnhydrasesSummary: CAIX抑制剂
- A4347 Methotrexate2 Citation中文名: 甲氨蝶呤Target: Folate AnalogueSummary: 叶酸拮抗剂,抑制DFHR。
- A4346 Aminophylline中文名: 氨茶碱,氨基非林Target: Phosphodiesterases (PDEs)Summary: Pan-PDE抑制剂
- A4324 Pioglitazone HCl中文名: 盐酸吡格列酮Summary: PPARγ激动剂
- A4316 Ketoconazole中文名: 酮康唑Target: Cytochrome P450 (CYP450)Summary: 环孢菌素氧化酶和睾酮6β-羟化酶的抑制剂