PI3K/Akt/mTOR Signaling - Ovarian Cancer - Cancer - Hepatocellular Carcinoma
The PI3K/Akt/mTOR signaling pathway is a key regulator in growth, survival, cell cycle proliferation, protein synthesis and glucose metabolism. Growth factors, hormones, and cytokines can activate this pathway by binding their cognate receptor tyrosine kinase (RTK), cytokine receptor, or GPCR, resulting in the activation of lipid kinase PI3K which produces PIP3 at the plasma membrane.
The binding of PIP3 translocates Akt to cell membranes, enables Akt activation through phosphorylation at Thr308 mediated by phosphoinositide dependent kinase 1 (PDK1). In addition, Akt is phosphorylated at Ser473 by the mTOR-rictor complex, mTORC2. PTEN is a negative regulator of Akt signaling that reverses the function of PI3K by removing 3’-phosphate groups. Akt activity is also negatively regulated by the phosphatases PP2A and PHLPP. Akt propagates its signal to affect DNA transcription, cell cycle and apoptosis. Akt can activate mTOR directly by phosphorylation or indirectly, by phosphorylation and inactivation of mTOR inhibitor TSC2 and PRAS40. Together these mechanisms stimulate cell growth and G1 cell cycle progression through signaling via p70 S6 Kinase and inhibition of 4E-BP1. Defects in PI3K/AKT/mTOR signaling are implicated in cancer, diabetes and cardiovascular disease etc.
- B2228 PF-47086711 CitationTarget: p70 rskSummary: P70 S6K1亚型抑制剂
- B1321 OTSSP167Target: MELKSummary: MELK抑制剂
- B2178 BAY 80-6946 (Copanlisib)1 Citation中文名: 库潘尼西Target: PI3KSummary: PI3K抑制剂
- B2186 GSK2636771Target: PI3KSummary: PIK3抑制剂
- B1047 GDC-0032Target: PI3KSummary: PI3Kα 抑制剂
- B2176 GSK1059615Target: PI3K|mTORSummary: PI3K和mTOR抑制剂
- B2172 PP121Target: mTOR|Eph Receptors|VEGFR|PDGFR|Bcr-Abl|Src|DNA-PK|P110|HckSummary: 酪氨酸激酶和磷酸肌醇激酶双重抑制剂
- B1642 WYE-125132 (WYE-132)Target: mTORSummary: mTOR抑制剂
- A8616 A-674563Target: Cyclin-Dependent Kinases|Akt|GSK-3|ERK|PKC|PKA|RSKSummary: Akt1 / PKA / CDK2的强效选择性抑制剂
- A8556 GSK21264581 CitationTarget: PI3K|mTORSummary: PI3K/mTOR抑制剂