PI3K/Akt/mTOR Signaling
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.
- B5831 Acalisib (GS-9820)Target: PI3KSummary: PI3Kδ抑制剂
- B5815 LY2584702Target: p70 rskSummary: P70 S6激酶抑制剂
- B4991 GNE-317Summary: 脑通透性PI3K抑制剂
- B4903 CX-4945 sodium saltSummary: CK2抑制剂
- B4898 BikininTarget: GSK-3Summary: GSK3抑制剂和油菜素类固醇激活剂
- B4840 ZLN024 hydrochlorideSummary: 新型AMPK变构激活剂
- B4811 Afuresertib中文名: 阿氟色替Summary: 泛AKT抑制剂
- B8001 GNE-477Summary: PI3K/mTOR双重抑制剂
- B8000 GNE-493Summary: Pan-PI3K/mTOR抑制剂
- A8890 HTH-01-015Target: NUAKSummary: NUAK1抑制剂