| 产品介绍 |
AZD8055是ATP竞争性mTOR抑制剂，IC50为0.8 nM，比对PI3K和ATM/DNA-PK的抑制性强超过1000倍。 |
| 备注 |
AZD8055 is a novel ATP-competitive mTOR inhibitor with IC50 of 0.8 nM with excellent selectivity (?1,000-fold) against PI3K isoforms and ATM/DNA-PK. Phase 1. |
| 生化机理 |
AZD8055 shows low activity (～1,000-fold) against all PI3K isoforms (α, β, γ, δ) and other members of the PI3K-like kinase family (ATM and DNA-PK). AZD8055 inhibits the phosphorylation of mTORC1 (p70S6K and 4E-BP1) as well as phosphorylation of the mTORC2 (Akt) and downstream proteins. The rapamycin-resistant T37/46 phosphorylation sites on 4E-BP1 can be fully inhibited by AZD8055, resulting in significant inhibition of cap-dependent translation. AZD8055 potently inhibits proliferation in U87MG, A549 and H838 cells with IC50 of 53, 50 and 20 nM, respectively. AZD8055 also induces autophagy and increased LC3-II levels in H838 and A549 cells [1]. AZD8055 decreases AML blast cell proliferation and cell cycle progression, reduces the clonogenic growth of leukemic progenitors and induces caspase-dependent apoptosis in leukemic cells but not in normal immature CD34+ cells |
| 别名 |
(5-(2,4-二((3S)-3-甲基吗啉-4-基)吡啶并(2,3-d)嘧啶-7-基)-2-甲氧基苯基)甲醇;;AZD8055; AZD 8055;(5-(2,4-bis((3s)-3-methylmorpholin-4-yl)pyrido(2,3-d)pyrimidin-7-yl)-2-methoxyphenyl)methanol |
