Description
AZD8055 (1009298-09-2) is a potent and highly selective inhibitor of mammalian target of rapamycin kinase (mTOR) kinase (IC50 = 0.8 nM).1,2 ?mTOR acts as a nutrient/energy/redox sensor and a controller of protein synthesis – as such it is a very important target for cancer research.? It has been investigated as a potential chemotherapeutic for various cancers.3-7
Uses
A novel ATP-competitive inhibitor of mTOR with an IC50 of 0.8 nM.
Uses
A potent, selective, and orally bioavailable ATP-competitive mTOR kinase inhibitor with an IC50 of 0.8 nM. It inhibits the phosphorylation of mTORC1 substrates p70S6K and 4E-BP1 as well as phosphoryla
tion of the mTORC2 substrate AKT and downstream proteins. The rapamycin-resistant T37/46 phosphorylation sites on 4E-BP1 were fully inhibited by AZD8055, resulting in significant inhibition of cap-dep
endent translation. In vitro, AZD8055 potently inhibits proliferation and induces autophagy in H838 and A549 cells. In vivo, AZD8055 induces a dose-dependent pharmacodynamic effect on phosphorylated S
6 and phosphorylated AKT at plasma concentrations leading to tumor growth inhibition.
Definition
ChEBI: AZD-8055 is a pyridopyrimidine that is pyrido[2,3-d]pyrimidine which is substituted at positions 2 and 4 by (3S)-3-methylmorpholin-4-yl groups and at position 5 by a 3-(hydroxymethyl)-4-methoxyphenyl group. It is an mTOR complex 1/2 (mTORC1/2) dual inhibitor [mTOR = mammalian target of rapamycin]. It has a role as a mTOR inhibitor, an apoptosis inducer and an antineoplastic agent. It is a member of benzyl alcohols, a tertiary amino compound, a pyridopyrimidine and a member of morpholines.
target
mTOR (full length)
References
1) Chresta et al. (2010), AZD8055 is a potent, selective, and orally bioavailable ATP-competitive mammalian target of rapamycin kinase inhibitor with in vitro and in vivo antitumor activity; Cancer Res. 70 288
2) Pike et al. (2013), Optimization of potent an selective dual mTORC1 and mTORC2 inhibitors: the discovery of AZD8055 and AZD2014; Bioorg. Med. Chem. Lett. 23 1212
3) Holt et al. (2012), Enhanced apoptosis and tumor growth suppression elicited by combination of MEK (selumetinib) and mTOR kinase inhibitors (AZD8055); Cancer Res. 72 1804
4) Willems et al. (2012), The dual mTORC1 and mTORC2 inhibitor AZD8055 has anti-tumor activity in acute myeloid leukemia; Leukemia 26 1195
5) Li et al. (2013),The mTOR inhibitor AZD8055 inhibits proliferation and glycolysis in cervical cancer cells; Oncol. Lett. 5 717
6) Li et al. (2013), The dual mTORC1 and mTORC2 inhibitor AZD8055 inhibits head and neck squamous cell carcinoma cell growth in vivo and in vitro; Biochem. Biophys. Res. Commun. 440 701
7) Hu et al. (2014), AZD8055 induces cell death associated with autophagy and activation of AMPK in hepatocellular carcinoma; Oncol. Rep. 31 649
