1009298-09-2 Usage
Description
AZD-8055 is a potent and highly selective inhibitor of mammalian target of rapamycin kinase (mTOR) with an IC50 of 0.8 nM. It acts as a nutrient/energy/redox sensor and a controller of protein synthesis, making it an important target for cancer research.
Used in Pharmaceutical Industry:
AZD-8055 is used as a chemotherapeutic agent for various cancers due to its ability to inhibit the phosphorylation of mTORC1 substrates p70S6K and 4E-BP1, as well as the phosphorylation of the mTORC2 substrate AKT and downstream proteins. This results in significant inhibition of cap-dependent translation and tumor growth.
AZD-8055 is also used as an ATP-competitive inhibitor of mTOR kinase, which makes it a potential treatment for cancers that have developed resistance to rapamycin, a commonly used mTOR inhibitor. In vitro, AZD-8055 potently inhibits proliferation and induces autophagy in cancer cells, while in vivo, it induces a dose-dependent pharmacodynamic effect on phosphorylated S6 and phosphorylated AKT at plasma concentrations, leading to tumor growth inhibition.
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
Check Digit Verification of cas no
The CAS Registry Mumber 1009298-09-2 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,0,0,9,2,9 and 8 respectively; the second part has 2 digits, 0 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 1009298-09:
(9*1)+(8*0)+(7*0)+(6*9)+(5*2)+(4*9)+(3*8)+(2*0)+(1*9)=142
142 % 10 = 2
So 1009298-09-2 is a valid CAS Registry Number.
1009298-09-2Relevant articles and documents
Optimization of potent and selective dual mTORC1 and mTORC2 inhibitors: The discovery of AZD8055 and AZD2014
Pike, Kurt G.,Malagu, Karine,Hummersone, Marc G.,Menear, Keith A.,Duggan, Heather M.E.,Gomez, Sylvie,Martin, Niall M.B.,Ruston, Linette,Pass, Sarah L.,Pass, Martin
, p. 1212 - 1216 (2013/03/14)
The optimization of a potent and highly selective series of dual mTORC1 and mTORC2 inhibitors is described. An initial focus on improving cellular potency whilst maintaining or improving other key parameters, such as aqueous solubility and margins over hERG IC50, led to the discovery of the clinical candidate AZD8055 (14). Further optimization, particularly aimed at reducing the rate of metabolism in human hepatocyte incubations, resulted in the discovery of the clinical candidate AZD2014 (21).
2-METHYLMORPHOLINE PYRIDO-, PYRAZO- AND PYRIMIDO-PYRIMIDINE DERIVATIVES AS MTOR INHIBITORS
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Page/Page column 122; 128, (2008/06/13)
There is provided a compound of Formula (I), or a pharmaceutically acceptable salt thereof. There are also provided processes for the manufacture of a compound of Formula (1), and the use of a compound of Formula (1) as a medicament and in the treatment of cancer
