1009298-09-2

Basic information

• Product Name: AZD-8055
• Synonyms: AZD 8055 [5-[2,4-Bis((3S)-3-methylmorpholin-4-yl)pyrido[2,3-d]pyrimidin-7-yl]-2-methoxyphenyl]methanol;AZD8055, >=98%;AZD-8055;[5-[2,4-Bis((3S)-3-methylmorpholin-4-yl)pyrido[2,3-d]pyrimidin-7-yl]-2-methoxyphenyl]methanol;Propanoic acid, 2,2-dimethyl-, [5-(2,4-dichloropyrido[2,3-d]pyrimidin-7-yl)-2-methoxyphenyl]methyl ester;(5-{2,4-dichloropyrido[2,3-d]pyriMidin-7-yl}-2-Methoxyphenyl)Methyl 2,2-diMethylpropanoate;[5-[2,4-Bis((3S)-3-MethylMorpholin-4-yl)pyrido[;5-[2,4-Bis[(3S)-3-Methyl-4-Morpholinyl]pyrido[2,3-d]pyriMidin-7-yl]-2-MethoxybenzeneMethanol
• CAS NO: 1009298-09-2
• Molecular Formula: C25H31N5O4
• Molecular Weight: 465.54474
• EINECS: -0
• Product Categories: Inhibitors;Akt;mTOR;PI3K;Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Protein Kinase Inhibitors and Activators;PI3K/Akt/mTOR
• Mol File: 1009298-09-2.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 694.302 °C at 760 mmHg
• Flash Point: 373.701 °C
• Appearance: /
• Density: 1.248
• Storage Temp.: -20°C
• Solubility: Soluble in DMSO (up to 30 mg/ml)
• PKA: 14.20±0.10(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 2 months.
• CAS DataBase Reference: AZD-8055(CAS DataBase Reference)
• NIST Chemistry Reference: AZD-8055(1009298-09-2)
• EPA Substance Registry System: AZD-8055(1009298-09-2)

Safety Data

• Safety Statements: 24/25
• Hazardous Substances Data: 1009298-09-2(Hazardous Substances Data)

Usage

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

Different sources of media describe the Uses of 1009298-09-2 differently. You can refer to the following data:
1. A novel ATP-competitive inhibitor of mTOR with an IC50 of 0.8 nM.
2. 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.

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

Upstream product

• 1009303-42-7 (S)-4-(2,7-dichloropyrido[2,3-d]pyrimidin-4-yl)-3-methylmorpholine 
• 58584-92-2 2-amino-6-chloronicotinic acid 
• 938443-20-0 2,4,7-trichloropyrido[2,3-d]pyrimidine 
• 938443-19-7 7-chloropyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione 
• 64321-24-0 2-amino-6-chloro-pyridine-3-carboxamide 
• 38496-18-3 2,6-dichloropyridine-3-carboxylic acid 
• 1201798-98-2 5-{2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl}-2-methoxybenzyl pivalate 
• 1009298-82-1 methyl 5-{2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl}-2-methoxybenzoate 
• 1009303-44-9 (3S)-4-[7-chloro-2-[(3S)-3-methylmorpholin-4-yl]pyrido[2,3-d] pyrimidin-4-yl] 3-methyl-morpholine 
• 1009303-77-8 [2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methanol 

Relevant articles and documents

Optimization of potent and selective dual mTORC1 and mTORC2 inhibitors: The discovery of AZD8055 and AZD2014

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

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