AZD-8055 Chemical Properties

Melting point:

204 - 207°C

Boiling point:

694.3±65.0 °C(Predicted)

Density 

1.248

storage temp. 

-20°C

solubility 

Soluble in DMSO (up to 30 mg/ml)

form 

Yellow powder.

pka

14.20±0.10(Predicted)

color 

Yellow

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.

Safety Information

Safety Statements 

24/25

HS Code 

29335990

AZD-8055 Usage And Synthesis

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)

storage

Store at -20°C

References

[1] CHRISTINE M CHRESTA. AZD8055 is a potent, selective, and orally bioavailable ATP-competitive mammalian target of rapamycin kinase inhibitor with in vitro and in vivo antitumor activity.[J]. Cancer research, 2010, 70 1: 288-298. DOI:10.1158/0008-5472.can-09-1751
[2] KURT G. PIKE . Optimization of potent and selective dual mTORC1 and mTORC2 inhibitors: The discovery of AZD8055 and AZD2014[J]. Bioorganic & Medicinal Chemistry Letters, 2013, 23 5: Pages 1212-1216. DOI:10.1016/j.bmcl.2013.01.019
[3] SARAH V HOLT. Enhanced apoptosis and tumor growth suppression elicited by combination of MEK (selumetinib) and mTOR kinase inhibitors (AZD8055).[J]. Cancer research, 2012: 1804-1813. DOI:10.1158/0008-5472.can-11-1780
[4] L WILLEMS. The dual mTORC1 and mTORC2 inhibitor AZD8055 has anti-tumor activity in acute myeloid leukemia[J]. Leukemia, 2011, 26 6: 1195-1202. DOI:10.1038/leu.2011.339
[5] SHAORU LI. The mTOR inhibitor AZD8055 inhibits proliferation and glycolysis in cervical cancer cells.[J]. Oncology Letters, 2013: 717-721. DOI:10.3892/ol.2012.1058
[6] QIANG LI . The dual mTORC1 and mTORC2 inhibitor AZD8055 inhibits head and neck squamous cell carcinoma cell growth in vivo and in vitro[J]. Biochemical and biophysical research communications, 2013, 440 4: Pages 701-706. DOI:10.1016/j.bbrc.2013.09.130
[7] MIN HU. AZD8055 induces cell death associated with autophagy and activation of AMPK in hepatocellular carcinoma.[J]. Oncology reports, 2014: 649-656. DOI:10.3892/or.2013.2890

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