- WYE-354
- GDC-0349
- LY 303511
- GDC-mTOR inhibitor
- Nordihydroguaiaretic acid
| AZD2014Novel mTOR inhibitor |
Sample solution is provided at 25 µL, 10mM.
Nature.2017 Jan 19;541(7637):417-420.
Nature.2018 Nov;563(7731):407-411.Nature.2018 Jun 13.Nature.2018 Jun 27.Nature.2018 Mar 29;555(7698):673-677.Nature.2017 Sep 7;549(7670):96-100.Nature.2016 Apr 21;532(7599):398-401.
Science.2016 Aug 5;353(6299)594-8Nat Nanotechnol.2017 Dec;12(12):1190-1198.Nature Biotechnology.2017 Jun;35(6):569-576Nat Med.2018 Sep 17.Cell.2018 Dec 21. pii: S0092-8674(18)31561-7.Cell.Available online 25 October 2018.Cell.2018 Sep 27. pii: S0092-8674(18)31183-8.Cell.2018 Jun 28;174(1):172-186.e21.Cell.2018 Feb 22;172(5):1007-1021.e17.Cell.2017 Nov 30;171(6):1284-1300.e21.Cell.2017 Aug 17. pii: S0092-8674(17)30869-3.Cell.2017 Jul 13;170(2):312-323Nat Med.2018 Jan 29.Nat Med.2017 Nov;23(11):1342-1351.Cell.2017 Apr 6;169(2):286-300.Cell.2015 Aug 27;162(5):987-1002.Cell.2015 Feb 12;160(4):729-44.Nature Medicine.2017 Apr;23(4):493-500.Cancer Cell.2018 May 14;33(5):905-921.e5.Cancer Cell.2018 Apr 9;33(4):752-769.e8.Cancer Cell.2018 Mar 12;33(3):401-416.e8.Cancer Cell.2017 Aug 14;32(2):253-267.e5.Nat Methods.2018 Jul;15(7):523-526.Cell Stem Cell.2018 May 3;22(5):769-778.e4.Cell Stem Cell.2017 Nov 20. pii: S1934-5909(17)30375-2.Quality Control & MSDS
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- Purity = 98.36%
- COA (Certificate Of Analysis)
- HPLC(Retest)
- MSDS (Material Safety Data Sheet)
- Datasheet
Chemical structure
| Description | AZD2014 is a novel inhibitor of mTOR with an IC50 value of 2.8 nM. | |||||
| Targets | mTOR | P-Akt (S473) | pS6 (S235/236) | |||
| IC50 | 2.8 nM | 80 nM | 200 nM | |||
| Cell experiment [1]: | |
Cell lines | HCCLM3, Huh-7, SMMC-7721 and HepG2 cells |
Preparation method | The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
Reacting condition | 10 nM ~ 20 mM; 72 hrs |
Applications | In 4 selected HCC cell lines, AZD2014 exhibited a more profound antiproliferative activity than Rapamycin, with the IC50 values of 101, 441, 141 and 600 nM, respectively. SMMC-7721 cells were resistant to Rapamycin (even at a high concentration of 20 μM), but were highly sensitive to AZD2014 (141 nM). |
References: [1]. Dramatic antitumor effects of the dual mTORC1 and mTORC2 inhibitor AZD2014 in hepatocellular carcinoma.Am J Cancer Res. 2014 Dec 15;5(1):125-39. eCollection 2015. | |
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| Cas No. | 1009298-59-2 | SDF | Download SDF |
| Synonyms | AZD 2014;AZD-2014 | ||
| Chemical Name | 3-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl]-N-methylbenzamide | ||
| Canonical SMILES | CC1COCCN1C2=NC(=NC3=C2C=CC(=N3)C4=CC(=CC=C4)C(=O)NC)N5CCOCC5C | ||
| Formula | C25H30N6O3 | M.Wt | 462.54 |
| Solubility | ≥23.15mg/mL in DMSO | Storage | Store at -20°C |
| Physical Appearance | A solid | Shipping Condition | Evaluation sample solution : ship with blue ice.All other available size:ship with RT , or blue ice upon request |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. | ||
AZD2014 is a novel, potent and highly selective dual inhibitor of the mammalian rapamycin (mTORC1 and mTORC2) with an IC50 value of 2.8 nM. It is an oral inhibitor and possesses potential antineoplastic activity.
AZD2014 enhanced susceptibility of glioblastoma stem-like cells (GSCs) to irradiation both in vitro and under orthotopic in vivo conditions. Kahn J et al pretreated CD133+ and CD15+ GSC cells with AZD2014 (2 µM) for 1 hour, followed by irradiation. The effect was then measured by clonogenic survival analysis [2]. Using in vitro screening, they demonstrated that the combination of ibrutinib, an inhibitor of the tyrosine kinase BTK, and AZD2014 could dramatically induce apoptosis in ABC-subtype DLBCL cell lines. Thereby, the combination of AZD2014 with a BTK inhibitor is a promising therapeutic method to cure patients with ABC-type DLBCL [3]. In hepatocellular carcinoma cells, AZD2014 gave rise to a more complete inhibition of mTORC1 than rapamycin, while the inhibition of mTORC2 prevented the feedback activation of AKT signaling. Therefore, AZD2014 was identified to be more efficacious in the induction of apoptosis, autophagy, and cell cycle arrest, resulting in a significant proliferation suppression of the cells, in contrast with rapamycin [4].
In a recent human pharmacokinetic and pharmacodynamic study, a dose of 50mg BD(twice a day)AZD2014 was recommended to achieve pharmacologically relevant plasma concentrations [5].
References:Optimization of potent and selective dual mTORC1 and mTORC2 inhibitors: the discovery of AZD8055 and AZD2014. Bioorg Med Chem Lett. 2013 Mar 1;23(5):1212-6. The mTORC1/mTORC2 inhibitor AZD2014 enhances the radiosensitivity of glioblastoma stem-like cells. Neuro Oncol. 2014 Jan;16(1):29-37. Synergistic induction of apoptosis by combination of BTK and dual mTORC1/2 inhibitors in diffuse large B cell lymphoma. Oncotarget. 2014 Jul 15;5(13):4990-5001.Dramatic antitumor effects of the dual mTORC1 and mTORC2 inhibitor AZD2014 in hepatocellular carcinoma. Am J Cancer Res. 2014 Dec 15;5(1):125-39. eCollection 2015.First-in-human pharmacokinetic and pharmacodynamic study of the dual m-TORC 1/2 inhibitor, AZD2014. Clin Cancer Res. 2015 Mar 24. pii: clincanres.2422.2014.
