AZD2014

Catalog No.S2783
5 5 6 Product Citations

AZD2014 is a novel mTOR inhibitor with IC50 of 2.8 nM; highly selective against multiple PI3K isoforms (α/β/γ/δ). Phase 2.

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AZD2014 Chemical Structure

AZD2014 Chemical Structure
Molecular Weight: 462.54

Validation & Quality Control

Customer Reviews(10)

Quality Control & MSDS

Related Compound Libraries

AZD2014 is available in the following compound libraries:

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Product Information

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  • Research Area
  • Inhibition Profile

Product Description

Biological Activity

Description AZD2014 is a novel mTOR inhibitor with IC50 of 2.8 nM; highly selective against multiple PI3K isoforms (α/β/γ/δ). Phase 2.
Targets mTOR [1] P-Akt (S473) [1] pS6 (S235/236) [1]
IC50 2.8 nM 80 nM 200 nM
In vitro AZD2014 is a close analogue of AZD8055 and a selective inhibitor of mTOR kinase. AZD2014 has greater inhibitory activity against mTORC1 compared to rapamycin: AZD2014 decreases p4EBP1 Thr37/46, inhibits the translation initiation complex and decreases overall protein synthesis while rapamycin has no effect. AZD2014 also inhibits the mTORC2 biomarkers pAKTSer473 and pNDRG1Thr346. AZD2014 has broad antiproliferative activity across multiple tumour cell lines. In particular, AZD2014 induces growth inhibition and cell death in breast cancer cell lines, including ER+ cell lines with acquired resistance to hormone therapy. [1]
In vivo AZD2014 induces tumour growth inhibition against several xenograft models including a human primary explant model of ER+ breast cancer refractory to tamoxifen. The antitumour activity is associated with modulation of both mTORC1 and mTORC2 substrates. [1]
Features

Protocol(Only for Reference)

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesBaboonDogMonkeyRabbitGuinea pigRatHamsterMouse
Weight (kg)121031.80.40.150.080.02
Body Surface Area (m2)0.60.50.240.150.050.0250.020.007
Km factor202012128653
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Sylvie M, et al, AACR Annual Meeting, 2012, Abst 917.

Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2014-11-22)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT02208375 Recruiting Breast Cancer|Malignant Female Reproductive System Neoplasm M.D. Anderson Cancer Center|AstraZeneca November 2014 Phase 1|Phase 2
NCT02064608 Not yet recruiting Prostate Cancer Cambridge University Hospitals NHS Foundation Trust|Astra  ...more Cambridge University Hospitals NHS Foundation Trust|AstraZeneca June 2014 Phase 1
NCT02117167 Recruiting Non-small Cell Lung Cancer Metastatic UNICANCER|IFCT|Fondation ARC|AstraZeneca April 2014 Phase 2
NCT02216786 Recruiting Estrogen Receptor Positive Breast Cancer Queen Mary University of London|AstraZeneca January 2014 Phase 2
NCT02193633 Recruiting Advanced Cancer Royal Marsden NHS Foundation Trust|Institute of Cancer Re  ...more Royal Marsden NHS Foundation Trust|Institute of Cancer Research, United Kingdom|AstraZeneca April 2013 Phase 1

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Chemical Information

Download AZD2014 SDF
Molecular Weight (MW) 462.54
Formula

C25H30N6O3

CAS No. 1009298-59-2
Storage 3 years -20℃Powder
6 months-80℃in DMSO
Synonyms
Solubility (25°C) * In vitro DMSO 38 mg/mL (82.15 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo 30% PEG400/0.5% Tween80/5% propylene glycol 30 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name 3-(2,4-bis((S)-3-methylmorpholino)pyrido[2,3-d]pyrimidin-7-yl)-N-methylbenzamide

Research Area

Customer Reviews (10)


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Rating
Source J Biol Chem 2013 288(47), 33966-77. AZD2014 purchased from Selleck
Method Immunoblot analysis
Cell Lines Murine macrophages cells
Concentrations 10 nM
Incubation Time 0-180 min
Results AZD2014 is a newer second generation mTOR inhibitor that inhibits both TORC1 and TORC2. It's tested whether AZD2014 similarly activates the ERK and the AKT pathways and enhances MKP-1 expression. AZD2014 treatment evoked a delayed ERK phosphorylation (B) and resulted in a delayed MKP-1induction (C).

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Rating
Source Biochem Biophys Res Commun 2014 443, 406-12. AZD2014 purchased from Selleck
Method FACS
Cell Lines HT-29 cells
Concentrations 50 nM
Incubation Time 72 h
Results HT-29 cells were treated with vehicle or AZD-2014 (50 nM) for 72 h, cell cycle distribution was analyzed by FACS. AZD-2014 could arrest cells in G2 and G0/G1 phases.

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Rating
Source Biochem Biophys Res Commun 2014 443, 406-12. AZD2014 purchased from Selleck
Method MTT
Cell Lines HT-29 cells
Concentrations 1-100 nM
Incubation Time 72 h
Results HT-29 cells were treated with vehicle ("Ctrl") or different concentrations of AZD-2014 for 72 h. AZD-2014 dose-dependently inhibited HT-29 cell growth.

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Rating
Source Biochem Biophys Res Commun. 2014 Jan 10;443(2):406-12. AZD2014 purchased from Selleck
Method Western blot
Cell Lines SCID mice
Concentrations 5 mg/kg
Incubation Time 14 days
Results In tumors administrated with AZD-2014, the activation of mTORC1 (p-S6K and p-S6) and mTORC2 (p-Akt Ser 473) was both inhibited, which was showed by Western blot.

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Rating
Source Biochem Biophys Res Commun. 2014 Jan 10;443(2):406-12. AZD2014 purchased from Selleck
Method Western blot
Cell Lines SCID mice
Concentrations 5 mg/kg
Incubation Time 14 days
Results Autophagy was also induced in AZD-2014-treated tumors, as the expressions of LC3B-II and Beclin-1 were significantly upregulated.

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Rating
Source Biochem Biophys Res Commun. 2014 Jan 10;443(2):406-12. AZD2014 purchased from Selleck
Method Western blot
Cell Lines HT-29 and DLD-1 cells
Concentrations 25/50 nM
Incubation Time 12 h
Results HT-29 and DLD-1 cells were treated with vehicle or AZD-2014 (25/50 nM) for 12 h, activation of Akt, mTORC1/2 and Erk/MAPK was tested by Western blots using antibodies listed.

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Rating
Source Biochem Biophys Res Commun. 2014 Jan 10;443(2):406-12. AZD2014 purchased from Selleck
Method Tumor volume calculation
Cell Lines SCID mice
Concentrations 5 mg/kg
Incubation Time 14 days
Results As compared to vehicle group, oral administration of AZD-2014 (5 mg/kg, P.O.14 days) dramatically inhibited the growth of HT-29 xenografts .

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Rating
Source Biochem Biophys Res Commun. 2014 Jan 10;443(2):406-12. AZD2014 purchased from Selleck
Method
Cell Lines SCID mice
Concentrations 5 mg/kg
Incubation Time 14 days
Results The mice survival was dramatically improved with AZD-2014 administration.

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Rating
Source Dr. Milica Pesic from Institute for Biological Research. AZD2014 purchased from Selleck
Method Western blot
Cell Lines NCI-H460 cells /NCI-H460/R cells
Concentrations 100/250 nM
Incubation Time 18 h
Results Concentration-dependent cell growth inhibition induced by AZD2014 did not differ between sensitive (NCI-H460) and multi-drug resistant (NCI-H460/R) human non-small cell lung carcinoma cell lines (A). AZD2014 cell growth inhibition efficacy decreased in multi-drug resistant colorectal carcinoma cell line DLD1-TxR in comparison to its sensitive counterpart DLD1 (B). The results were obtained by the Sulforhodamine B assay. All values represent average ?SD obtained from two independent experiments, n = 5. (DLD1 possesses mutated p53, while its resistant counterpart DLD1-TxR additionally acquired the LOH in PTEN gene during the course of resistance induction.)

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Rating
Source Dr. Milica Pesic from Institute for Biological Research. AZD2014 purchased from Selleck
Method
Cell Lines Sea urchin embryo
Concentrations
Incubation Time 24 h
Results The effects of SelleckChem inhibitors on sea urchin embryo development evaluated 24 h after fertilization. All compounds were added to embryos suspension 20 min after fertilization. The relative presence of late gastrula, swimming blastula, undeveloped embryos and dead embryos was compared next to untreated control embryos (A). Fertilized egg, swimming blastula and late gastrula are illustrated (B). The embryonic development was relatively synchronized in untreated control samples after 24 h (A, E). GSK690693 treatment sustained the development of embryos. Swimming blastulas kept normal motility regardless the deformities in their shape. Tipifarnib treatment induced significant toxicity due to occurrence of dead fragmented embryos. Some abnormal blastulas kept the motility. AZD2014 treatment sustained the development of embryos. Some developed gastrulas and blastulas were less motile in comparison with control (A, C). WZ811 was the least toxic compound. Significant number of gastrulas and blastulas was developed. However, their motility was considerably suppressed (A, D). In contrast to SelleckChem inhibitors, classic anticancer agent – cisplatin was extremely toxic to sea urchin embryos (A). Cisplatin killed many embryos, while a small amount of survived embryos was stopped at early phases of development: immediately after fertilization or after first and second division (A, F).

Product Citations (6)

Tech Support & FAQs

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