AZD2014 化学構造
分子量: 462.54

品質と確認

カスタマーレビュー(10)

Quality Control & MSDS

製品情報

  • Compare mTOR Inhibitors
    mTOR阻害剤を比較
  • 研究分野

製品の説明

生物活性

情報 AZD2014は、潜在的抗新生物性活動による新しい二重mTORC1とmTORC2阻害剤です。
目標 mTOR
IC50 2.8 nM [1]
In vitro試験 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試験 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]
臨床試験 AZD2014 is now under Phase 1 clinical trial to assess the safety, tolerability, pharmacokinetics and preliminary efficacy in advanced solid malignancies.
特集

推薦された実験操作 (公開の文献だけ)

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

参考

化学情報

Download AZD2014 SDF
分子量 462.54
化学式

C25H30N6O3

CAS No. 1009298-59-2
保管 2年-20℃
6月-80℃in DMSO
別名
溶解度 (25°C) * In vitro DMSO 38 mg/mL (82.15 mM)
<1 mg/mL (<1 mM)
エタノール <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.
化学名 3-(2,4-bis((S)-3-methylmorpholino)pyrido[2,3-d]pyrimidin-7-yl)-N-methylbenzamide

研究分野

カスタマーレビュー (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(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.

Click to enlarge
Rating
Source Biochem Biophys Res Commun, 2014, 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.

Click to enlarge
Rating
Source Biochem Biophys Res Commun, 2014, 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/MAPKwas tested by Western blots using antibodies listed.

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Rating
Source Biochem Biophys Res Commun, 2014, 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 tovehicle group, oral administration of AZD-2014 (5 mg/kg, P.O.14 days) dramatically inhibited the growth of HT-29 xenografts.

Click to enlarge
Rating
Source Biochem Biophys Res Commun, 2014, 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 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.

Click to enlarge
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 2013, 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 2013, 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).

製品表彰状 (7)

技術サポート&よくある質問(FAQ)

顧客がするかもしれない質問に対する答えは、指示を取り扱っている阻害剤で見つかります。話題は、貯蔵液(阻害剤と特別な注意を細胞ベースの分析法と動物のために必要とする問題を保存することは実験します)を準備する方法を含みます。

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