>>Signaling Pathways>> Ubiquitination/ Proteasome>> Autophagy>>AZD8055

AZD8055 (Synonyms: CCG-168)

Catalog No.GC16380

MTOR 억제제

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AZD8055 Chemical Structure

Cas No.: 1009298-09-2

Size 가격 재고 수량
10mM (in 1mL DMSO)
US$41.00
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10mg
US$37.00
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50mg
US$83.00
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100mg
US$133.00
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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

Cell experiment: [1]

Cell lines

TamR and MCF7-X 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.

Reaction Conditions

100 nM, 3 days

Applications

The impact of AZD8055 on TamR and MCF-7-X cell proliferation was monitored using MIB1 Ki67 staining. Three days treatment with 50 nM AZD8055 reduced Ki67 staining in both TamR and MCF7-X cells and after treatment with 100 nM 40% to 50% of all cells were deemed negative for MIB1 indicating a significant exit from the cell cycle.

Animal experiment: [2]

Animal models

Female C57BL/6 mice

Dosage form

Intraperitoneal injection, 10 mg/kg

Applications

Overnight fasted mice were intraperitoneal-injected with either vehicle or AZD8055. 3 h after AZD8055 injection additional blood was sampled for plasma insulin and fatty acids (FA) determinations. Glucose levels in AZD8055 injected mice were elevated 3 and 6 h after drug injection but were similar to control mice at 24 h after drug injection. Along with elevated glucose levels at 3 h, AZD8055 treated mice had 3-fold higher plasma insulin levels and lower plasma FAs.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1] Jordan NJ, Dutkowski CM, Barrow D, Mottram HJ, Hutcheson IR, Nicholson RI, Guichard SM, Gee JM. Impact of dual mTORC1/2 mTOR kinase inhibitor AZD8055 on acquired endocrine resistance in breast cancer in vitro. Breast Cancer Res. 2014 Jan 23;16(1):R12.

[2] Kleinert M, Sylow L, Fazakerley DJ, Krycer JR, Thomas KC, Oxbøll AJ, Jordy AB, Jensen TE, Yang G, Schjerling P, Kiens B, James DE, Ruegg MA, Richter EA. Acute mTOR inhibition induces insulin resistance and alters substrate utilization in vivo. Mol Metab. 2014 Jun 27;3(6):630-41.

Background

AZD8055은 mTOR 키나아제의 선택적 억제제로, IC50 값은 0.8 nM입니다 [1]. 이는 mTOR의 ATP 결합 클레프트에서 ATP와 경쟁합니다. AZD8055은 PI3K 아이소폼과 ATM/DNA-PK와 밀접한 관련성을 가진 키나아제에 대해 약 1000 배의 선택성을 보였습니다 [1]. 또한, 10 μM에서 260 개의 키나아제 패널에서 유의미한 활동을 나타내지 않았습니다 [1]. AZD8055는 선행 연구에서 잠재적인 항암 활동을 보여주었습니다. mTOR는 전사 인자를 인산화하고 활성화시켜서 세포 성장, 증식, 운동 및 생존을 조절합니다. AZD8055는 mTORC1 및 mTORC2 복합체의 하류 신호전달도 억제하였으며[1], 폐암, 자궁경부암 및 후두암 등 다양한 악성 종양 줄기세포계열에서 세포 증식 억제 작용을 나타내었습니다[1-4]. Xenograft 모델 실험 결과, AZD8055는 뇌종양, 유방암, 폐암, 대장암, 전립선암, 자궁내막암 및 머리와 목의 악성 종양 성장을 억제하는 것으로 나타났습니다[1, 5]. 게다가 AZD8055는 HDAC 억제제 및 MEK 억제제의 효능을 증대시켰습니다 [6-8]. AZD8055은 제1상 임상시험에서 최소한의 임상적 이점만 보였습니다 [9, 10].

References:

[1]Chresta CM, Davies BR, Hickson I et al. 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 2010; 70: 288-298.
[2]Li S, Li Y, Hu R et al. The mTOR inhibitor AZD8055 inhibits proliferation and glycolysis in cervical cancer cells. Oncol Lett 2013; 5: 717-721.
[3]Willems L, Chapuis N, Puissant A et al. The dual mTORC1 and mTORC2 inhibitor AZD8055 has anti-tumor activity in acute myeloid leukemia. Leukemia 2012; 26: 1195-1202.
[4]Zhao L, Teng B, Wen L et al. mTOR inhibitor AZD8055 inhibits proliferation and induces apoptosis in laryngeal carcinoma. Int J Clin Exp Med 2014; 7: 337-347.
[5]Li Q, Song XM, Ji YY et al. 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 2013; 440: 701-706.
[6]Shao H, Gao C, Tang H et al. Dual targeting of mTORC1/C2 complexes enhances histone deacetylase inhibitor-mediated anti-tumor efficacy in primary HCC cancer in vitro and in vivo. J Hepatol 2012; 56: 176-183.
[7]Holt SV, Logie A, Davies BR et al. Enhanced apoptosis and tumor growth suppression elicited by combination of MEK (selumetinib) and mTOR kinase inhibitors (AZD8055). Cancer Res 2012; 72: 1804-1813.
[8]Renshaw J, Taylor KR, Bishop R et al. Dual blockade of the PI3K/AKT/mTOR (AZD8055) and RAS/MEK/ERK (AZD6244) pathways synergistically inhibits rhabdomyosarcoma cell growth in vitro and in vivo. Clin Cancer Res 2013; 19: 5940-5951.
[9]Asahina H, Nokihara H, Yamamoto N et al. Safety and tolerability of AZD8055 in Japanese patients with advanced solid tumors; a dose-finding phase I study. Invest New Drugs 2013; 31: 677-684.
[10]Naing A, Aghajanian C, Raymond E et al. Safety, tolerability, pharmacokinetics and pharmacodynamics of AZD8055 in advanced solid tumours and lymphoma. Br J Cancer 2012; 107: 1093-1099.

Chemical Properties

Cas No. 1009298-09-2 SDF
Synonyms CCG-168
Chemical Name [5-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl]-2-methoxyphenyl]methanol
Canonical SMILES CC1COCCN1C2=NC(=NC3=C2C=CC(=N3)C4=CC(=C(C=C4)OC)CO)N5CCOCC5C
Formula C25H31N5O4 M.Wt 465.54
Solubility ≥ 23.3mg/mL in DMSO Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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1 mg 5 mg 10 mg
1 mM 2.148 mL 10.7402 mL 21.4804 mL
5 mM 0.4296 mL 2.148 mL 4.2961 mL
10 mM 0.2148 mL 1.074 mL 2.148 mL
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Average Rating: 5 ★★★★★ (Based on Reviews and 18 reference(s) in Google Scholar.)

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