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AZD2014 Chemical Structure
|Product name: AZD2014|
|Cat. No.: HY-15247|
AZD2014 is a novel mTOR inhibitor with IC50 of 2.8 nM; highly selective against multiple PI3K isoforms (α/β/γ/δ).
IC50 value: 2.8 nM
AZD2014 is an orally bioavailable inhibitor of the mammalian target of rapamycin (mTOR) with potential antineoplastic activity. mTOR kinase inhibitor AZD2014 inhibits the activity of mTOR, which may result in the induction of tumor cell apoptosis and a decrease in tumor cell proliferation. mTOR, a serine/threonine kinase that is upregulated in a variety of tumors, plays an important role downstream in the PI3K/Akt/mTOR signaling pathway.
|M.Wt||462.54||Storage||Please store the product under the recommended conditions in the Certificate of Analysis.|
|Solvent & Solubility||
in DMSO > 10 mM
|1 mg||5 mg||10 mg|
|1 mM||2.1620 mL||10.8099 mL||21.6198 mL|
|5 mM||0.4324 mL||2.1620 mL||4.3240 mL|
|10 mM||0.2162 mL||1.0810 mL||2.1620 mL|
|Product Name||Sponsor Only||Condition||Start Date||End Date||Phase||Last Change Date|
|AZD2014||Queen Mary University of London||Metastatic renal cancer||28-FEB-13||31-DEC-15||Phase 2||19-NOV-13|
|AstraZeneca plc||Advanced solid tumor||31-DEC-09||28-FEB-14||Phase 1||06-NOV-13|
|Daiichi Sankyo Inc||Advanced solid tumor||30-APR-12||30-APR-15||Phase 1||20-MAY-13|
|AstraZeneca plc||Metastatic breast cancer||31-MAY-12||30-NOV-13||Phase 1||24-NOV-13|
. Sylvie M. Guichard, Zoe Howard, Dan Heathcote, Mark Roth, Gareth Hughes, Jon Curwen, James Yates, Armelle Logie, Sarah Holt, Christine M. Chresta, Barry R. Davies, Karine Malagu, Marc Hummersone, Sarah L. Pass, Stephen Green, and Martin Pass.Abstract 917: AZD2014, a dual mTORC1 and mTORC2 inhibitor is differentiated from allosteric inhibitors of mTORC1 in ER+ breast cancer.Cancer Research: April 15, 2012; Volume 72, Issue 8, Supplement 1.
The mammalian target of rapamycin (mTOR) is a major sensor of nutrients and energy and is part of two multiprotein complexes mTORC1 and mTORC2. mTOR activation is widely reported in cancer and is associated with poor prognosis and resistance to standard of care treatment. Allosteric inhibitors of mTOR such as rapamycin partially inhibit mTORC1 and do not inhibit mTORC2. 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. In vitro, the potency of AZD2014 is 5-fold lower compared to AZD8055. However, AZD2014 has improved pharmacokinetics compared to AZD8055. 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. Overall, AZD2014 is a potent mTOR kinase inhibitor with an in vitro profile comparable to AZD8055 but with improved pharmacokinetic properties over AZD8055. AZD2014 is currently in phase 1 clinical trials.
AZD8055 is a novel ATP-competitive mTOR inhibitor with IC50 of 0.8 nM with excellent selectivity (～1,000-fold) against PI3K isoforms and ATM/DNA-PK.
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ETP-46464 is a cell-permeable quinoline-containing heterotricyclic compound that acts as a potent inhibitor against mTOR, ATR, DNA-PK, PI 3-K(alpha), and ATM (IC50= 0.6, 14, 36, 170, and 545 nM, respectively).
Everolimus (RAD001) is a mTOR inhibitor of FKBP12 with IC50 of 1.6-2.4 nM.
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GDC-0980 (RG7422) is a potent, class I PI3K inhibitor for PI3K(alpha)/(beta)/(delta)/(gamma) with IC50 of 5 nM/27 nM/7 nM/14 nM, respectively; also a mTOR inhibitor with Ki of 17 nM, and highly selective versus others PIKK family kinases.
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