"目录号: HY-15247
AZD2014 是一种ATP竞争性的mTOR抑制剂，IC50为 2.81 nM。
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生物活性
Description
AZD2014 is an ATP competitivemTORinhibitor withIC50of 2.81 nM.
IC50& Target
IC50: 2.81 nM (mTOR)[1]
In Vitro
The inhibitory effects of AZD2014 are measured against isolated recombinant mTOR enzyme (IC50of 2.81 nM) as well as in cellular assays measuring both mTORC1 and mTORC2 activities. In MDAMB468 cells, AZD2014 decreases the phosphorylation of the mTORC1 substrate ribosomal protein S6 (Ser235/236) with a mean IC50value of 210 nM and the mTORC2 substrate AKT (Ser473) with a mean IC50value of 78 nM[1].
In Vivo
AZD2014 induces dose-dependent tumor growth inhibition in several xenograft and primary explant models. The antitumor activity of AZD2014 is associated with modulation of both mTORC1 and mTORC2 substrates, consistent with its mechanism of action. The pharmacokinetics of AZD2014 in mice is tested upon administration of doses between 7.5 and 15 mg/kg. A dose-dependent increase in Cmaxand AUC is observed following single dose and repeat dosing of AZD2014: Cmaxrange from 1 to 16 μM and AUC range from 220 to 5,042 μM·h across this dose range. The pharmacodynamic effect of AZD2014 against an mTORC1 biomarker (phosphorylation of S6) and an mTORC2 biomarker (phosphorylation of AKT) is assessed in SCID mice bearing MCF7 xenografts following administration of 3.75, 7.5, and 15 mg/kg AZD2014. There is a good relationship between the drug plasma concentrations and biomarker levels (estimated p-AKT IC50of 0.119 μM total, 53% SE, and estimated p-S6 IC500.392 μM, 28.8% SE)[1].
Clinical Trial
Samsung Medical Center
Stomach Neoplasms
February 1, 2017
Phase 2
Royal Marsden NHS Foundation Trust-Institute of Cancer Research, United Kingdom-AstraZeneca
Advanced Cancer
April 2013
Phase 1
Samsung Medical Center
Solid Tumor
July 2017
Phase 2
Cambridge University Hospitals NHS Foundation Trust-AstraZeneca
Prostate Cancer
October 2014
Phase 1
AstraZeneca
Advanced Metastatic Breast Cancer
May 8, 2012
Phase 1
Canadian Cancer Trials Group-AstraZeneca
Glioblastoma Multiforme
November 2015
Phase 1-Phase 2
AstraZeneca
Core: Relapsed or Refractory Diffuse Large B-Cell Lymphoma-Module 1: Non-GCB Diffuse Large B-Cell Lymphoma
June 2016
Phase 1
AstraZeneca
Advanced Solid Malignancies
December 2009
Phase 1
Queen Mary University of London-AstraZeneca-Cancer Research UK
Metastatic Clear Cell Renal Carcinoma
February 2013
Phase 2
Massachusetts General Hospital-National Cancer Institute (NCI)-AstraZeneca
Meningioma
April 15, 2017
Phase 2
M.D. Anderson Cancer Center-AstraZeneca-National Cancer Institute (NCI)
Breast Cancer-Malignant Female Reproductive System Neoplasm
November 2014
Phase 1-Phase 2
Massachusetts General Hospital-AstraZeneca-United States Department of Defense
Neurofibromatosis 2-Meningioma
July 2016
Phase 2
Queen Mary University of London-Cancer Research UK-AstraZeneca
Triple-Negative Breast Cancer-Squamous Cell Lung Cancer-Non-squamous Cell Lung Cancer With KRAS Mutations-Non-squamous Cell Lung Cancer With Wild-type KRAS
June 2015
Phase 1-Phase 2
AstraZeneca
Squamous Non Small Cell Lung Cancer
April 2015
Phase 2
AstraZeneca
Advanced Solid Malignancies
March 17, 2015
Phase 1
Samsung Medical Center-AstraZeneca
Small Cell Lung Cancer
August 2017
Phase 2
Samsung Medical Center
Cancer of Stomach
February 1, 2017
Phase 2
Samsung Medical Center
Solid Tumor
July 2017
Phase 2
AstraZeneca-SCRI Development Innovations, LLC
Advanced and Metastatic Breast Cancer
December 7, 2015
Phase 1-Phase 2
AstraZeneca-Quintiles, Inc.
Solid Malignancies
January 28, 2016
Phase 1
Queen Mary University of London-AstraZeneca
Estrogen Receptor Positive Breast Cancer
January 2014
Phase 2
Centre Leon Berard
Endometrial Carcinoma-Metastatic Carcinoma-Hormone Receptor Positive Tumor
April 2016
Phase 1-Phase 2
Samsung Medical Center
Advanced Gastric Adenocarcinoma
February 12, 2015
Phase 2
AstraZeneca
Advanced Castrate-resistant Prostate Cancer CRPC-Squamous Non-Small Cell Lung Cancer sqNSCLC-Triple Negative Breast Cancer TNBC
July 9, 2013
Phase 1
Joseph Paul Eder-Dana-Farber Cancer Institute-Vanderbilt-Ingram Cancer Center-Yale University
Cancer
November 2015
Phase 2
University of Birmingham-Cancer Research UK-AstraZeneca-Pfizer-Experimental Cancer Medicine Centre Network
Non-Small Cell Lung Cancer-Carcinoma, Squamous Cell-Adenocarcinoma
March 2015
Phase 2
UNICANCER-IFCT-Fondation ARC-AstraZeneca
Non-small Cell Lung Cancer Metastatic
April 23, 2014
Phase 2
UNICANCER-Fondation ARC-AstraZeneca
Metastatic Breast Cancer
April 7, 2014
Phase 2
Gustave Roussy, Cancer Campus, Grand Paris-National Cancer Institute, France
Children, Adolescents and Young Adults With Refractory or Recurrent Malignancies
June 2016
Phase 1-Phase 2
Samsung Medical Center
Stomach Neoplasms
February 1, 2017
Phase 2
Royal Marsden NHS Foundation Trust-Institute of Cancer Research, United Kingdom-AstraZeneca
Advanced Cancer
April 2013
Phase 1
Samsung Medical Center
Solid Tumor
July 2017
Phase 2
Cambridge University Hospitals NHS Foundation Trust-AstraZeneca
Prostate Cancer
October 2014
Phase 1
AstraZeneca
Advanced Metastatic Breast Cancer
May 8, 2012
Phase 1
Canadian Cancer Trials Group-AstraZeneca
Glioblastoma Multiforme
November 2015
Phase 1-Phase 2
AstraZeneca
Core: Relapsed or Refractory Diffuse Large B-Cell Lymphoma-Module 1: Non-GCB Diffuse Large B-Cell Lymphoma
June 2016
Phase 1
AstraZeneca
Advanced Solid Malignancies
December 2009
Phase 1
Queen Mary University of London-AstraZeneca-Cancer Research UK
Metastatic Clear Cell Renal Carcinoma
February 2013
Phase 2
Massachusetts General Hospital-National Cancer Institute (NCI)-AstraZeneca
Meningioma
April 15, 2017
Phase 2
M.D. Anderson Cancer Center-AstraZeneca-National Cancer Institute (NCI)
Breast Cancer-Malignant Female Reproductive System Neoplasm
November 2014
Phase 1-Phase 2
Massachusetts General Hospital-AstraZeneca-United States Department of Defense
Neurofibromatosis 2-Meningioma
July 2016
Phase 2
Queen Mary University of London-Cancer Research UK-AstraZeneca
Triple-Negative Breast Cancer-Squamous Cell Lung Cancer-Non-squamous Cell Lung Cancer With KRAS Mutations-Non-squamous Cell Lung Cancer With Wild-type KRAS
June 2015
Phase 1-Phase 2
AstraZeneca
Squamous Non Small Cell Lung Cancer
April 2015
Phase 2
AstraZeneca
Advanced Solid Malignancies
March 17, 2015
Phase 1
Samsung Medical Center-AstraZeneca
Small Cell Lung Cancer
August 2017
Phase 2
