"目录号: HY-13898
PI3K/Akt/mTOR-
GDC-0032 是一种有效的PI3K抑制剂，能够抑制 PI3Kα，PI3Kβ 和 PI3Kγ 的活性，IC50值分别为 0.29 nM，0.91 nM，0.97 nM。
PI3K
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生物活性
Description
GDC-0032 is a potent β-sparing small molecule inhibitor ofPI3K, withIC50values of 0.29 nM, 0.91 nM, 0.97 nM for PI3Kα, PI3Kβ and PI3Kγ, respectively.
IC50& Target
IC50: 0.29 nM (PI3Kα), 0.91 nM (PI3Kβ), 0.97 nM (PI3Kγ), 0.12 nM (PI3Kδ)
In Vitro
GDC-0032 (100 nM) inhibits AKT/mTOR signaling in PIK3CA mutant cell lines but not in cells with loss or mutation of PTEN; GDC-0032 enhances radiation-induced apoptosis and inhibits growth in head and neck cancer cell lines that are sensitive to its single-agent activiy[1]. GDC-0032 enhances the effects of MEK1/2 inhibition on both BRAFV600E/PTENNullhuman melanoma cells autochthonous mouse melanomas[2].
In Vivo
GDC-0032 (5 mg/kg, p.o.) potently impairs PI3K signaling and enhances the efficacy of fractionated radiotherapy; GDC-0032 and radiation is more effective than either treatment alone in nude mice implanted with subcutaneous Cal-33 xenografts[1]. The vehicle-treated BRAFV600E/PTENNull melanoma-bearing mice experiencs initial tumor regression after treatment with GDC-0032 (22.5 mg/kg, p.o.)[2].
Clinical Trial
NCT02285179
The Netherlands Cancer Institute-Genentech, Inc.-EurocanPlatform-Rather
Breast Cancer-Ovarian Cancer-Cancer of the Uterus
November 2014
Phase 1
NCT01814709
Genentech, Inc.
Healthy Volunteer
April 2013
Phase 1
NCT01967966
Genentech, Inc.
Healthy Volunteer
November 2013
Phase 1
NCT01980953
Genentech, Inc.
Healthy Volunteer
November 2013
Phase 1
NCT01296555
Genentech, Inc.
Solid Cancers-Non-Hodgkin's Lymphoma
March 16, 2011
Phase 1
NCT01862081
Genentech, Inc.
Breast Cancer, Non-small Lung Cancer
July 16, 2013
Phase 1
NCT02340221
Hoffmann-La Roche
Breast Cancer
April 9, 2015
Phase 3
NCT02785913
Southwest Oncology Group-National Cancer Institute (NCI)
Recurrent Squamous Cell Lung Carcinoma-Stage IV Squamous Cell Lung Carcinoma
June 2014
Phase 2
NCT02457910
Vanderbilt-Ingram Cancer Center-National Cancer Institute (NCI)-Translational Breast Cancer Research Consortium-Conquer Cancer Foundation-Genentech, Inc.
Estrogen Receptor Negative-Estrogen Receptor Positive-HER2/Neu Negative-Progesterone Receptor Negative-Progesterone Receptor Positive-Stage IV Breast Cancer-Triple-Negative Breast Carcinoma
June 2015
Phase 1-Phase 2
NCT02390427
Dana-Farber Cancer Institute-Genentech, Inc.
Metastatic Breast Cancer-Recurrent Breast Cancer
April 2015
Phase 1
NCT02273973
Genentech, Inc.-SOLTI Breast Cancer Research Group-Breast International Group-Austrian Breast and Colorectal Cancer Group
Breast Cancer
November 12, 2014
Phase 2
NCT02389842
Royal Marsden NHS Foundation Trust-Institute of Cancer Research, United Kingdom-Roche Pharma AG-Pfizer
Advanced Solid Tumours-Breast Cancer
February 2015
Phase 1
NCT02154490
Southwest Oncology Group-National Cancer Institute (NCI)
Recurrent Squamous Cell Lung Carcinoma-Stage IV Squamous Cell Lung Carcinoma
June 2014
Phase 2-Phase 3
NCT02465060
National Cancer Institute (NCI)
Advanced Malignant Solid Neoplasm-Bladder Carcinoma-Breast Carcinoma-Cervical Carcinoma-Colon Carcinoma-Colorectal Carcinoma-Endometrial Carcinoma-Esophageal Carcinoma-Gastric Carcinoma-Glioma-Head and Neck Carcinoma-Kidney Carcinoma-Liver and Intrahepatic Bile Duct Carcinoma-Lung Carcinoma-Lymphoma-Malignant Uterine Neoplasm-Melanoma-Ovarian Carcinoma-Pancreatic Carcinoma-Plasma Cell Myeloma-Prostate Carcinoma-Rectal Carcinoma-Recurrent Bladder Carcinoma-Recurrent Breast Carcinoma-Recurrent Cer
August 12, 2015
Phase 2
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References
[1].Zachary S. Zumsteg, et al. Taselisib (GDC-0032), a Potent β-Sparing Small Molecule Inhibitor of PI3K, Radiosensitizes Head and Neck Squamous Carcinomas Containing Activating PIK3CA Alterations. Clin Cancer Res. 2016 Apr 15; 22(8): 2009–2019.
[2].Marian M. Deuker, et al. PI3′-Kinase Inhibition Forestalls the Onset of MEK1/2 Inhibitor Resistance in BRAF-Mutated Melanoma. Cancer Discov. 2015 Feb; 5(2): 143–153.
[3].Cocco E, et al. Dual CCNE1/PIK3CA targeting is synergistic in CCNE1-amplified/PIK3CA-mutated uterine serous carcinomas in vitro and in vivo. Br J Cancer. 2016 Jul 26;115(3):303-11.