"目录号: HY-13956
Cell Cycle/DNA DamageNF-κB-
Pioglitazone (U 72107)是选择性PPARγ刺激剂。
PPAR
相关产品
GW9662-Rosiglitazone-Retinoic acid-Troglitazone-Pioglitazone hydrochloride-Elafibranor-GW 501516-CDDO-Im-Fenofibrate-T0070907-Wy-14643-GW0742-Daidzein-FH535-BMS-687453-
生物活性
Description
Pioglitazone (U 72107) is a selective peroxisome proliferator-activated receptor gamma(PPARγ) stimulator.IC50 Value:Target: PPARin vitro: HIT-T15 cells were cultured for 5 days in the presence of AGEs alone, or supplemented with 1 μmol/l Pioglitazone. Cell viability, insulin secretion and insulin content, redox balance, expression of the AGE receptor (RAGE), and NF-kB activation were then determined. The results showed that Pioglitazone protected beta cellsagainst AGEs-induced apoptosis and necrosis. Moreover, Pioglitazone restored the redox balance and improved the responsiveness to low glucose concentration. Adding Pioglitazone to the AGEs culture attenuated NF-kB phosphorylation, and prevented AGEs to down-regulate IkBα expression [1]. Pioglitazone attenuated AngII-induced CTGF expression and proliferation in atrial fibroblasts, and pioglitazone also inhibited the expression or phosphorylation of AngII-induced transforming growth factor-β1 (TGF-β1), tumor necrosis factor receptor associated factor 6 (TRAF6), TGF-β-associated kinase 1 (TAK1) and Smad2/3. In HL-1 cells, pioglitazone suppressed AngII-induced ICa-L α1c expression and current density as well as CAMP responsive element binding protein (CREB) phosphorylation. Besides, pioglitazone inhibited AngII-induced production of AngII type I receptor (AT1R) and downregulation of PPAR-γ in both atrial fibroblasts and HL-1 cells. In conclusion, Pioglitazone suppresses AngII-induced CTGF expression and proliferation in atrial fibroblasts, which might be at least in part related with its inhibitory effects on TGF-β1/Smad2/3 and TGF-β1/TRAF6/TAK1 signaling pathways [2]. in vivo: Diabetic nephropathic group treated by oral administration of pioglitazone (10 mg/kg per d) for 4 weeks. DN (Diabetic nephropathic) rats showed excessive deposition of collagen fibers in their cardiac tissue, along with a marked myocyte hypertrophy. This was associated with a dramatic upregulation of cardiac transforming growth factor-β1 (TGF-β1) gene. Furthermore, the gene expression of matrix metalloproteinase 2 (MMP-2) decreased, while the gene expression of tissue inhibitor of metalloproteinase 2 (TIMP-2) increased in the hearts of DN rats [3]. Pioglitazone, given orally at a dose of 2.5mg/kg/d, reduced cardiac triglyceride content and suppressed lipid deposition in the heart of angiotensin II-induced hypertensive rats without affecting angiotensin II-induced upregulation of lipogenic gene expression [4]. Toxicity: On June 9, 2011 the French Agency for the Safety of Health Products decided to withdraw pioglitazone in regards to high risk of bladder cancer.
Clinical Trial
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Children's Hospital of Fudan University
Chronic Granulomatous Disease
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University Hospital, Geneva-University of Lausanne Hospitals
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Indiana University
Polycystic Kidney Disease
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Paul Beringer-University of Southern California
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Wake Forest University Health Sciences
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Children's Hospital Medical Center, Cincinnati
Severe Sepsis-Septic Shock
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Takeda-Kaiser Permanente-Department of Epidemiology at University of Pennsylvania
Diabetes-Bladder Cancer
July 2004
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Assistance Publique - Hôpitaux de Paris
Friedreich's Ataxia
December 2008
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Mild Cognitive Impairment Due to Alzheimer's Disease
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Hepatitis
April 2009
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Takeda
Diabetes Mellitus, Type 2, Cancer
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King Abdulaziz University
Diabetes Mellitus-Diabetes Mellitus, Type 2-Glucose Metabolism Disorders
January 2009
Phase 2
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University Hospitals Cleveland Medical Center-National Alliance for Research on Schizophrenia and Depression-Takeda Pharmaceuticals North America, Inc.
Metabolic Syndrome-Bipolar Depression-Insulin Resistance
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Phase 4
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The University of Texas Health Science Center at San Antonio
Type 2 Diabetes-Healthy-Impaired Glucose Tolerance
June 2007
Phase 4
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Takeda
Type II Diabetes Mellitus
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Phase 4
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Pusan National University Hospital
Type 2 Diabetes
December 2009
Phase 4
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Dana-Farber Cancer Institute
Advanced Solid Tumor-Metastatic Solid Tumor
August 2011
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LG Life Sciences
Healthy
February 2009
Phase 1
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University of Texas Southwestern Medical Center-National Institutes of Health (NIH)
Obesity-Type 2 Diabetes
February 2009
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Huashan Hospital-Baxter Healthcare Corporation
Peritoneal Dialysis-Pioglitazone-Hypertriglyceridemia-Insulin Resistance-Inflammation
January 2008
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University of Rochester
Diabetes-Platelet Function-Healthy
December 2008
Phase 2
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The University of Texas Health Science Center at San Antonio
Type 2 Diabetes
August 2009
Phase 4
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Stanford University
Cardiac Allograft Vasculopathy
July 2010
Phase 2
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Takeda
Mild Cognitive Impairment Due to Alzheimer's Disease
November 17, 2014
Phase 3
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Emory University-National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Alcoholism
August 28, 2017
Phase 2
NCT01935466
Postgraduate Institute of Medical Education and Research
Bladder Cancer
July 2013
NCT01819402
Kurume University
To Evaluate the Effect of Pioglitazone on Glucose Metabolism of Fat Tissue by Using FDG-PET/CT Imaging
March 2012
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Dana King-Takeda Pharmaceuticals North America, Inc.-Medical University of South Carolina
Diabetes
October 2008
Phase 4
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Emory University
Chronic Myelogenous Leukemia, BCR-ABL1 Positive-Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive
May 2016
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National Cancer Institute (NCI)
Head and Neck Cancer-Oral Leukoplakia
June 2003
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Coordinación de Investigación en Salud, Mexico
Type 2 Diabetes
October 2005
Phase 1-Phase 2
NCT02181842
Takeda
Type 2 Diabetes Mellitus
January 2009
NCT01156597
University of Miami-Takeda Pharmaceuticals North America, Inc.
Type 2 Diabetes Mellitus
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Phase 3
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University of Rochester-National Institute of Neurological Disorders and Stroke (NINDS)-Michael J. Fox Foundation for Parkinson's Research
Parkinson's Disease
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University of Michigan-National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Chronic Pancreatitis-Insulin Resistance-Normal Stool Fat Levels
November 2008
Phase 2
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University of Dhaka-Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders-University of Dundee
Type 2 Diabetes Mellitus
November 2008
Phase 4
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Skane University Hospital-Medical Research Council-Skane County Council Research & Development Foundation
Type 2 Diabetes-Secondary Drug Failure
April 2004
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Stony Brook University
Type 1 Diabetes Mellitus
June 2002
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AstraZeneca
Type 2 Diabetes Mellitus
February 2010
Phase 1
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Takeda
Diabetes Mellitus
December 2002
Phase 2
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Takeda-Eli Lilly and Company
Diabetes Mellitus
May 2001
Phase 3
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Sung-Chen Liu-Mackay Memorial Hospital
Type 2 Diabetes
October 2009