伊格列扎(Imiglitazar) - 药物靶点：PPARα x PPARγ_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

PPARα x PPARγ

作用机制

PPARα激动剂(过氧化物酶体增长因子活化受体α激动剂)、PPARγ激动剂(过氧化物酶体增长因子活化受体γ激动剂)

治疗领域

内分泌与代谢疾病

在研适应症-

非在研适应症

2型糖尿病

原研机构

Takeda Pharmaceutical Co., Ltd.

在研机构-

非在研机构

Takeda Pharmaceutical Co., Ltd.

最高研发阶段终止临床3期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C28H26N2O5

InChIKeyULVDFHLHKNJICZ-QCWLDUFUSA-N

CAS号250601-04-8

关联

6

项与伊格列扎相关的临床试验

NCT00762684 / Terminated临床3期

A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Parallel Study of the Safety and Efficacy of TAK-559 Compared to Placebo in the Treatment of Patients With Type 2 Diabetes Mellitus

The purpose of this study was to determine the safety and efficacy of TAK-559, once daily (QD), in treating subjects with type 2 diabetes mellitus.

开始日期2004-11-01

申办/合作机构

Takeda Pharmaceutical Co., Ltd.

NCT00759720 / Terminated临床3期

A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Parallel Study of the Safety and Efficacy of a Combination of TAK-559 and Glyburide Compared to Placebo and Glyburide in the Treatment of Patients With Type 2 Diabetes Mellitus

The purpose of this study is to determine the safety and efficacy of TAK-559, once daily (QD), combined with glyburide in treating Type 2 Diabetes.

开始日期2003-11-01

申办/合作机构

Takeda Pharmaceutical Co., Ltd.

NCT00763022 / Completed临床3期

A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Parallel Study of the Safety and Efficacy of TAK-559 Compared to Placebo in the Treatment of Patients With Type 2 Diabetes Mellitus

The purpose of this study was to determine the safety and efficacy of TAK-559, once daily (QD), in Type 2 Diabetes subjects.

开始日期2003-11-01

申办/合作机构

Takeda Pharmaceutical Co., Ltd.

100 项与伊格列扎相关的临床结果

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100 项与伊格列扎相关的转化医学

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100 项与伊格列扎相关的专利（医药）

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6

项与伊格列扎相关的文献（医药）

2021-05-01·Saudi Journal of Biological Sciences3区 · 生物学

Screening of drug databank against WT and mutant main protease of SARS-CoV-2: Towards finding potential compound for repurposing against COVID-19

3区 · 生物学

ArticleOA

作者: Abohashrh, Mohammed ; Baig, Mohammad Hassan ; Irfan, Safia ; Ahmad, Irfan ; Alam, Mohammad Mahtab ; Sharma, Tanuj ; Dong, Jae-June

Although several pharmacological agents are under investigation to be repurposed as therapeutic against COVID-19, not much success has been achieved yet. So, the search for an effective and active option for the treatment of COVID-19 is still a big challenge. The Spike protein (S), RNA-dependent RNA polymerase (RdRp), and Main protease (Mpro) are considered to be the primary therapeutic drug target for COVID-19. In this study we have screened the drugbank compound library against the Main Protease. But our search was not limited to just Mpro. Like other viruses, SARS-CoV-2, have also acquired unique mutations. These mutations within the active site of these target proteins may be an important factor hindering effective drug candidate development. In the present study we identified important active site mutations within the SARS-CoV-2 Mpro (Y54C, N142S, T190I and A191V). Further the drugbank database was computationally screened against Mpro and the selected mutants. Finally, we came up with the common molecules effective against the wild type (WT) and all the selected Mpro. The study found Imiglitazar, was found to be the most active compound against the wild type of Mpro. While PF-03715455 (Y54C), Salvianolic acid A (N142S and T190I), and Montelukast (A191V) were found to be most active against the other selected mutants. It was also found that some other compounds such as Acteoside, 4-Amino-N- {4-[2-(2,6-Dimethyl-Phenoxy)-Acetylamino]-3-Hydroxy-1-Isobutyl-5-Phenyl-Pentyl}-Benzamide, PF-00610355, 4-Amino-N-4-[2-(2,6-Dimethyl-Phenoxy)-Acetylamino]-3-Hydroxy-1-Isobutyl-5-Phenyl-Pentyl}-Benzamide and Atorvastatin were showing high efficacy against the WT as well as other selected mutants. We believe that these molecules will provide a better and effective option for the treatment of COVID-19 clinical manifestations.

2011-09-09·The Open Medicinal Chemistry Journal

Medicinal Chemistry and Actions of Dual and Pan PPAR Modulators

Article

作者: Ernest Adeghate ; Kornelia Tekes ; Huba Kalasz ; Mohamed Y Hasan ; Abdu Adem

Peroxisome proliferator-activated receptor (PPAR) agonists are used as adjunct therapy in the treatment of diabetes mellitus. Fibrates, including fenofibrate, gemfibrozil, benzafibrate, ciprofibrate, and clofibrate act on PPAR alpha to reduce the level of hypertriglyceridemia. However, agonists (ligands) of PPAR-beta/delta receptors, such as tesaglitazar, muraglitazar, ragaglitazar, imiglitazar, aleglitazar, alter the body's energy substrate preference from glucose to lipids and hence contribute to the reduction of blood glucose level. Glitazones or thiazolidinediones on the other hand, bind to PPAR-gamma receptors located in the nuclei of cells. Activation of PPAR-gamma receptors leads to a decrease in insulin resistance and modification of adipocyte metabolism. They reduce hyperlipidaemia by increasing the level of ATP-binding cassette A1, which modifies extra-hepatic cholesterol into HDL. Dual or pan PPAR ligands stimulate two or more isoforms of PPAR and thereby reduce insulin resistance and prevent short- and long-term complications of diabetes including micro-and macroangiopathy and atherosclerosis, which are caused by deposition of cholesterol. This review examines the chemical structure, actions, side effects and future prospects of dual and pan PPAR agonists.

2007-10-01·Metabolism1区 · 医学

A novel peroxisome proliferator–activated receptor α/γ dual agonist ameliorates dyslipidemia and insulin resistance in prediabetic rhesus monkeys

1区 · 医学

Article

作者: Barbara C. Hansen ; Gheorghe T. Braileanu ; Shi-Ying Ding ; Katsuhiko Ito ; Xenia T. Tigno

TAK-559, a newly developed non-thiazolidinedione, activates both peroxisome proliferator-activated receptors alpha and gamma. We investigated the effects of TAK-559 on dyslipidemia and insulin resistance in nonhuman primates. Five adult male obese prediabetic rhesus monkeys were studied on vehicle and after TAK-559 treatment (0.3, 1.0, 3.0 mg/kg per day) for a total of 12 weeks. No significant changes were observed in body weight and fasting plasma glucose, total plasma cholesterol, very low-density lipoprotein-triglyceride, and low-density lipoprotein cholesterol levels. TAK-559 treatment resulted in significant elevation of circulating high-density lipoprotein (HDL) cholesterol levels, consisting of an increase in large HDL particles and a decrease in small dense HDL particles. Nuclear magnetic resonance data exhibited a less atherogenic lipoprotein profile with treatment. Plasma triglyceride and apolipoprotein B-100 levels decreased, whereas apolipoprotein A-I increased during TAK-559 treatment. Hyperinsulinemia and insulin resistance (quantitative insulin sensitivity check index and homeostasis model assessment) were significantly corrected with the highest dose of 3.0 mg/kg per day in these prediabetic monkeys. In addition, no adverse effects on representative liver function parameters were observed during the study period. These results suggest that TAK-559 had beneficial effects on lipoprotein profiles and insulin sensitivity, without any side effect on body weight, which suggests that TAK-559 may provide a potentially safe approach for delaying the onset of type 2 diabetes mellitus and may reduce the risk of cardiovascular disease. The positive effects of TAK-559 in nonhuman primates have led to further clinical trials of TAK-559 in Europe and the United States.

100 项与伊格列扎相关的药物交易

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