A 3-month Randomized, Double-Blind, Placebo-Controlled, Feasibility Study to Evaluate the Effects of MSDC-0160 on Brain Glucose Utilization, Cognition, Safety and Tolerability in Older Persons With Mild Alzheimer's Disease

This study will evaluate the effect of 150 mg MSDC-0160 taken daily for 90 days compared to the effect of placebo on changes in brain glucose utilization using FDG-PET and cognition in older persons with mild Alzheimer's disease. Safety and tolerability of MSDC-0160 in this population will also be studied. These results will be used to design larger studies of MSDC-0160 in persons with mild Alzheimer's disease.

开始日期2011-07-01

申办/合作机构

Metabolic Solutions Development Co. LLC

NCT01103414

/ Completed临床2期

Phase 2B, Randomized, Double-Blind, Comparator- & Placebo-Controlled, Dose Ranging Study to Evaluate Safety, Tolerability & Efficacy of 3 Dose Levels of Mitoglitazone in Type 2 Diabetic Patients

The purpose of this study is to evaluate the safety, tolerability and efficacy of three dose levels of Mitoglitazone™ (MSDC-0160) in patients with type 2 diabetes.

开始日期2010-09-01

申办/合作机构

Metabolic Solutions Development Co. LLC

NCT00760578

/ Completed临床2期

A Phase 2A, Randomized, Double-Blind, Comparator- and Placebo-Controlled, Multiple-Dose Study to Evaluate the Safety, Tolerability and Efficacy of Two Dose Levels of Mitoglitazone™ in Type 2 Diabetic Patients

The purpose of this study is to determine if MSDC-0160 is effective in the treatment of Type 2 diabetes.

开始日期2008-09-01

申办/合作机构

Metabolic Solutions Development Co. LLC

100 项与 Mitoglitazone 相关的临床结果

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100 项与 Mitoglitazone 相关的转化医学

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100 项与 Mitoglitazone 相关的专利（医药）

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项与 Mitoglitazone 相关的文献（医药）

2025-05-01·JOURNAL OF BIOLOGICAL CHEMISTRY

Glyceraldehyde-3-phosphate dehydrogenase/1,3-bisphosphoglycerate-NADH as key determinants in controlling human retinal endothelial cellular functions: Insights from glycolytic screening

Article

作者: Awad, Ahmed M ; Ibrahim, Ahmed S ; Shawky, Mohamed ; Naghdi, Armaan ; Yumnamcha, Thangal ; Oska, Nicole ; Eltanani, Shaimaa ; Singh, Lalit Pukhrambam

Maintaining barrier integrity, along with cell adhesion to the extracellular matrix and the subsequent process of cell spreading, are essential functions of endothelial cells, including human retinal endothelial cells (HRECs). Disruptions in these processes can lead to vision-threatening conditions like diabetic retinopathy. However, the bioenergetic mechanisms that regulate HREC barrier function and cell spreading remain incompletely understood. This study investigates the role of lower glycolytic components in modulating these critical functions of HRECs. In vitro, Electric Cell-Substrate Impedance Sensing (ECIS) technology was used to measure real-time changes in HREC barrier integrity (electrical resistance) and cell spreading (capacitance). Pharmacological inhibitors targeting lower glycolytic components were tested: heptelidic acid for glyceraldehyde-3-phosphate dehydrogenase (GAPDH), NG-52 for phosphoglycerate kinase (PGK), shikonin for pyruvate kinase M (PKM), galloflavin for lactate dehydrogenase (LDH), AZD3965 for lactate transporter (MCT1), and MSDC-0160 for the mitochondrial pyruvate carrier (MPC). GAPDH knockdown was performed using siRNA, and cell viability was assessed via LDH release assays. For in vivo studies, wild-type C57BL/6J mice received intravitreal injections of heptelidic acid, while control mice received the vehicle (dimethyl sulfoxide). Retinal vascular permeability was assessed by fluorescein angiography (FA) and retinal albumin leakage. The most significant decrease in electrical resistance and increase in capacitance of HRECs were observed following the dose-dependent inhibition of GAPDH and the resulting reduction in 1,3-bisphosphoglycerate (1,3-BPG) and NADH by heptelidic acid. LDH level analysis at 24 to 48 h post-treatment with heptelidic acid (1 and 10 μM) showed no significant difference compared to controls, indicating that the observed disruption of HREC functionality was not due to cell death. Supporting these findings, inhibition of downstream glycolytic steps that result in the accumulation of 1,3-BPG and NADH, such as treatment with NG-52 for PGK or shikonin for PKM, led to a significant increase in electrical resistance and a decrease in cell capacitance. Furthermore, GAPDH knockdown via siRNA also led to a significant decrease in cellular resistance in HRECs. In vivo, FA imaging demonstrated that intravitreal injection of heptelidic acid led to significant retinal vascular leakage, as further supported by increased albumin extravasation in treated eyes. Conversely, pharmacological inhibition of other lower glycolytic components, including LDH, MCT, and MPC, did not significantly alter HREC barrier function or spreading behavior. This study highlights the distinct roles of lower glycolytic components in regulating HREC functionality. GAPDH and its downstream products (1,3-BPG and NADH) are shown to play a pivotal role in maintaining barrier integrity and promoting HREC adhesion and spreading. These findings guide the development of targeted interventions that modulate HREC bioenergetics to treat endothelial dysfunction in various retinal disorders, while minimizing potential adverse effects on healthy endothelial cells.

2023-04-01·Toxicology and applied pharmacology

Mitoglitazone ameliorates renal ischemia/reperfusion injury by inhibiting ferroptosis via targeting mitoNEET

Article

作者: Wang, Zhigang ; Feng, Chenghao ; Zhang, Di ; Feng, Yi ; Yan, Yongchuang ; Qiu, Yang ; Zhao, Jie ; Hu, Mingyao ; Hou, Xinyue ; Zhang, Luyu ; Qi, Yuanbo

Ischemia/reperfusion- (I/R-) induced injury is unavoidable and a major risk factor for graft failure and acute rejection following kidney transplantation. However, few effective interventions are available to improve the outcome due to the complicated mechanisms and lack of appropriate therapeutic targets. Hence, this research aimed to explore the effect of the thiazolidinedione (TZD) compounds on I/R-induced kidney damage. One of the main causes of renal I/R injury is the ferroptosis of renal tubular cells. In this study, compared with the antidiabetic TZD pioglitazone (PGZ), we found its derivative mitoglitazone (MGZ) exerted significantly inhibitory effects on erastin-induced ferroptosis by suppressing mitochondrial membrane potential hyperpolarization and lipid ROS production in HEK293 cells. Moreover, MGZ pretreatment remarkably alleviated I/R-induced renal damages by inhibiting cell death and inflammation, upregulating the expression of glutathione peroxidase 4 (GPX4), and reducing iron-related lipid peroxidation in C57BL/6 N mice. Additionally, MGZ exhibited excellent protection against I/R-induced mitochondrial dysfunction by restoring ATP production, mitochondrial DNA copy numbers, and mitochondrial morphology in kidney tissues. Mechanistically, molecular docking and surface plasmon resonance experiments demonstrated that MGZ exhibited a high binding affinity with the mitochondrial outer membrane protein mitoNEET. Collectively, our findings indicated the renal protective effect of MGZ was closely linked to regulating the mitoNEET-mediated ferroptosis pathway, thus offering potential therapeutic strategies for ameliorating I/R injuries.

2022-10-01·Molecular neurobiology

Re-routing Metabolism by the Mitochondrial Pyruvate Carrier Inhibitor MSDC-0160 Attenuates Neurodegeneration in a Rat Model of Parkinson’s Disease

Article

作者: Goutaudier, Raphael ; Mallet, David ; Boulet, Sabrina ; Carnicella, Sebastien ; Fauvelle, Florence ; Barbier, Emmanuel L ; Colca, Jerry R

A growing body of evidence supports the idea that mitochondrial dysfunction might represent a key feature of Parkinson's disease (PD). Central regulators of energy production, mitochondria, are also involved in several other essential functions such as cell death pathways and neuroinflammation which make them a potential therapeutic target for PD management. Interestingly, recent studies related to PD have reported a neuroprotective effect of targeting mitochondrial pyruvate carrier (MPC) by the insulin sensitizer MSDC-0160. As the sole point of entry of pyruvate into the mitochondrial matrix, MPC plays a crucial role in energetic metabolism which is impacted in PD. This study therefore aimed at providing insights into the mechanisms underlying the neuroprotective effect of MSDC-0160. We investigated behavioral, cellular, and metabolic impact of chronic MSDC-0160 treatment in unilateral 6-OHDA PD rats. We evaluated mitochondrially related processes through the expression of pivotal mitochondrial enzymes in dorsal striatal biopsies and the level of metabolites in serum samples using nuclear magnetic resonance spectroscopy (NMR)-based metabolomics. MSDC-0160 treatment in unilateral 6-OHDA rats improved motor behavior, decreased dopaminergic denervation, and reduced mTOR activity and neuroinflammation. Concomitantly, MSDC-0160 administration strongly modified energy metabolism as revealed by increased ketogenesis, beta oxidation, and glutamate oxidation to satisfy energy needs and maintain energy homeostasis. MSDC-0160 exerts its neuroprotective effect through reorganization of multiple pathways connected to energy metabolism.

项与 Mitoglitazone 相关的新闻（医药）

2021-04-04

·创药网

阿尔茨海默病治疗新进展（下篇）

▲限时免费参会名额倒计时🔥，1900+已报名阿尔茨海默病（Alzheimer's Disease，AD）是一种神经退行性疾病，随着全球人口老龄化的到来，AD正在给全球带来沉重的疾病负担。开发治疗AD的有效疗法一直是艰巨的挑战，但药物研发者仍抱有期翼，研发管线上疾病修饰类药物数量仍在增加。随着研究的不断深入，更多的风险基因、生物标志物、靶标机制被发现，临床候选药物涉及的靶标也更加多样化。本文下篇就近期报道的AD治疗的新疗法、新机制、新靶标以及新的诊断技术等进展情况进行汇总，供研发人员参考。 AD治疗新进展糖代谢相关靶标近年来，靶向葡萄糖代谢的AD新型疗法成为当下研究的新方向。利拉鲁肽、索马鲁肽、度拉鲁肽等胰高血糖素样肽-1受体（GLP1R）激动剂，已显现出改善认知的作用，2020年12月，诺和诺德宣布将开展口服索马鲁肽治疗AD的Ⅲ期临床研究。利拉鲁肽用于AD治疗的临床Ⅱ期研究尚在进行中。除了GLP1R，靶向过氧化物酶体增殖剂激活受体（PPARs）的药物有2个已进入临床试验（Ⅱ期），分别为T3D-959和MSDC-0160。该靶标广泛参与机体的脂质代谢、糖代谢、能量代谢、血压调节、细胞生长分化及生殖过程。近来，也有多项研究揭示了糖代谢与AD病理的联系。2020年4月，Nature Medicine刊登了一项大型AD相关蛋白研究的结果，题为“Large-scale proteomic analysis of Alzheimer’s disease brain and cerebrospinal fluid reveals early changes in energy metabolism associated with microglia and astrocyte activation”。该研究采集了2000名AD患者的脑组织，以及400份脑脊髓液样本，分析了3000多种蛋白质的表达模式。研究表明，葡萄糖代谢蛋白与AD相关的认知障碍关系密切。能够保护大脑中支持细胞（星形胶质细胞和小胶质细胞）的蛋白，在AD的病理过程中也起着关键作用。这一研究是基于先前Emory医学院和美国国立卫生研究院（NIH）下属的国家老龄研究所（NIA）的共同发现：大脑葡萄糖分解过程异常与大脑中淀粉样斑块的形成和记忆丧失的发生有关。控制葡萄糖分解并转化成能量的蛋白，在AD患者的脑脊液中有所升高。这些蛋白的含量上升，也可在有发病迹象、但尚未出现明显症状的群体中看到。研究者还观察到，控制葡萄糖代谢的蛋白变化促使神经胶质细胞发生抗炎反应。AD的发生，可能是始于大脑对神经细胞的保护意图。2021年1月，中国科学技术大学神经退行性疾病研究中心申勇课题组在期刊Alzheimer's & Dementia上，发表题为“Increased β-site APP cleaving enzyme 1-mediated insulin receptor cleavage in type 2 diabetes mellitus with cognitive impairment”的研究论文。研究发现AD致病关键蛋白酶，β-淀粉样前体蛋白（APP）切割酶（BACE1）在2型糖尿病患者体内异常升高，通过剪切胰岛素受体而影响胰岛素敏感性参与胰岛素抵抗的发生。BACE1通过促进淀粉样蛋白（Aβ）的产生，且可能通过促进胰岛素抵抗进而增加2型糖尿病患者的认知损伤发生风险。BACE1不仅是联系2型糖尿病与认知障碍发生的桥梁，也是改善2型糖尿病患者体内胰岛素抵抗以及2型糖尿病相关认知障碍发生的关键靶标。炎症相关靶标神经炎症被认为是导致AD发病的潜在机制之一，目前已有一些具有抗炎效果的药物和调控大脑免疫系统的药物进入临床，如靶向晚期糖基化终产物受体（RAGE）的Azeliragon，该药物曾进入临床Ⅲ期，但目前已停研；由吸入型色甘酸钠和口服布洛芬组成的复方制剂ALZT-OP1（临床Ⅲ期），P2Y6受体调节剂GC-021109（临床Ⅰ期），肿瘤坏死因子（TNF）抑制剂XPro1595（临床Ⅰ期）等。一些新的炎症靶标也在被报道。2020年6月，发表在Neurotherapeutics上的一项研究“Pharmacological Inhibition of Soluble Epoxide Hydrolase as a New Therapy for Alzheimer’s Disease”指出，抑制可溶性环氧化物水解酶（sEH）的作用可减少神经炎症过程，改善机体的内源性反应，并减少引起AD这类痴呆的神经元损伤和死亡。环氧二十碳三烯酸（Epoxyeicosatrienoic acids，EET）是一种能在高血压或糖尿病等病理状况下减轻炎症反应的分子，而sEH酶可以使其失去抗炎活性，从而引发炎症。基于sEH的功能，研究人员分析了两种AD动物模型，在第一部分研究中，与对照组相比，两种动物模型中sEH的表达均增加。进一步研究发现，在AD患者的脑样本中sEH的表达同样也增加了。该研究证实了sEH在AD发展中的作用，并明确了sEH是AD和其它神经炎症特征疾病的潜在治疗靶标。2020年9月，Nature在线发表了题为“The innate immunity protein IFITM3 modulates γ-secretase in Alzheimer's disease”的文章，研究指出干扰素诱导跨膜蛋白3（IFITM3）参与对病原体的免疫应答，能改变γ-分泌酶（一种将前体蛋白切成β-淀粉样蛋白片段的酶）的活性。而且敲除IFITM3会降低γ-分泌酶的活性，从而减少AD小鼠模型中淀粉样斑块的形成数量。IFITM3具有广泛的抗病毒活性，是抵御感染的第一道防线，同时IFITM3也是γ-分泌酶复合物的一部分，其表达水平与γ-分泌酶活性相关。在分析了大量的小鼠大脑样本后，研究人员发现，炎症标记物和IFITM3的含量随着年龄的增长而增加，而且在一部分迟发性阿尔茨海默病（LOAD）患者的脑样本中观察到了IFITM3表达的增加。IFITM3或可作为AD的生物标志物和潜在靶标。声光刺激治疗AD的创新疗法在第15届阿尔茨海默病和帕金森病国际大会（AD/PD 2021）上，Cognito Therapeutics公司宣布，该公司通过声光刺激来治疗AD的创新数字疗法，在Ⅱ期临床试验中获得积极结果，该创新疗法具有改变AD疾病进程的潜力。这项Ⅱ期临床试验（NCT-03556280）是一项多中心随机对照临床试验，纳入了76名年龄在50岁或以上的轻度至中度AD患者（MMSE 14-26），在治疗期间，他们随机在家接受40Hz非侵入性声光刺激或假刺激，每天一小时。在随后的6个月里，研究人员通过多种检测手段衡量了患者的日常生活能力（使用名为ADCS-ADL的评分），记忆和认知能力（使用MMSE评分），并且使用核磁共振成像（MRI）来评估大脑体积的变化。试验结果表明，与对照组（n=20）相比，治疗组（n=33）的日常生活能力评分下降速度减缓了84%，记忆和认知能力衰退速度降低了83%，大脑萎缩和脑容量损失的速度也减缓了61%。所有这些变化都达到统计显著标准。该声光刺激疗法在今年1月份还获得美国FDA授予的突破性医疗器械认定。此项疗法源于麻省理工学院（MIT）蔡立慧教授的突破性发现。早在2016年，她的团队就在Nature上发表论文，显示在小鼠的AD模型中，通过LED灯发出特殊频率的闪光，能够减少小鼠大脑中的淀粉样蛋白沉积。随后，蔡立慧教授团队在Cell和Neuron上发表论文，进一步阐明了利用声光刺激，在小鼠模型中清除淀粉样蛋白沉积，改善小鼠认知能力的作用机制。研究人员发现，频率为40赫兹（Hz）的声光刺激联合使用时，不但能够激发小胶质细胞的反应，帮助清除淀粉样蛋白，而且还可以维持神经突触的数量和健康。另有研究探索了超声波治疗对AD患者的潜在益处。研究人员发现，使用聚焦超声结合微泡治疗，可以在由人类内皮细胞形成的血脑屏障中创造开口，从而向AD患者递送靶向药物。通过聚焦超声和微泡治疗，可以削弱血脑屏障细胞之间的联系，从而让脑组织吸收药物治疗成为可能。该研究于2020年5月发表在Stem Cell Reports杂志上。早期诊断技术脑脊液（CSF）淀粉样蛋白、脑脊液tau蛋白、核磁共振成像（MRI）和淀粉样正电子发射断层扫描（PET）已作为生物标志物被应用于多项临床试验中。近来有更多的研究提出了新型生物标记物或可用于AD的早期诊断。2020年在JAMA上发表的一项血液检测P-tau217（217号苏氨酸磷酸化的Tau蛋白）诊断AD的大型国际研究结果。结果显示，1402名参与者中，检测P-tau217的血检在区分AD和其它神经退行性疾病方面的准确性在89%-98%之间。检测P-tau217水平的血检诊断AD的准确程度超过检验血液中神经纤维丝轻链（NfL）、淀粉样蛋白，也超过基于MRI成像的检测。它的准确度和PET扫描大脑Tau蛋白和检测脑脊液中淀粉样蛋白、Tau蛋白生物标志物的检测相当。另一项2021年1月Nature Medicine上的一项研究显示，血液和脊髓液中的NfL水平在患者开始出现神经退行性病变之前就已经开始上升，比发病早了16年多。NfL的增长速度与大脑中一个叫做楔前叶的区域的萎缩有关，并且NfL水平快速上升的患者在认知测试中的表现更差。视网膜筛查或许也为AD早期诊断提供一个新的路径。近年越来越多的研究证实AD患者的视网膜受到影响，如视网膜神经节细胞（RGCs）和神经纤维层（NFL）的丢失、黄斑神经节细胞复合体的恶化和视神经轴突的缩小等。当与脑成像、生物标记物和神经心理学评估相结合时，眼睛可以潜在地改善现有的AD风险评估、检测和监测方法。由于AD进展的分子机制尚不清楚，导致诸多新药研发在此领域折戟。但随着蛋白质组学、基因组学、分子影像、AI技术的进展，更多的风险基因、生物标志物、靶标以及机制被发现，助力该疾病的诊断和新药研发。早期诊断可减缓病理进程，放慢大脑受损速度，对AD的预防和治疗具有重大意义。当前，AD疾病修饰类药物研发的靶标越来越趋于多样化，除了经典的β-淀粉样蛋白（Aβ）和Tau蛋白，与炎症、代谢异常、肠道菌群、粒体自噬、神经发生、神经元保护、免疫调节等相关靶标正在吸引药物研发者的注意。【参考资料】 1. Alzheimer's Disease International (ADI). World Alzheimer Report 2018. https://www.alzint.org/resource/world-alzheimer-report-2018/. 2. Alzheimer’s Association. 2021 Alzheimer’s Disease Facts and Figures. https://www.alz.org/media/Documents/alzheimers-facts-and-figures.pdf. 3. Jia L, Du Y, Chu L, et al. Prevalence, risk factors, and management of dementia and mild cognitive impairment in adults aged 60 years or older in China: a cross-sectional study. Lancet Public Health. 2020, 5(12): e661-e671. 4. Cummings J, Lee G, Ritter A, Sabbagh M, et al. Alzheimer's disease drug development pipeline: 2020. Alzheimers Dement (N Y)., 2020, 6(1): e12050. 5. Oikari LE, Pandit R, Stewart R, et al. Altered Brain Endothelial Cell Phenotype from a Familial Alzheimer Mutation and Its Potential Implications for Amyloid Clearance and Drug Delivery. Stem Cell Reports, 2020, 14(5): 924-939. 6. Johnson, E.C.B., Dammer, E.B., Duong, D.M. et al. Large-scale proteomic analysis of Alzheimer’s disease brain and cerebrospinal fluid reveals early changes in energy metabolism associated with microglia and astrocyte activation. Nature Medicine, 2020, 26: 769–780. 7. Bao H, Liu Y, Zhang M, Chen Z, Zhang W, Ge Y, Kang D, Gao F, Shen Y. Increased β-site APP cleaving enzyme1-mediated insulin receptor cleavage in type 2 diabetes mellitus with cognitive impairment. Alzheimers Dement. 2021 Jan 7. 8. Griñán-Ferré C, Codony S, Pujol E, et al. Pharmacological Inhibition of Soluble Epoxide Hydrolase as a New Therapy for Alzheimer's Disease. Neurotherapeutics, 2020, 17(4): 1825-1835. 9. Hur JY, Frost GR, Wu X, et al. The innate immunity protein IFITM3 modulates γ-secretase in Alzheimer's disease. Nature, 2020, 586(7831): 735-740. 10. Gupta VB, Chitranshi N, denHaan J, et al. Retinal changes in Alzheimer's disease- integrated prospects of imaging, functional and molecular advances. Prog Retin Eye Res. 2020, 2: 100899. 版权声明：本文转自创药网，如不希望被转载的媒体或个人可与我们联系，我们将立即删除【关于药融圈】药融圈围绕我国生物医药产业链，针对生物医药大数据、技术和资本投资、药融园(产业园)等开展系列系统性工作，促进我国生物医药产业健康发展，完善产业链，共同面对全球合作和竞争。点分享点点赞点在看

2011-06-21

·BioSpace

Metabolic Solutions Development Company to Present Recent Findings on the Therapeutic Potential of Increasing Brown Fat in the Treatment of Diabetes at Annual American Diabetes Association Conference

KALAMAZOO, Mich., June 21, 2011 /PRNewswire/ -- Metabolic Solutions Development Company (MSDC) and collaborators will present their research providing insights into the therapeutic potential of increasing brown adipose tissue in the treatment of diabetes and the unique mechanism of action of the company's novel insulin sensitizers that connects with pathways known to be dysregulated in diabetes at the American Diabetes Association's (ADA) 71st annual Scientific Sessions conference in San Diego, Calif., June 24-28, 2011. The ADA conference is the world's leading scientific and medical meeting focused on diabetes. All sessions at the ADA will be held in the San Diego Convention Center. MSDC Chief Scientific Officer Jerry Colca, Ph.D., will present "Enhancement of Brown Adipose Tissue Development In Vivo by a Novel Insulin Sensitizer" on Saturday, June 25 at 1:45 p.m. PT in Room 29. The presentation will conclude a symposium involving influential thought leaders in the field that focuses on cutting-edge concepts in brown and white adipocyte biology, an emerging important factor in the etiology of diabetes. A key theme of this session will be the therapeutic potential of increasing brown adipose tissue in the treatment of diabetes. The MSDC presentation will suggest that this is possible with the company's small molecule compounds that are currently in clinical trials. "The breakthrough insights MSDC's researchers and collaborators will present at this year's ADA meeting support our view that MSDC's novel insulin sensitizing drugs can treat the root causes of type 2 diabetes and free patients from the adverse side effects of current treatments," said MSDC CEO Stephen Benoit. "We believe these insights are directly related to the success we've observed with MSDC-0160 in Phase 2 clinical trials regarding control of fasting blood glucose without the weight gain and edema associated with the currently marketed insulin sensitizing agents." Colca's presentation, along with four others by MSDC and its collaborating partners at this year's ADA conference, will further elucidate MSDC's novel target and the pathways through which the company's Phase 2 drug candidates are acting. The presentations also will provide new insights into insulin re-sensitization and other potential metabolic benefits of a novel class of insulin sensitizers which could play a pivotal role in the development of new diabetes treatments. "The definition of a new path forward is urgently needed to produce novel therapeutics to adequately treat, and eventually prevent, diabetes," said Colca. "Through these presentations, we will begin to disclose how the novel mechanism of action of our compounds connects with pathways that are known to be dysregulated in diabetes." On Sunday, June 26, MSDC Senior Research Scientist William G. McDonald's poster presentation, "Novel Insulin Sensitizers Enhance Brown Adipose Cell Differentiation by Modulation of Wnt Signaling Pathway," will take place at noon in Hall B. Disruptions in the Wnt signaling pathway are known to predispose persons to type 2 diabetes. MSDC collaborative presentations include: June 25 at 11:30 a.m. PT, "A Mitochondrial Target of Pioglitazone Acutely Regulates Mitochondrial Respiratory Function." The presentation will be held in Hall B. This work from Dr. Anne Murphy's laboratory at the University of California at San Diego will show how a novel mitochondrial target is involved in the direct effect of insulin sensitizers on metabolism. June 25 at 12:30 p.m. PT, "Activating AMPK and Downregulating mTOR with a PPAR-g Sparing TZD Decreases Insulin Resistance & Mediates Human Beta-Cell Rest & Restoration of Insulin Content." The presentation from Dr. Mike McDaniel's laboratory at Washington University in St. Louis demonstrates the potential for this mechanism of action to produce positive effects directly on human insulin-secreting pancreatic beta-cells. June 27 at 1 p.m. PT, "Insulin Resistance in ob/ob Mice Is Ameliorated by Thiazolidinediones That Do Not Activate PPARg." This presentation from the laboratory of Dr. Brian Finck at Washington University in St. Louis provides a detailed comparison of the clinical candidate in mouse models of diabetes with insight into the mechanism of action. MSDC has two novel insulin sensitizers in clinical trials for the treatment of type 2 diabetes. Phase 2a clinical data from the company's lead candidate, MSDC-0160, demonstrated that it improved insulin sensitivity and lowered blood glucose levels in humans without the side effects of the current market leading diabetes medicines. The compound also demonstrated significant improvements in other important metabolic disease parameters, including blood pressure and lipids. A phase 2b study of MSDC-0160 is currently under way in patients with type 2 diabetes and data are expected to be available in January 2012. A Phase 2a trial of MSDC-0602, the company's second drug candidate for the treatment of type 2 diabetes is currently under way. Results of this study are expected to be available in September 2011. A Phase 2b study of MSDC-0602 is targeted to begin in the first quarter of 2012. About Metabolic Solutions Development Company: Metabolic Solutions Development Company ( ) is a drug discovery and development company exploiting novel molecular targets to develop new therapies for metabolic diseases associated with altered mitochondrial function, especially insulin resistance and type 2 diabetes. The company has raised nearly $50 million in support of the development of its pioneer and lead products, MSDC-0160 (currently in Phase 2b) and MSDC-0602 (currently in Phase 2a), which are novel insulin sensitizers that selectively modulate mitochondrial control of certain metabolic-signaling and nutrient-sensing pathways resulting in improved insulin action without fluid retention or weight gain. Founded in 2006 by former Pfizer researchers Jerry Colca, Ph.D. and Rolf Kletzien, Ph.D., MSDC is headquartered in Kalamazoo, Michigan. CONTACT: Tyler Lecceadone SeyferthPR 1-800-435-9539 Lecceadone@seyferthpr.com SOURCE Metabolic Solutions Development Company

小分子药物

100 项与 Mitoglitazone 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB11721

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
阿尔茨海默症	临床2期	美国	Metabolic Solutions Development Co. LLC	2011-07-01
2型糖尿病	临床2期	美国	Metabolic Solutions Development Co. LLC	2008-09-01
帕金森病	临床前	美国	Metabolic Solutions Development Co. LLC	-
多囊肾	临床前	美国	Metabolic Solutions Development Co. LLC	-

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01374438 (CTgov)	临床2期	阿尔茨海默症	29	MSDC-0160 (MSDC-0160 Capsules)	鬱繭醖衊窪構範觸壓艱(選構構衊窪廠蓋鑰艱膚) = 艱衊憲膚顧鏇選廠鏇壓遞壓鹹簾蓋範範夢繭獵 (餘鑰廠網構鏇窪膚膚衊, 0.03) 更多	-	2014-11-05
				Placebo (Placebo Capsules)	鬱繭醖衊窪構範觸壓艱(選構構衊窪廠蓋鑰艱膚) = 壓範壓獵製廠範獵壓願遞壓鹹簾蓋範範夢繭獵 (餘鑰廠網構鏇窪膚膚衊, 0.03) 更多
NCT00760578 (CTgov)	临床2期	2型糖尿病	86	Placebo (Placebo)	膚顧鑰壓製鹽網廠網醖(襯鹹糧鏇壓獵艱網顧鹽) = 簾鹹築壓襯鏇鹽鑰窪鹽鬱鏇齋網鹽積襯糧遞膚 (醖網齋觸醖繭衊艱壓齋, 0.340) 更多	-	2013-05-03
				MSDC-0160 90 mg (MSDC-0160 90 mg)	襯願窪憲衊醖遞餘範鹽(淵範範淵襯鑰構簾積蓋) = 顧衊顧齋窪網鹹鏇廠鏇製鏇衊蓋繭憲襯願繭餘 (衊憲窪夢淵膚鹽積選憲, 0.160) 更多
NCT01103414 (CTgov)	临床2期	2型糖尿病	356	Mitoglitazone (Mitoglitazone 50 mg Capsules)	餘鏇簾醖築醖窪艱願齋(廠範醖遞糧觸簾遞膚築) = 範築繭願餘艱簾襯願壓糧餘選淵鹹鬱膚觸範願 (範鏇餘願鹽鹽範顧衊餘, 4.95) 更多	-	2013-03-22
				Mitoglitazone (Mitoglitazone 100 mg Capsules)	餘鏇簾醖築醖窪艱願齋(廠範醖遞糧觸簾遞膚築) = 製鑰遞壓選衊構壓鏇構糧餘選淵鹹鬱膚觸範願 (範鏇餘願鹽鹽範顧衊餘, 4.74) 更多