ALT-2074(ALT-2074) - 药物靶点：Cell adhesion molecules x GPx_专利_临床

概要

基本信息

药物类型

小分子化药

别名

+ [1]

靶点

Cell adhesion molecules x GPx

作用机制

细胞粘附分子抑制剂、GPx刺激剂(谷胱甘肽过氧化物酶刺激剂)

治疗领域

免疫系统疾病心血管疾病消化系统疾病+ [5]

在研适应症-

非在研适应症

急性冠状动脉综合征溃疡性结肠炎冠心病+ [7]

原研机构

GT Biopharma, Inc.

在研机构-

非在研机构

Synvista Therapeutics, Inc.

GT Biopharma, Inc.

最高研发阶段终止临床2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C10H13NSe

InChIKeyFXRYWOJYVGJZLE-UHFFFAOYSA-N

CAS号173026-17-0

关联

3

项与 ALT-2074 相关的临床试验

NCT00782613 / Terminated临床2期

Randomized, Double-Blind, Placebo-Controlled Study of Efficacy and Wafety of Topical ALT-2074 (SYI-2074) for Treatment of Chronic

The primary objective of this study will be to evaluate the efficacy of topical ALT-2074 applied twice daily for 28 days for treatment of chronic plaque psoriasis in adult subjects.
The secondary objective will be to evaluate the safety of topical ALT-2074 applied twice daily for 28 days for treatment of chronic plaque psoriasis in adult subjects.
Tertiary objectives will be to provide visual documentation of the improvement of psoriatic plaques treated with ALT-2074 using digital photography, and to determine the extent of systemic absorption of topically applied ALT-2074 based on a pharmacokinetic measurement of blood concentration.

开始日期2008-11-01

申办/合作机构

Synvista Therapeutics, Inc.

NCT00491543 / Completed临床2期

A Randomized, Double-Blind, Placebo-Controlled, Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of ALT 2074 in Subjects With Type 2 Diabetes Who Have a Haptoglobin Type 2-2 Genotype and Coronary Artery Disease

ALT-2074 (BXT-51072) belongs to a class of drugs called "glutathione peroxidase mimics." ALT-2074 works by imitating a substance produced in various tissues in the body, which prevents damage of the heart and blood vessels. Diabetic patients with a haptoglobin 2-2 genotype have poor cardiovascular clinical outcomes.
The purpose of this study is to assess the safety, the pharmacokinetic profile and characterize the effect on biomarkers of inflammation and oxidative stress of repeat doses of ALT 2074. Subjects must be diabetic, with evidence of coronary artery disease and a haptoglobin 2-2 genotype

开始日期2007-06-01

申办/合作机构

Synvista Therapeutics, Inc.

NCT00320502 / Completed临床2期

A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Determine the Effects of BXT-51072 on CK-MB in High-Risk Type 2 Diabetic Patients Undergoing Elective Percutaneous Coronary Intervention

The purpose of this study is to determine the safety and feasibility of BXT-51072 as a cardioprotective agent in diabetics undergoing elective angioplasty / percutaneous intervention (PCI), a procedure to "open" coronary arteries.
BXT-51072 belongs to a class of drugs called "glutathione peroxidase mimics." BXT-51072 works by imitating a substance produced in various tissues in the body, which prevents damage of the heart and blood vessels.

开始日期2006-05-01

申办/合作机构

Synvista Therapeutics, Inc.

100 项与 ALT-2074 相关的临床结果

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100 项与 ALT-2074 相关的转化医学

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100 项与 ALT-2074 相关的专利（医药）

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8

项与 ALT-2074 相关的文献（医药）

2010-09-01·Journal of Clinical Neuroscience4区 · 医学

Vasospasm after subarachnoid hemorrhage in haptoglobin 2-2 mice can be prevented with a glutathione peroxidase mimetic

4区 · 医学

Article

作者: Ali Kooshkabadi ; Andrew Levy ; Slava Sher ; Rafael J. Tamargo ; Michael T. Froehler ; Shany Blum ; Rachel Miller-Lotan

Vasospasm after subarachnoid hemorrhage (SAH) is attributable to inflammation and oxidative stress associated with extracellular hemoglobin (Hb). Haptoglobin (Hp) binds free Hb and the Hp-Hb complex is cleared by macrophages, and the Hp-2 isoform of Hp is associated with more oxidative stress and more severe vasospasm. We hypothesized that treatment with an anti-oxidant, the glutathione peroxidase mimetic SYI-2074, would reduce vasospasm after SAH in Hp-2 mice. We found that SAH induced significant vasospasm in Hp-2 mice (lumen patency reduced to 65.9%), but no vasospasm was seen in mice that received SYI-2074 after SAH (lumen patency of 98.7%). We conclude that vasospasm after SAH in Hp-2 mice can be prevented with SYI-2074, suggesting that oxidative stress contributes significantly to vasospasm.

2007-01-01·Journal of the American College of Cardiology1区 · 医学

Haptoglobin Genotype Determines Myocardial Infarct Size in Diabetic Mice

1区 · 医学

Article

作者: Shany Blum ; Rachel Miller-Lotan ; Franklin G. Berger ; Ran Kremer ; Doron Aronson ; Xiaoming Fu ; Andrew P. Levy ; Renliang Zhang ; Roy Asaf ; Stanley L. Hazen ; Rabea Asleh ; Nina S. Levy ; Julia Guetta

OBJECTIVESWe sought to understand the importance of oxidative stress in explaining why the haptoglobin (Hp) genotype determines myocardial infarction (MI) size in diabetes mellitus (DM).BACKGROUNDTwo common alleles (1 and 2) exist at the Hp locus in humans. The Hp 2 allele is associated with increased MI size in individuals with DM. In vitro, the Hp 2 protein is associated with increased generation of oxidatively active iron, whereas the Hp 1 protein is associated with increased production of the antioxidant cytokine interleukin (IL)-10.METHODSMyocardial infarction was produced by myocardial ischemia-reperfusion (IR) in DM C57BL/6 mice carrying the Hp 1 or Hp 2 allele. Myocardial oxidative stress after IR was assessed using electrospray ionization mass spectrometry. Redox active iron and IL-10 were measured in the serum after IR.RESULTSMyocardial infarction size was significantly larger in Hp 2 mice as compared with Hp 1 mice (44.3 +/- 9.3% vs. 21.0 +/- 4.0%, p = 0.03), and these larger infarctions were associated with a significant increase in a panel of hydroxyl-eicosatetraenoic acids. Redox active iron was greater in Hp 2 mice (0.45 +/- 0.11 micromol/l vs. 0.14 +/- 0.05 micromol/l, p = 0.02), whereas IL-10 was greater in Hp 1 mice (85.8 +/- 12.9 pg/microl vs. 46.7 +/- 10.8 pg/microl, p = 0.04) after IR. Administration of an antioxidant (BXT-51072) to Hp 2 mice reduced myocardial injury after IR by more than 80% (p = 0.003), but no myocardial protection was provided by the antioxidant to Hp 1 mice.CONCLUSIONSThe increased MI size in DM Hp 2 mice occurring after IR may be due to increased oxidative stress.

2000-12-01·American Journal of Physiology-Cell Physiology3区 · 生物学

Shear stress induces iNOS expression in cultured smooth muscle cells: role of oxidative stress

3区 · 生物学

Article

作者: Gonzalez, Walter ; Messika-Zeitoun, David ; Michel, Jean-Baptiste ; Gosgnach, Willy ; Philipe, Monique

After deendothelialization, the most luminal smooth muscle cells of the neointima are in contact with blood flow and express inducible nitric oxide synthase (iNOS) in vivo. We hypothesized that shear stress may be a stimulus for this iNOS overexpression. We have thus submitted smooth muscle cells to laminar shear and measured the iNOS expression. Shear stress (20 dyn/cm2) induced iNOS mRNA and protein expression, whereas brain NOS mRNA expression was decreased. Conversely, nitrite production was increased. This production was blocked by a selective iNOS inhibitor. Pyrrolidine dithiocarbamate, an antioxidant molecule, and BXT-51072, a gluthation peroxidase mimic, both inhibited the shear-induced iNOS expression. Shear stress also increased the expression of both membrane subunits of NADPH oxidase p22phox and Mox-1. Shear stress activated the redox-sensitive nuclear translocation of the transcription nuclear factor-κB (NF-κB) and stimulated the degradation of both cytosolic inhibitors κB α and β. These results show that shear stress can induce iNOS expression and nitrite production in smooth muscle cells and suggest that this regulation is probably mediated by oxidative stress-induced NF-κB activation.

100 项与 ALT-2074 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB05631

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
斑块状银屑病	临床2期	以色列	Synvista Therapeutics, Inc.	2008-11-01
冠心病	临床2期	美国	Synvista Therapeutics, Inc.	2007-06-01
2型糖尿病	临床2期	美国	Synvista Therapeutics, Inc.	2007-06-01
非胰岛素依赖型糖尿病2	临床2期	以色列	Synvista Therapeutics, Inc.	2006-05-01
急性冠状动脉综合征	临床2期	-	GT Biopharma, Inc.	-
急性冠状动脉综合征	临床2期	-	GT Biopharma, Inc.	-
溃疡性结肠炎	临床2期	美国	GT Biopharma, Inc.	-
溃疡性结肠炎	临床2期	-	Synvista Therapeutics, Inc.	-
慢性阻塞性肺疾病	临床2期	美国	-	-
成人呼吸窘迫综合征	临床2期	英国	-	-