ICO-007(ICO-007) - 药物靶点：CRAF_专利_临床

概要

基本信息

药物类型

反义寡核苷酸

别名

靶点

CRAF

作用机制

CRAF抑制剂(C-Raf激酶抑制剂)

治疗领域

心血管疾病内分泌与代谢疾病眼部疾病+ [1]

在研适应症-

非在研适应症

糖尿病性黄斑水肿黄斑变性

原研机构

Ionis

在研机构-

非在研机构

iCo Therapeutics, Inc.Ionis

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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序列信息

Sequence Code 261211782

关联

2

项与 ICO-007 相关的临床试验

NCT01565148 / Terminated临床2期IIT

A Randomized, Multi-center, Phase II Study of the Safety, Tolerability, and Bioactivity of Repeated Intravitreal Injections of iCo-007 as Monotherapy or in Combination With Ranibizumab or Laser Photocoagulation in the Treatment of Diabetic Macular Edema With Involvement of the FoveAL Center (the iDEAL Study)

To assess the safety of repeated iCo-007 intravitreal injections in treatment of subjects with diabetic macular edema as monotherapy and in combination with ranibizumab or laser photocoagulation
To assess the change in visual acuity and retinal thickness on optical coherence tomography (OCT) from baseline to month 8 and month 12

开始日期2012-02-01

申办/合作机构

The Johns Hopkins University

[+2]

NCT00886808 / Completed临床1期

A Phase I, Open-Label, Dose Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of iCo-007 Intravitreal Injection in Subjects With Diffuse Diabetic Macular Edema

The goal of the study is to evaluate the safety and tolerability of 4 different doses of iCo-007 Intravitreal Injection in patients with diffuse diabetic macular edema.

开始日期2008-02-01

申办/合作机构

iCo Therapeutics, Inc.

100 项与 ICO-007 相关的临床结果

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100 项与 ICO-007 相关的转化医学

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100 项与 ICO-007 相关的专利（医药）

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4

项与 ICO-007 相关的文献（医药）

2011-04-01·Expert Opinion on Therapeutic Targets2区 · 医学

The role of Raf-1 kinase in diabetic retinopathy

2区 · 医学

Review

作者: Renu A Kowluru ; Ghulam Mohammad

Many metabolic pathways, including oxidative stress, PKC and the polyol pathway have been implicated in the development of diabetic retinopathy, but despite extensive research, its pathogenesis remains unclear. Recent studies have shown the role of a low-molecular-weight GTP-binding protein (H-Ras)-mediated signaling pathway in its development. The key effector protein of Ras function is a threonine/serine kinase-Raf kinase, and this kinase is involved in a variety of functions, including the cell cycle and proliferation and apoptosis. In animal models of diabetic retinopathy, Raf kinase is activated in the retina and its microvasculature. Activated Raf kinase is associated with increased apoptosis of retinal capillary cells, the process that precedes the development of retinal histopathology, and inhibition of Raf kinase ameliorates apoptosis. In clinical settings, inhibitors of Raf kinase have shown promising results in cancer treatment, and Raf kinase antisense oligonucleotides, iCo 007, is now in Phase II trial for macular edema, a chronic ocular disease associated with retinal neovascularization. Further elucidating the role of Raf kinase in diabetic retinopathy, and advances in the generation of antisense therapy for chronic diseases, should help test Raf antisense oligonucleotides for the treatment of this blinding complication that diabetic patients fear the most.

2009-07-01·Journal of Diabetes Science and Technology

Antisense Oligonucleotide Therapy in Diabetic Retinopathy

Review

作者: Clement, John G. ; Grillone, Lisa R. ; Hnik, Peter ; Boyer, David S. ; Henry, Scott P. ; Green, Ellen A.

Diabetic retinopathy is one of the leading causes of blindness in the United States and other parts of the world. Historically, laser photocoagulation and vitrectomy surgery have been used for the treatment of diabetic retinopathy, including diabetic macular edema. Both procedures have proven to be useful under certain conditions but have their limitations. New pathways and processes that promote diabetic retinopathy have been identified, and several new therapeutic approaches are under investigation. These new therapies may be beneficial in the treatment of diabetic retinopathy and include antivascular endothelial growth factor agents, corticosteroids, and therapies that may potentially target a number of additional diabetic retinopathy-related factors and processes, including antisense oligonucleotides. Second-generation antisense oligonucleotides, such as iCo-007, may offer a significant advantage in the treatment of diabetic retinopathy by downregulating the signal pathways of multiple growth factors that seem to play a critical role in the process of ocular angiogenesis and vascular leakage. Benefits of such molecules are expected to include the specificity of the kinase target and an extended half-life, resulting in less frequent intravitreal drug administration, resistance to molecule degradation, and a good safety profile.

2006-03-15·International Journal of Cancer1区 · 医学

Comparison of strategies targeting Raf-1 mRNA in ovarian cancer

1区 · 医学

Article

作者: Brett P. Monia ; Fiona McPhillips ; John F. Smyth ; Simon P. Langdon ; Peter Mullen

In this study, we characterize the uptake and specificity of a first-generation Raf-1 antisense oligonucleotide (ASO) (ISIS 5132) and compare it with a second-generation ASO (ISIS 13650) and an RNA interference approach. All three approaches resulted in inhibition of both Raf-1 expression and cellular growth. Specificity of the Raf-1 ASOs was confirmed by comparison with ASOs targeted against another Raf isoform (B-Raf) as well as mismatch sequences. Cellular uptake studies with FAM-labelled ISIS 5132 revealed that whilst the majority of cells treated at a low-intermediate plating density were labelled within 3 hr, cells treated at high density demonstrated neither Raf-1 protein knockout nor significant growth inhibition, following similar treatment. This lack of response at high cell densities was associated with reduced pERK and Raf-1 inhibition. Cell cycle analysis revealed that whilst SKOV-3 cells both accumulated in the S-phase of the cell cycle and showed enhanced annexin V levels, following Raf-1 ASO treatment; these effects were also demonstrated with first-generation but not second-generation mismatch oligonucleotides. Bromodeoxyuridine incorporation analysis suggested that these effects may indeed be partly attributable to sequence nonspecific effects. Finally, the combination of ISIS 5132 with either carboplatin or taxol showed enhanced growth inhibition, supporting the view that such ASOs may have a more effective clinical role when used in combination with cytotoxic agents.

100 项与 ICO-007 相关的药物交易

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