Ruboxistaurin, a protein kinase C beta inhibitor, as an emerging treatment for diabetes microvascular complications
| Autor: | Moahad Dar, Scott V. Joy, Michael J. Cooney, Ann C Scates, Jason A Goebel, Srilaxmi Bearelly, Christina A Taulien |
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| Rok vydání: | 2005 |
| Předmět: |
medicine.medical_specialty
Indoles MEDLINE Protein Kinase C beta Diabetic angiopathy Pharmacology Ruboxistaurin Maleimides chemistry.chemical_compound Diabetic Neuropathies Diabetes mellitus Internal medicine medicine Animals Humans Pharmacology (medical) Diabetic Nephropathies Enzyme Inhibitors Protein kinase A Protein kinase C Protein Kinase C Clinical Trials as Topic biology Kinase business.industry medicine.disease Endocrinology Treatment Outcome chemistry Enzyme inhibitor biology.protein business Diabetic Angiopathies |
| Zdroj: | The Annals of pharmacotherapy. 39(10) |
| ISSN: | 1060-0280 |
| Popis: | OBJECTIVE: To review current clinical data regarding the pharmacologic actions of ruboxistaurin (LY333531) mesylate, an inhibitor of protein kinase C (PKC) β, and its role to potentially reduce the development and/or the progression of diabetic microvascular complications. DATA SOURCES: Primary literature was obtained via a MEDLINE search (1966–August 2004) and through review of pertinent abstracts and presentations at major medical meetings. STUDY SELECTION AND DATA EXTRACTION: Literature relevant to PKC physiology, the pharmacokinetics of ruboxistaurin, and data evaluating the use of ruboxistaurin in treating diabetic microvascular complications in human and relevant animal models was reviewed. DATA SYNTHESIS: PKC is part of a group of intracellular signaling molecules activated in response to various specific hormonal, neuronal, and growth factor stimuli. Hyperglycemia leads to PKC β 1 and 2 isoform activation, which experimentally has been shown to contribute to the development and progression of diabetic microvascular complications (retinopathy, nephropathy, neuropathy) through various biochemical mechanisms. Animal and/or human studies using ruboxistaurin mesylate, a novel, highly selective inhibitor of PKC β, have shown delay in the progression and, in some cases, reversal of diabetic retinopathy, nephropathy, and neuropathy. CONCLUSIONS: Ruboxistaurin mesylate, by inhibiting excessive activation of certain PKC isoforms, has the potential to reduce the burden of microvascular complications for patients with diabetes. |
| Databáze: | OpenAIRE |
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