Title:
糖尿病性合併症の予防における治療介入のための化合物および方法
Document Type and Number:
Japanese Patent JP4738554
Kind Code:
B2
Abstract:
The present invention is based on the discovery of a metabolic pathway in which a specific kinase converts fructose-lysine into fructose-lysine-3-phosphate in an ATP dependent reaction. Fructose-lysine-3-phosphate (FL3P) is then broken down to form free lysine, inorganic phosphate and 3-deoxyglucosone (3DG), the latter being a reactive protein modifying agent. 3DG can be detoxified by reduction to 3-deoxyfructose (3DF), or it can react with endogenous proteins to form advanced glycation end-product modified proteins (AGE-proteins), which are believed to be a cause of diabetic complications. Disclosed is a class of compounds which inhibit the action of FL3P kinase in the above-mentioned pathway. Also disclosed are therapeutic methods of using such inhibitors to reduce formation of AGE-proteins and thereby lessen, reduce and delay diabetic complications, as well as methods for assessing a diabetic's risk of developing complications and for determining the efficacy of the disclosed inhibitor therapy by measuring the ratio of 3DG to 3DF in a biological sample following an oral dose of a fructose-lysine-containing food product.
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Inventors:
Brown, Truman Earl
Coupler, francis
Shiwar Gold, Benjamin
Ral, Sandeep
Su, Van Inn
Coupler, francis
Shiwar Gold, Benjamin
Ral, Sandeep
Su, Van Inn
Application Number:
JP53323598A
Publication Date:
August 03, 2011
Filing Date:
February 05, 1998
Export Citation:
Assignee:
FOX CHASE CANCER CENTER
International Classes:
A61K31/198; A61K31/13; G01N33/50; A61K31/197; A61K31/275; A61K31/5375; A61K31/7028; A61P3/10; A61P9/10; A61P19/02; A61P25/02; A61P27/02; A61P27/12; A61P43/00; C07C215/14; C07C229/26; C07C255/26; C07H15/04; C07H19/20
Domestic Patent References:
| JP60075435A | ||||
| JP6054699A | ||||
| JP8311470A | ||||
| JP3502454A | ||||
| JP5502870A | ||||
| JP7503713A |
Foreign References:
| WO1996001639A1 | ||||
| CZ235440B6 | ||||
| US2715121 | ||||
| WO1992013992A1 | ||||
| SU1114392A | ||||
| US2870139 |
Other References:
Tetrahedron,(1992),48(2),p.319-24
J.Bacteriology,(1984),vol.158,p.650-8
J.Bacteriology,(1984),vol.158,p.650-8
Attorney, Agent or Firm:
Aoyama Aoi
Mitsuo Tanaka
Mitsuo Tanaka