| Literature DB >> 12015594 |
M B Pepys1, J Herbert, W L Hutchinson, G A Tennent, H J Lachmann, J R Gallimore, L B Lovat, T Bartfai, A Alanine, C Hertel, T Hoffmann, R Jakob-Roetne, R D Norcross, J A Kemp, K Yamamura, M Suzuki, G W Taylor, S Murray, D Thompson, A Purvis, S Kolstoe, S P Wood, P N Hawkins.
Abstract
The normal plasma protein serum amyloid P component (SAP) binds to fibrils in all types of amyloid deposits, and contributes to the pathogenesis of amyloidosis. In order to intervene in this process we have developed a drug, R-1-[6-[R-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid, that is a competitive inhibitor of SAP binding to amyloid fibrils. This palindromic compound also crosslinks and dimerizes SAP molecules, leading to their very rapid clearance by the liver, and thus produces a marked depletion of circulating human SAP. This mechanism of drug action potently removes SAP from human amyloid deposits in the tissues and may provide a new therapeutic approach to both systemic amyloidosis and diseases associated with local amyloid, including Alzheimer's disease and type 2 diabetes.Entities:
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Year: 2002 PMID： 12015594 DOI： 10.1038/417254a
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 49.962