In silico fragment-based discovery of DPP-IV S1 pocket binders

被引：39

作者：

Rummey, C

Nordhoff, S

Thiemann, M

Metz, G

机构：

[1] Santhera Pharmaceut, Computat Discovery, D-69120 Heidelberg, Germany

[2] Santhera Pharmaceut, Med Chem, D-69120 Heidelberg, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 05期

关键词：

dipeptidyl peptidase-IV inhibitors; molecular anchor; fragment-based discovery; virtual screening; docking;

D O I：

10.1016/j.bmcl.2005.11.038

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Dipeptidyl peptidase IV is a clinically validated target for type-2 diabetes and belongs to a family of peptidases with a quite unique post-proline cleavage specificity. Known inhibitors contain a limited number of molecular anchors occupying the small prototypical S1 pocket. A virtual screening approach for such SI-binding fragments was carried out using FlexX docking to evaluate its potential to confirm known and find novel compounds. Several low molecular weight inhibitors exhibiting activities in the micromolar range could be identified as starting points for structure-based design. (C) 2005 Elsevier Ltd. All rights reserved.

引用

页码：1405 / 1409

页数：5

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