Abstract
Dipeptidyl peptidase (DPP) IV inhibitors provide a new strategy for the treatment of type 2 diabetes. Human DPP-IV gene was cloned from differentiated Caco-2 cells and expressed in Pichia pastoris. The recombinant enzyme was used in a new system for screening of DPP-IV inhibitors. By high throughput screening, a novel compound (W5188) was identified from 75,000 compounds with an IC(50) of 6.5 microM. This method is highly reproducible and reliable for discovery of DPP-IV inhibitors as shown by Z' value of 0.73 and S/N ratio of 6.89.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Dipeptidyl Peptidase 4 / biosynthesis*
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Dipeptidyl Peptidase 4 / genetics
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Dipeptidyl-Peptidase IV Inhibitors*
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Drug Evaluation, Preclinical / methods
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Enzyme Inhibitors / isolation & purification*
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Enzyme Inhibitors / pharmacology*
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Humans
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Inhibitory Concentration 50
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Pichia / enzymology*
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Pichia / genetics*
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Recombinant Proteins / antagonists & inhibitors
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / genetics
Substances
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Dipeptidyl-Peptidase IV Inhibitors
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Enzyme Inhibitors
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Recombinant Proteins
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DPP4 protein, human
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Dipeptidyl Peptidase 4