Source:http://linkedlifedata.com/resource/pubmed/id/18223196
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2008-3-18
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| pubmed:abstractText |
BI 1356 [proposed trade name ONDERO; (R)-8-(3-amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione] is a novel dipeptidyl peptidase (DPP)-4 inhibitor under clinical development for the treatment of type 2 diabetes. In this study, we investigated the potency, selectivity, mechanism, and duration of action of BI 1356 in vitro and in vivo and compared it with other DPP-4 inhibitors. BI 1356 inhibited DPP-4 activity in vitro with an IC(50) of approximately 1 nM, compared with sitagliptin (19 nM), alogliptin (24 nM), saxagliptin (50 nM), and vildagliptin (62 nM). BI 1356 was a competitive inhibitor, with a K(i) of 1 nM. The calculated k(off) rate for BI 1356 was 3.0 x 10(-5)/s (versus 2.1 x 10(-4)/s for vildagliptin). BI 1356 was >/=10,000-fold more selective for DPP-4 than DPP-8, DPP-9, amino-peptidases N and P, prolyloligopeptidase, trypsin, plasmin, and thrombin and was 90-fold more selective than for fibroblast activation protein in vitro. In HanWistar rats, the DPP-4 inhibition 24 h after administration of BI 1356 was more profound than with any of the other DPP-4 inhibitors. In C57BL/6J mice and Zucker fatty (fa/fa) rats, the duration of action on glucose tolerance decreased in the order BI 1356 > (sitagliptin/saxagliptin) > vildagliptin. These effects were mediated through control of glucagon-like peptide-1 and insulin. In conclusion, BI 1356 inhibited DPP-4 more effectively than vildagliptin, sitagliptin, saxagliptin, and alogliptin and has the potential to become the first truly once-a-day DPP-4 inhibitor for the treatment of type 2 diabetes.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/DPP4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Dipeptidyl Peptidase 4,
http://linkedlifedata.com/resource/pubmed/chemical/Dipeptidyl-Peptidase IV Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Gelatinases,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoglycemic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Linaclotide Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protease Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Purines,
http://linkedlifedata.com/resource/pubmed/chemical/Quinazolines,
http://linkedlifedata.com/resource/pubmed/chemical/Serine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Markers, Biological,
http://linkedlifedata.com/resource/pubmed/chemical/Xanthines,
http://linkedlifedata.com/resource/pubmed/chemical/fibroblast activation protein alpha
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| pubmed:status |
MEDLINE
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| pubmed:month |
Apr
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| pubmed:issn |
1521-0103
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
325
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
175-82
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| pubmed:dateRevised |
2011-11-17
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| pubmed:meshHeading |
pubmed-meshheading:18223196-Animals,
pubmed-meshheading:18223196-Antigens, Neoplasm,
pubmed-meshheading:18223196-Caco-2 Cells,
pubmed-meshheading:18223196-Diabetes Mellitus, Type 2,
pubmed-meshheading:18223196-Dipeptidyl Peptidase 4,
pubmed-meshheading:18223196-Dipeptidyl-Peptidase IV Inhibitors,
pubmed-meshheading:18223196-Gelatinases,
pubmed-meshheading:18223196-Humans,
pubmed-meshheading:18223196-Hypoglycemic Agents,
pubmed-meshheading:18223196-Inhibitory Concentration 50,
pubmed-meshheading:18223196-Male,
pubmed-meshheading:18223196-Membrane Proteins,
pubmed-meshheading:18223196-Mice,
pubmed-meshheading:18223196-Protease Inhibitors,
pubmed-meshheading:18223196-Purines,
pubmed-meshheading:18223196-Quinazolines,
pubmed-meshheading:18223196-Rats,
pubmed-meshheading:18223196-Rats, Wistar,
pubmed-meshheading:18223196-Rats, Zucker,
pubmed-meshheading:18223196-Serine Endopeptidases,
pubmed-meshheading:18223196-Tumor Markers, Biological,
pubmed-meshheading:18223196-Xanthines
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| pubmed:year |
2008
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| pubmed:articleTitle |
(R)-8-(3-amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione (BI 1356), a novel xanthine-based dipeptidyl peptidase 4 inhibitor, has a superior potency and longer duration of action compared with other dipeptidyl peptidase-4 inhibitors.
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| pubmed:affiliation |
Boehringer Ingelheim Pharma GmbH and Co. KG, Department of Metabolic Diseases Research, Birkendorfer Strasse 65, D-88397 Biberach, Germany. leo.thomas@boehringer-ingelheim.com
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| pubmed:publicationType |
Journal Article,
Comparative Study
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