Concentration‐dependent plasma protein binding of the novel dipeptidyl peptidase 4 inhibitor BI 1356 due to saturable binding to its target in plasma of mice, rats and humans

Objectives The purpose of this study was to characterise the plasma protein binding of BI 1356.

[1]  Vincent S Stoll,et al.  Crystal structures of DPP-IV (CD26) from rat kidney exhibit flexible accommodation of peptidase-selective inhibitors. , 2006, Biochemistry.

[2]  B. Ahrén.  Enhancement or prolongation of GLP-1 activity as a strategy for treatment of type 2 diabetes , 2004 .

[3]  G. McCaughan,et al.  CD26: A Multifunctional Integral Membrane and Secreted Protein of Activated Lymphocytes , 2001, Scandinavian journal of immunology.

[4]  Sven Branner,et al.  Crystal structure of human dipeptidyl peptidase IV/CD26 in complex with a substrate analog , 2003, Nature Structural Biology.

[5]  M. Tadayyon,et al.  (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 , 2008, Journal of Pharmacology and Experimental Therapeutics.

[6]  E. U. Graefe-Mody,et al.  Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Oral Doses of BI 1356, an Inhibitor of Dipeptidyl Peptidase 4, in Healthy Male Volunteers , 2008, Journal of clinical pharmacology.

[7]  Xin Chen,et al.  One Site Mutation Disrupts Dimer Formation in Human DPP-IV Proteins* , 2004, Journal of Biological Chemistry.

[8]  R. Mentlein.  Cell-Surface Peptidases , 2004, International Review of Cytology.

[9]  T. Rosenthal,et al.  Clinical Pharmacokinetics of Ramipril , 1994, Clinical pharmacokinetics.

[10]  B. Sébille,et al.  The binding of drugs to blood plasma macromolecules: recent advances and therapeutic significance , 1984 .

[11]  B. Pauli,et al.  Is the Fischer 344/CRJ rat a protein-knock-out model for dipeptidyl peptidase IV-mediated lung metastasis of breast cancer? , 1999, Clinical & Experimental Metastasis.

[12]  Y. Watanabe,et al.  Deficiency of membrane-bound dipeptidyl aminopeptidase IV in a certain rat strain , 1987, Experientia.

[13]  O. Cordero,et al.  Preoperative serum CD26 levels: diagnostic efficiency and predictive value for colorectal cancer , 2000, British Journal of Cancer.

[14]  Y. S. Kim,et al.  Biosynthesis and degradation of altered immature forms of intestinal dipeptidyl peptidase IV in a rat strain lacking the enzyme. , 1992, The Journal of biological chemistry.

[15]  H. Nar,et al.  8-(3-(R)-aminopiperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydropurine-2,6-dione (BI 1356), a highly potent, selective, long-acting, and orally bioavailable DPP-4 inhibitor for the treatment of type 2 diabetes. , 2007, Journal of medicinal chemistry.

[16]  S. Pizzo,et al.  Characterization of human serum dipeptidyl peptidase IV (CD26) and analysis of its autoantibodies in patients with rheumatoid arthritis and other autoimmune diseases. , 2001, Clinical and experimental rheumatology.

[17]  Y. Misumi,et al.  An active-site mutation (Gly633-->Arg) of dipeptidyl peptidase IV causes its retention and rapid degradation in the endoplasmic reticulum. , 1992, Biochemistry.

[18]  S. Bloom,et al.  Incretins and other peptides in the treatment of diabetes , 2007, Diabetic medicine : a journal of the British Diabetic Association.

[19]  D. Marguet,et al.  Enhanced insulin secretion and improved glucose tolerance in mice lacking CD26. , 2000, Proceedings of the National Academy of Sciences of the United States of America.