Issue 10, 2012

Optimizing PK properties of cyclic peptides: the effect of side chain substitutions on permeability and clearance

Abstract

A series of cyclic peptides were designed and prepared to investigate the physicochemical properties that affect oral bioavailabilty of this chemotype in rats. In particular, the ionization state of the peptide was examined by the incorporation of naturally occurring amino acid residues that are charged in differing regions of the gut. In addition, data was generated in a variety of in vitro assays and the usefulness of this data in predicting the subsequent oral bioavailability observed in the rat is discussed.

Graphical abstract: Optimizing PK properties of cyclic peptides: the effect of side chain substitutions on permeability and clearance

Supplementary files

Article information

Article type
Concise Article
Submitted
20 Jul 2012
Accepted
16 Aug 2012
First published
31 Aug 2012

Med. Chem. Commun., 2012,3, 1282-1289

Optimizing PK properties of cyclic peptides: the effect of side chain substitutions on permeability and clearance

A. C. Rand, S. S. F. Leung, H. Eng, C. J. Rotter, R. Sharma, A. S. Kalgutkar, Y. Zhang, M. V. Varma, K. A. Farley, B. Khunte, C. Limberakis, D. A. Price, S. Liras, A. M. Mathiowetz, M. P. Jacobson and R. S. Lokey, Med. Chem. Commun., 2012, 3, 1282 DOI: 10.1039/C2MD20203D

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