Optimizing PK Properties of Cyclic Peptides: the Effect of Side Chain Substitutions on Permeability and Clearance()

Overview

Journal Medchemcomm

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2012 Nov 8

PMID 23133740

Citations 33

Authors

Arthur C Rand

Siegfried S F Leung

Heather Eng

Charles J Rotter

Raman Sharma

Amit S Kalgutkar

Yizhong Zhang

Manthena V Varma

Kathleen A Farley

Bhagyashree Khunte

Chris Limberakis

David A Price

Spiros Liras

Alan M Mathiowetz

Matthew P Jacobson

R Scott Lokey

Affiliations

Soon will be listed here.

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.

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