Peptides fill a significant physicochemical and therapeutic gap between small molecules and monoclonal antibodies which is the main reason they have recently regained favor within drug discovery community. As the interest in peptides grows, it is important to remember that in order to become a drug a molecule must possess many properties beyond modulation of a challenging target. Peptides fell from favor within the pharmaceutical industry largely for pharmacokinetic reasons, including rapid proteolytic cleavage, limited cell permeability, and the potential for exciting a serious immune response. Thus, in order for peptides to truly regain favor within drug discovery groups, these pharmacokinetic (ADME/Tox) problems must be solved. Fortunately, there is significantly more information available to the peptide community than a decade or two ago. Given the difficulty of simultaneously solving a number of ADME/Tox issues, while maintaining a complex pharmacological activity, it is crucial that researchers integrate all this information into their drug discovery programs as early as possible. Here we describe our progress towards developing computational tools within our peptide drug discovery platform CMDInventus to first understand peptide ADME/Tox problems and then to aid researchers in solving them. In particular, we focus attention on new and encouraging results obtained for therapeutic peptide protease stability, cell permeability, and immunogenicity modeling and prediction using an approach that combines the strengths of both cheminformatics and bioinformatics methods.

Understanding and solving ADME/Tox issues in peptide-based drug discovery using novel computation tools in CMDInventus

250th National Meeting (2015)

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