Development of Novel p16INK4a Mimetics as Anticancer Therapy
Abstract
Mesothelioma therapy is a highly fatal disease that has poorly effective therapy with dose-limiting side-effects. Low expression of the CDK4/CDK6 inhibitor p16INK4a has been demonstrated in up to 90% of mesothelioma tumors. The objective of this application as a next step in the pursuit of this long term goal is to identify stabilized peptides that will mimic the interaction between p16INK4a and CDK4/6. The central hypothesis of this proposal is that protein-protein interactions can be replicated or disrupted by stabilized peptides that have been identified via the identification of pharmacophores of small peptides that interact with CDK4/6. The specific aims are as follows. (1) Determine structure-function relationships of overlapping peptides derived from p16INK4a that inhibit the activity of CDK4/6 and identify stabilized peptides that inhibit CDK4/6. (2) In vitro functional studies will be used to evaluate bioactivities of stabilized peptides. (3) In vitro ADME studies studies to evaluate the cell permeability, delivery, and efficacy of stabilized peptides.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2014
- Accession Number
- ADA615123
Entities
People
- Mark Klein