Drug Designing: Open Access
Open Access

CREB binding protein (CBP) inhibition and target engagement

International Conference and Expo on Drug Discovery & Designing

August 11-13, 2015 Frankfurt, Germany

Eugene Piatnitski Chekler

Posters-Accepted Abstracts: Drug Des

Abstract :

Fully profiled chemical probes are essential to support the unbiased interpretation of biological experiments necessary for rigorous
preclinical target validation. We believe that by developing a chemical probe tool kit, chemical biology can have a more central role
in identifying targets of potential relevance to disease, avoiding many of the biases that complicate target validation. A development of
CREB Binding Protein (CREBBP) selective chemical probe to elucidate biology associated with this bromodomain epigenetic target
is presented. Chemical probe optimization is a strategic balance between physiochemical properties and chemistry, to identify high
affinity binders that are functionally active and selective, with good permeability properties. The selectivity of the chemical probe
against other bromodomain family members was investigated using biochemical and biophysical assays. To address the selectivity
issue with BRD4, X-ray crystal structures of the probe candidates bound to CREBBP and BRD4 were used to guide the design. The
chemical probes were useful in studies aimed at validating CREBBP as a therapeutic target and for establishing its biological role.