< Back to previous page


Active Center-Asisted Selection and Assembly (ACASA): a bottom-up approach to druglike protease inhibitors using caspase 4 as a model target.

This proposal aims at developing an innovative, robust and time/cost-effective methodology with general applicability in the field of protease inhibitor research. As such, it projects the production of target compounds with a non-peptidic architecture consisting of a central, rigid scaffold decorated with substituents that are accomodated in the S- and/or S'-pockets of a target protease. The proposal's approach differs fundamentally from existing methodologies in its systematic investigation and implementation of target-assisted selection and assembly strategies.The validity of the basic inceptions underlying the approach will be assessed by applying it for the production of druglike inhibitors for the cysteine protease caspase 4. Caspase 4 is a so-called inflammatory caspase. This group of enzymes is currently the subject of intense research that tries to map their functions and its involvement in a whole series of pathologies. To date, no inhibitors that are selective for this enzyme with respect to the other caspases, have been described. Evidently however the availability of such compounds would be highly desirable, both for applications as a research tool or as potential therapeutics.
Date:1 Oct 2012 →  30 Sep 2016
Disciplines:Organic chemistry, Biomarker discovery and evaluation, Drug discovery and development, Medicinal products, Pharmaceutics, Pharmacognosy and phytochemistry, Pharmacology, Pharmacotherapy, Toxicology and toxinology, Other pharmaceutical sciences