Feasibility phase

Proteins are the main target of drugs at the molecular level. Unfortunately, this therapeutic strategy is currently only applicable to less than 15 percent of human proteins, as the remaining 85 percent do not have a suitable binding pocket for conventional active substances. The aim of MoProX is to develop these target proteins, which were previously considered unaddressable, based on the concept of molecularly induced spatial proximity. The molecular “gluing” of two proteins by means of so-called “molecular glues” causes them to lose their function. This makes many of these previously inaccessible target proteins accessible. This opens the door to completely new therapeutic approaches.

Making the “Undruggable” Druggable with Molecular Glues

In many cancers, the defective proteins are often known. Unfortunately, these are often among the 85 percent of proteins without a suitable binding pocket for classical drugs. However, these cancers can potentially be treated with molecular glues. The MoProX-2 project team has built a platform with a library of potential drug candidates that can be used to efficiently identify and optimise these molecular glues. Several new drug candidates for different types of cancer are therefore to be developed over the course of the project.

Conceptual phase

The MoProX project addresses the problem that numerous disease-relevant proteins do not have a binding pocket for traditional, small molecule drugs and thus cannot be used for therapeutic approaches.

The core idea of MoProX is to develop new drugs, so-called molecular glues, that can bind to two proteins at the same time in a cooperative manner. Initially, the active ingredient binds highly potently to an adapter protein. The adapter protein-drug complex can now bind to a specific target protein through a much larger contact area, which does not have a classic binding pocket for small active substances. The target protein is inhibited by the binding, which achieves a therapeutic effect.

For the MoProX project applicants will be provided with an extensive, self-developed drug library for two types of adapter proteins as well as specific screening technologies. The molecular glues approach allows access to a completely new group of drugs and thus new therapeutic approaches for diseases that were previously difficult to treat but occur widely, such as various types of cancer, diabetes, chronic pain or depression. In the upcoming exploratory phase a concept for the best possible utilisation of the molecular glues is to be developed. To this end an IP strategy will be developed, the market and competition will be analysed and an implementation plan for the subsequent feasibility phase will be drawn up.

Detailed information about all phase 4 projects