MRGX2 receptor antagonists
Prof. Christa E. Müller, Rheinische Friedrich-Wilhelms University Bonn; Dr Steven De Jonghe, KU Leuven; Dr Piet Herdewyn, KU Leuven; Dr Wessam Alnouri, Rheinische Friedrich-Wilhelms University Bonn; Yvonne Riedel, Rheinische Friedrich-Wilhelms University Bonn; Dr Dominik Thimm, Rheinische Friedrich-Wilhelms University Bonn; Daniel Marx, Rheinische Friedrich-Wilhelms University Bonn; Dr Vigneshwaran Namasivayam, Rheinische Friedrich-Wilhelms University Bonn; Susanne Gattner, Rheinische Friedrich-Wilhelms University Bonn; Piotr Leonczak, KU Leuven; Sven Verdonck, KU Leuven
G protein-coupled receptors (GPCRs) are the largest group of membrane receptor proteins and represent the most successful targets of drug therapy. The MRGPRX (mas-related G protein-coupled receptor X) subfamily is only expressed in primates including humans and belongs to the group of orphan receptors, for which the cognate agonists are unknown. The MRGX2 receptor subtype exhibits unique features that distinguishes it from other GPCRs. It is involved in mast cell degranulation, nociception and itching, and represents a fundamentally new drug target. Relating thereto, the development of potent and selective MRGPRX receptor antagonists is a basic need for the design of anti-nociceptive or anti-pruritic drugs or for the prevention or treatment of other diseases like inflammatory diseases, non-allergic hypersensitivity reactions, fibrosis (lung, liver etc.) and neuropathic pain.
The invention relates to a method for preventing or treating a disease or disorder that is associated with the MRGX2 receptor. The technology embodies potent and selective MRGX2 receptor antagonists, including G protein-biased antagonists, that may especially be used for treating pain conditions, such as neuropathic or chronic pain and itch, and reactions, e.g. of the skin, in which mast cells are involved. Many related illnesses may be included, e.g. stress-associated syndromes or asthma, urticaria, skin inflammation, dry skin, psoriasis etc.. Given the newly elucidated role of this receptor in chronic urticaria and pseudoallergic reactions, the antagonists have a high potential to be used for target validation, for preclinical studies, and for their clinical development of novel drugs.
PROvendis is offering licenses for the invention to interested companies on behalf of the Universities of Bonn and Leuven. There is also the possibility of collaboration with the inventors.
In vitro characterization in recombinant cells and on human mast cells.
A US Priority patent application has been filed.
Dissertation M. Wessam Alnouri (2016), later published
Further publications in preparation.