Recipient: University of Cologne
Funding: Go-Bio initial (01/10/2022 to 30/09/2023, EUR 119,947.27)

Project description:

Necrosis is the death of cells in a living organism. This can be due to a lack of oxygen and nutrients resulting from a circulatory disorder, infections and external physical or toxic influences. Necroptosis is a programmed form of necrosis that is similar to it in its external form, but in contrast to it is started or controlled by a large number of chained signal steps in the cell, so-called signalling cascades.
Infections, liver diseases, disorders of the nervous system, cardiovascular diseases, cancers and other forms of disease are directly associated with necroptosis. At present there is no specific possibility of intervention in the course of the disease. A targeted inhibition of the protein mixed lineage kinase domain-like (MLKL) would be a possibility, as it is exclusively involved in the process of necroptosis. 
This is what the NEKIN project is working on and is investigating small molecules for their inhibitory activity with respect to MLKL. For this purpose a structural change in the protein MLKL is to be induced, whereby the function of the protein is blocked. As part of the exploratory phase a multidisciplinary scientific team will be established for the development of drug candidates. The concept is to be additionally extended to other molecules and a detailed development and implementation plan is to be drawn up.
In the future new drugs are to be developed for the treatment of various diseases associated with necroptosis. Here, the MLKL inhibitors would represent drug representatives of the first in their class (first-in-class), which gives them an enhanced innovative character.