Potent, selective and broadly characterized small molecule modulators of protein function (chemical probes) are powerful research reagents. Genetic approaches are used to suppress the expression of the respective gene/protein. However, these methods have some deficiencies in drug discovery. They commonly remove or suppress the entire protein and they are not reversible. Besides, their effects are not instantaneous. Moreover, they not only disrupt the protein, but also the protein interactome around the targeted protein. Thus, selective small molecule modulators can probe the particular function of a targeted domain. And we can study its role in biological processes and in human disease across a wide range of cell and animal models. Furthermore, these probes can also enhance the degradation of the protein(s) they bind to. BAY-474 is a tyrosine-protein kinase c-Met inhibitor and a structural genomics consortium (SGC) epigenetics probe.
BAY-474 is a tyrosine-protein kinase c-Met inhibitor. Meanwhile, BAY-474 is a structural genomics consortium (SGC) epigenetics probe. The ideal chemical probes need to be selective, active in cells and chemically stable. We can use small molecules in a broad panel of assay systems comprising primary cells, tissues and also in vivo models. And it also relevant to other systems not easily amenable even for state-of-the-art genetic target validation methods. The tyrosine kinase mesenchymal-epithelial transition factor (c-Met), encoded by MET proto-oncogene, belongs to a structurally distinct subfamily of receptor tyrosine kinase (RTK). Nonetheless, the c-Met/HGF signaling pathway plays an important role in a diverse array of biological activities. Specifically, c-Met is emerging as an attractive oncology target. All in all, BAY-474 is a tyrosine-protein kinase c-Met inhibitor and an SGC epigenetics probe.
References:
Müller S, et al. Elife. 2018 Apr 20;7. pii: e34311.