The G protein-coupled receptor (GPCR) family is among the most druggable families in the human proteome.
Also represented are several "druggable" classes [74], like kinases (e.g. HIPK1, MAPKAPK2, MELK, RPS6KB2, PAK1, TAOK1, PIP4K2B, RPS6KB1, TLK2, MAP3K3), phosphatases (e.g. PTPN1), proteases (e.g. ADAM9), G protein-coupled receptors (e.g. GPRC5C) and ion channels (e.g. VDAC2).
Once a highly ranked druggable target is identified, DrugFEATURE searches for the most druggable microenvironment by counting the frequency of a microenvironment matched in druggable subsites.
Seven microenvironments are frequently (>10%) being labeled as a part of a druggable subsite, and these are the most druggable microenvironments in the query site.
Instead, it looks for local similarity and identifies a set of most druggable microenvironments that combine to create potentially novel recognition units for particular chemical groups.
Studies have shown that EGFR mutations are the most "druggable" oncogene driver mutations, with deletion of exon 19 and L858R mutation (exon-21) being the most common EGFR mutations associated with good TKI response in NSCLC patients [ 5, 6].
First, GPCRs locate on the plasma membrane and their functions are modulated by extracellular molecules, placing them among the most druggable targets: highly accessible to drugs and the functions are modulated by small molecules.
Kinases and phosphatases are a druggable class of proteins critically involved in regulation of signal pathways of eukaryotic cells.
With this strategy not only we ensured that this druggable class of proteins was the major focus of the screening but also we bias it representation in the final results diminishing the probability of off-target proteins.
HDAC-mediated histone deacetylation is a key epigenetic modification that has attracted enormous attention since histone deacetylases emerged as a druggable class of enzymes [ 21].
