Fig. 3: Small molecule target tractability assessment.
From: Prioritizing Parkinson’s disease risk genes in genome-wide association loci
Predicted tractability of the 38 prioritized genes that are not already targets of approved or investigational drugs. Data was extracted from the Open Targets platform using GraphQL API queries (https://platform.opentargets.org/) (see Methods). Various forms of evidence that suggest that a target may be tractable are shown on the x-axis, sorted from highest-quality to lowest. Structure with Ligand: a Protein Data Bank co-crystal structure exists for the target and a small molecule. High-Quality Ligand: the target is bound by a ligand that (1) has a property forecast index ≤7, (2) binds ≤2 distinct protein domains and motifs identified by SMART (Simple Modular Architecture Research Tool), and (3) is derived from ≥2 distinct chemical scaffolds. High-Quality Pocket: the target has a DrugEBIlity score ≥0.7. Med-Quality Pocket: the target has a DrugEBIlity score 0–0.7. Druggable Family: the target was reported to be a member of the druggable genome in Finan et al. 90. Light green cells indicate that a given gene is supported by a given form of evidence, while dark green cells indicate an absence of such evidence. For more information on ongoing targeted drug trials for a selection of genes, see Supplementary Table 3.
