Comparing structural and transcriptional drug networks reveals signatures of drug activity and toxicity in transcriptional responses

The structural network among 5452 compounds. The network is partitioned into communities (groups of highly interconnected nodes) and rich-clubs (groups of communities) sharing common chemical structures and enriched for drugs with similar Mode of Action. Examples of three Rich Clubs are shown. a The steroids rich-club (1: testosterone scaffold, 2: estradiol scaffold, 3: cortisone scaffold, 4: progesterone scaffold, 5 and 6: mixed steroids); b The antibiotics rich-club (1 and 2: tetracycline scaffold, 3: cephalosporin scaffold, 4: penicillin scaffold); and c The CNS-acting drug rich-club (1 and 2: phenothiazine scaffold, 3–6: various tricyclic antidepressant scaffolds