Relating network connectivity to consensus drug mechanism | Notably, all the connected ligands within the subnetwork shared a similar microtubule destabilization effect. |
Supporting Information | Identification of a compound subnetwork with a consensus tubulin destabilizing effect, related to Fig. |
Supporting Information | (A) Mapping of tubulin polymerization activity onto the mitotic compound set CSN identified a compound subnetwork with a consensus tubulin destabilization effect. |
Supporting Information | (B) Tubulin polymerization kinetics for 7 novel tubulin destabilizers (6—12), based on a phenyl-sulfanyl-thiazol-acetamide scaffold, using an in-vitro tubulin polymerization assay. |
Target validation of mitotic compounds from CSNAP predictions | To test CSNAP’s prediction that 51 of the 212 mitotic compounds were targeting microtubules, we reacquired all 212 compounds and tested their ability to perturb micro-tubule polymerization (stabilize or destabilize microtubules) in an in-vitro microtubule polymerization assay at 50uM concentration (Fig. |