Q1 · CROSS-FIELD
ArticleOA
Author: Mancias, Joseph D ; Robichaud, Amanda ; Seong, Bo Kyung A ; Mohardt, Mikaela L ; Ferguson, Fleur M ; Nabet, Behnam ; Stegmaier, Kimberly ; Conway, Amy S ; Leggett, Alan L ; Kuljanin, Miljan ; Bradner, James E ; Gray, Nathanael S ; Buckley, Dennis L
Abstract:Chemical biology strategies for directly perturbing protein homeostasis including the degradation tag (dTAG) system provide temporal advantages over genetic approaches and improved selectivity over small molecule inhibitors. We describe dTAGV-1, an exclusively selective VHL-recruiting dTAG molecule, to rapidly degrade FKBP12F36V-tagged proteins. dTAGV-1 overcomes a limitation of previously reported CRBN-recruiting dTAG molecules to degrade recalcitrant oncogenes, supports combination degrader studies and facilitates investigations of protein function in cells and mice.