Here we show that both compounds 24 and 26, hereafter referred to as KH1 and KH2 respectively, are fast, low to sub-nanomolar degraders of both GSK3 isoforms, with impact on CNS relevant GSK3 substrates in cells. In addition, they demonstrate very high levels of proteome-wide specificity, qualifying them as cellular chemical probe quality GSK3 degrader molecules identified from a single D2B screen.