YJ1206 is a selective, orally bioavailable CDK12/13 PROTAC degrader, shows potent degradation effects and inhibits VCaP cell viability (IC50=12.5 nM).
YJ1206 demonstrated the best PK properties, with a bioavailability over 39% by oral gavage.
YJ1206 treatment significantly increased the transcripts at the TSSs in VCaP cells, while a distinct reduction toward the TESs of the long genes ATM and ATR was observed in a time-dependent manner.
YJ1206 combined with AKT inhibitors (uprosertib, capivasertib, and MK2206) triggers a synergistic effect in vitro, The combination regimen of CDK12/13 degraders with AKT inhibitors suppresses tumor growth in vivo.
