KH-103 is a highly potent, catalytically-driven glucocorticoid receptor (GR) PROTAC degrader, demonstrate excellent performance in passively preventing ligand-induced gene expression activation in the absence of partial agonistic transcriptional triggering and crosstalk inhibition.
KH-103 (1 uM) led to efficient and rapid degradation of GR cells within less than an hour in HEK293 cells.
KH-103 shows highly efficient degradation at 10 nM, reaching almost full depletion at 100 nM.
KH-103 shows efficient reversible degradation in various in-vitro models across tissue origins and species.
KH-103 induces nuclear translocation without triggering GR-mediated gene activation.
KH-103 blocks dexamethasone (DEX) effects with increased efficiency compared to other inhibitors.
KH-103 treatment alone has no nonspecific transcriptional effects.
KH-103 effectively depletes GR in the pituitary in vivo and impacts corticosterone levels.