YTHu78 is a KDM5B PROTAC-based degrader. It induces the degradation of KDM5B through the ubiquitin-proteasome system and triggers apoptosis in MV-4-11 and MM.1S cell lines. YTHu78 demonstrates significant antiproliferative activity against various hematologic tumor cell lines and is useful for studying hematological malignancies.

YTHu78 demonstrates antiproliferative activity against MV-4-11, HL60, MM.1S, and OCI-AML3 cells with IC50 values of 1.34 μM, 6.58 μM, 1.03 μM, and 9.07 μM, respectively, over 72 hours. It reduces KDM5B protein levels in MV-4-11 and MM.1S cells through a proteasome-mediated pathway when used at concentrations of 0.03-20 μM for 1-24 hours. Additionally, YTHu78 induces caspase-dependent apoptotic cell death in MV-4-11 and MM.1S cells at 0.03-20 μM over 48 hours. It exhibits negligible antiproliferative effects on primary HUVEC, GM00637 fibroblasts, HaCaT keratinocytes, GES-1, and HEK293 cells, with IC50 values exceeding 20 μM after 72 hours. Limited antiproliferative activity is observed in refractory solid tumors and moderately sensitive solid tumor models, such as HCC, PDAC, gGBM, and TNBC cells, where IC50 values exceed 20 μM, specifically ranging from 6-20 μM for Huh-7, HCC1937, and PANC-1 cells.