P1D-34 is a first-in-class, potent and covalent PROTAC degrader of Pin1 with DC50 value of 177 nM in MV-4-11 cells, Dmax of 95%.
P1D-34 coupled the covalent Pin1 inhibitor Sulfopin to a cereblon ligand.
P1D-34 induces cell cycle arrest and apoptosis in AML cells, exhibits cell growth inhibitory activities with IC50 of 2-8 uM in a panel of AML cell lines: MV-4-11, MOLM-13, HL-60, THP-1, Kasumi-1, BDCM and OCI-AML3.
P1D-34 sensitizes ABT-199 against ABT-199-resistant AML cell lines, induces DNA damage and apoptosis by releasing ROS generation, and sensitizes 2-DG by down-regulating UPR pathways.
