Compound class:
Synthetic organic
Comment: PIM447-VHL-01 is a PIM1-selective PROTAC degrader [1]. The PIM-targeting warhead is the inhibitor PIM447, and this is linked to a VHL-binding ligand to engage the von Hippel-Lindau (VHL) Cullin 2-Ring ubiquitin ligase, and direct the PIM protein target for ubiquitin mediated degradation in the proteasome. PIM447-VHL-01 degrades PIM1 with no "hook-effect" at high doses.
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Bioactivity Comments |
In prostate cancer cell lines degradation of PIM kinases was found to more effectively induce apoptosis than inhibition of catalytic activity (i.e. kinase inhibitor alone) [1]. |