Compound class:
Synthetic organic
Comment: SGI-1776-VHL-02 is a pan-PIM kinase PROTAC degrader [1]. The PIM-targeting warhead is the inhibitor SGI-1776, and this in linked to a VHL-binding ligand to engage the von Hippel-Lindau (VHL) Cullin 2-Ring ubiquitin ligase, and direct the PIM protein targets for ubiquitin mediated degradation in the proteasome. SGI-1776-VHL-02 degrades PIM1 with no "hook-effect" at high doses.
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Bioactivity Comments |
SGI-1776-VHL-02 promotes degradation of all 3 PIM isoforms in vitro [1]. 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). |