SERP
Comments:
LC-04-45 is a potent CRBN-dependent NEK7 glue degrader, with established selectivity in MOLT-4 cells (human T lymphoblast cell line) at short time point (6h).
LC-04-45-induced degradation of NEK7 has been validated in a limited number of cell types: MOLT-4, human PBMC, and human monocyte–derived macrophages, with Dmax > 85% and DC50 < 100 nM across all cell types tested.
Proof of mechanism was obtained using a cellular split nanoluciferase assay: LC-04-45 could show recruitment of SmBiT-CRBN to LgBit-NEK7 in dose dependent manner in HEK293T cells. However, no biophysical assay or structural biology study using purified protein is reported.
Selectivity data obtained in MOLT-4 cells treated with LC-04-45 for 6h appear clean both regarding whole proteomics data and targeted WB on NEK family. Potential caveats include the lack of data at longer timepoints and in different cell types.
Overall, LC-04-45 is a minimally validated chemical probe for NEK7 degradation, that I would recommend to use mostly in complement to more validated NEK7 degrader NK7-902 (https://www.biorxiv.org/content/biorxiv/early/2024/11/08/2024.11.06.622079.full.pdf).
(last updated:
24 Jan 2026 )