TYMJ-01

TYMJ-01 is a fluorescent probe and an eEF2K degrader. It induces specific, dose-dependent degradation of eEF2K through the ubiquitin-proteasome pathway with a DC50 of 82 nM. TYMJ-01 inhibits the proliferation, migration, and invasion of triple-negative breast cancer cells and enables dynamic fluorescent imaging of eEF2K degradation within these cells. Additionally, it enhances the antitumor activity of Paclitaxel. TYMJ-01 is applicable for research on triple-negative breast cancer.

eEF2K:82 nM (DC50)

TYMJ-01 facilitates real-time visualization of the degradation process of eEF2K in immobilized MDA-MB-231 cells at a concentration of 500 nM over a period of 3 to 48 hours, showing decreased fluorescence intensity correlating with incubation time and colocalization with eEF2K in the nucleus. In live MDA-MB-231 cells, TYMJ-01 at 10 μM for 1 to 48 hours allows for the real-time observation of eEF2K degradation, with fluorescence peaking at 6 hours before diminishing without causing cell damage. TYMJ-01 at 500 nM for 24 hours exhibits very low cytotoxicity alone but significantly enhances the antitumor activity of Paclitaxel in MDA-MB-231 cells. It inhibits cell proliferation at concentrations of 0.2 to 1.0 μM over 24 hours and induces G1 phase cell cycle arrest by downregulating key cell cycle regulators when applied at 0.2 to 1.0 μM for 48 hours. Additionally, TYMJ-01 at 200 nM for 48 hours suppresses cell migration by downregulating critical migration-related regulatory factors. Lastly, within a 24-hour timeframe, TYMJ-01 in doses ranging from 4.12 to 1000 nM can dose-dependently downregulate proliferation, survival, and migration-related proteins c-Myc, Bcl-2, and N-cadherin in MDA-MB-231 cells.