LHF418

LHF418 (10 nM-10 μM; 24 h) degrades SOS1 in a dose-dependent manner in A549 cells, with a DC₅₀ of 209.4 nM and a D_max of > 80%; at high concentrations of 20 μM and 30 μM, a hook effect occurs, and SOS1 degradation is incomplete^[1].
LHF418 (3 μM; 0-72 h) reduces SOS1 protein levels in A549 cells in a time-dependent manner, with a T_1/2 of 22.51 h fitted to the time curve; SOS1 levels decrease significantly at 24 h and continue to decline for at least 72 h^[1].
LHF418 (10 nM-10 μM; 24 h) induces SOS1 degradation in KRAS^G12D-bearing HPAF-II cells, with a DC₅₀ of 353.9 nM^[1].
LHF418 (10 nM-10 μM; 24 h) induces SOS1 degradation in MIA-PACA2 cells carrying KRAS^G12C, with a DC₅₀ of 539.7 nM^[1].
LHF418 produces the highest maximum luminescence signal among the compared PROTACs in the AlphaScreen assay containing GST-SOS1 (100 nM) and His-CRBN (10 nM), which supports the formation of a strong SOS1-PROTAC-CRBN ternary complex^[1].
SOS1 degradation induced by LHF418 (1 μM; 24 h) in A549 cells is blocked by the SOS1 warhead BI3406 (HY-125817) (10 μM; 1 h pre-exposure) or the CRBN ligand Lenalidomide (HY-A0003) (10 μM; 1 h pre-exposure)^[1].
In A549 cells, the SOS1 degradation induced by LHF418 (1 μM; 24 h) is completely blocked by MG132 (HY-13259) (1 μM; 1 h pre-exposure) or MLN4924 (HY-70062) (0.5 μM; 1 h pre-exposure), whereas Bafilomycin (1 μM; 1 h pre-exposure) fails to restore SOS1 levels. These findings support that SOS1 degradation depends on the CRBN/ubiquitin-proteasome system rather than the lysosomal autophagy pathway^[1].
LHF418 (10 nM-10 μM; 24 h) reduces SOS1 protein levels in A549 cells, but does not decrease SOS2 or GSPT1 protein levels even at the highest concentration of 10 μM^[1].
LHF418 (10 nM-10 μM; 24 h; EGF 5 ng/mL, 1 h) inhibits EGF-induced ERK1/2 phosphorylation concomitant with a reduction in SOS1 levels in serum-starved A549 cells^[1].
LHF418 (300 nM-30 μM; 14 days) inhibits the colony formation of MIA-PACA2 cells, and colony formation further decreases with increasing concentration^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.