PROTAC SOS1 degrader-1

PROTAC SOS1 degrader-1 (Compound 9d) (contact time: 120 s, dissociation time: 240 s) forms a ternary complex with highly positive cooperativity with SOS1 and VCB proteins, with a cooperativity factor of 15.1, a binary K_D value of 56.0 nM, and a ternary K_D value of 3.7 nM^[1].
PROTAC SOS1 degrader-1 (0-2000 nM; 24 h) induces dose-dependent degradation of SOS1 in NCI-H358 cells, with a DC₅₀ of 98.4 nM, and achieves a degradation rate of 92.5% after treatment at 1 μM for 24 h^[1].
PROTAC SOS1 degrader-1 (1 μM; 1-24 h) induces time-dependent degradation of SOS1 in NCI-H358 cells (peaking at 24 h) and AsPC-1 cells (peaking at 16 h)^[1].
PROTAC SOS1 degrader-1 (7 days) inhibits 3D proliferation of human cancer cells harboring KRAS^G12C, KRAS^G12D, KRAS^G12V, and KRAS^G12S mutations, with IC₅₀ values ranging from 0.115 to 0.525 μM after 7 days of treatment, but exerts no inhibitory effect on the proliferation of CAL-62 or 293T cells^[1].
PROTAC SOS1 degrader-1 (1 μM; 1-24 h) transiently increases pERK levels in NCI-H358 cells, followed by inhibition of ERK phosphorylation; it exhibits an IC₅₀ of 72.3 nM for pERK inhibition after 24 hours of treatment^[1].
Treatment with PROTAC SOS1 degrader-1 for 24 h reduces the level of activated KRAS-GTP in NCI-H358 cells in a dose-dependent manner^[1].

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