BC-DXI-32982 is a specific small molecule DX2-KRAS inhibitor that specifically binds to the KRAS-binding region of AIMP2-DX2, inhibits interaction between DX2 and KRAS4B with IC50 of 0.18 uM.
BC-DXI-32982 shows little effect on the PRKACA-PRKAR2A interaction, exhibits inhibitory efficacy on the binding of endogenous DX2 to KRAS with no effect on p14ARF in co-immunoprecipitation.
BC-DXI-32982 (0-10 uM) dose-dependently reduces endogenous KRAS levels and the activities of downstream effectors, p-ERK and p-Akt, in compound treated H460 cells.
BC-DXI-32982 suppresses cell viability in cancer cell lines with high levels of DX2, with no effect on the viability of untransformed MEF cells.
BC-DXI-32982 treatment suppressed phosphorylation of ERK, a KRAS downstream effector, in cancer cell lines regardless of KRAS mutation status, exerts cytotoxic activity by suppressing ERK via KRAS.
BC-DXI-32982 competitively interferes with the interaction between DX2 and KRAS through its binding to the DX2 GST domain, leading to the suppression of KRAS-driven cancer cell growth.
AIMP2-DX2, a variant of the tumor suppressor AIMP2 (aminoacyl-tRNA synthetase-interacting multi-functional protein 2), acts as a cancer-specific regulator of KRAS stability, augmenting KRAS-driven tumorigenesis.