| Description: | (R)-BI-2852 is the inactive isomer of BI-2852 (HY-126247), and can be used as an experimental control. BI-2852 is a KRAS inhibitor for the switch I/II pocket (SI/II-pocket) by structure-based agent design with nanomolar affinity. BI-2852 is mechanistically distinct from covalent KRASG12C inhibitor (binds to switch II pocket) and binds ten-fold more strongly to active KRASG12D versus KRASwt (740 nM vs 7.5 ?M). BI-2852 blocks GEF, GAP, and effector interactions with KRAS, leading to inhibition of downstream signaling and an antiproliferative effect in KRAS mutant cells. |
