SOS1 and cancer: While severalreports have detailed the discovery of small-moleculeagonists of SOS1,26−33 fewer literature reports have described the use of compounds thatdisrupt the SOS1:KRAS complex34−37 or degrade SOS1.38 However,several patent applications have been published describing the useof SOS1 binders to target KRAS mutant cancers.39−54 Early SOS1 binders such as BAY-293 (1)35 and BI-3406 (2)36,37 were discoveredfrom independent high-throughput screening campaigns and serendipitouslyshare the same quinazoline scaffold (Figure 1), similar to many EGFR inhibitors, suchas erlotinib (3, Figure 1).