YDR1

YDR1 is a research small‑molecule proteolysis-targeting chimera (PROTAC) discovered as a potent, orally bioavailable degrader of the chromatin remodeler SMARCA2 (also known as BRM), developed for preclinical oncology studies. In cellular and in vivo models, YDR1 recruits SMARCA2 to the E3 ligase cereblon, promoting ubiquitination and proteasomal degradation of SMARCA2, leading to growth inhibition of SMARCA4‑mutant and other SMARCA2‑dependent tumor cells.[2] In mice, once‑daily oral dosing of YDR1 produces dose‑dependent degradation of SMARCA2 in multiple tissues and xenograft tumors with favorable tolerability, and shows synergistic antitumor activity in combination with the KRAS G12C inhibitor sotorasib in SMARCA4/KRAS‑mutant models.[2]