DS-6051b

DS-6051b is a new-generation selective inhibitor of ROS1/NTRK including ROS1, NTRK1, NTRK2 and NTRK3 with IC50 of 0.207 nM,0.622 nM,2.28 nM and 0.980 nM, respectively.DS-6051b inhibited the growth of the ROS1 fusion-positive HCC78 cancer cell line and the CD74-ROS1 overexpressed Ba/F3 cells. DS-6051b potently inhibited autophosphorylation of ROS1 in the SLC34A2-ROS1 harboring HCC78 cells and CD74-ROS1-expressed Ba/F3 cells at approximately single-digit to double-digit nanomolar concentration.DS-6051b induced tumor shrinkage at a ≥50mg/kg in vivo experiments using the KM12-bearing mouse xenograft model or higher treatment dose without significant body weight loss.