Fig. 6

Construction of a drug screening platform capable of exploring inhibitory effects selective on KRAS (G13C) iPSC-HPCs. a A schematic representation of a drug screening system utilizing iPSC-HPCs. An isogenic pair of control (WT) and mutant (G13C) iPSC-HPCs were directly sorted into 96-well plates (n = 3 as technical replicates) and cultured for one week under the standard (unless stated) condition with or without the presence of candidate compounds. Cell viability was quantified by assessing intracellular ATP levels (ic ATP) with a luminescence measurement system. b Dose–response plots assessing growth inhibitory effects of a single reagent on either control (C2-1, blue) or KRAS-mutant (R2-1, orange) HPCs. The percent growth was estimated relative to the control values (DMSO). Calculated IC₅₀ values are indicated. Shown are the examples of plots exhibiting a visible selective activity (Trametinib and Navitoclax), only modest selectivity (Palbociclib), and no such selectivity (WP1066). c Summary of the results obtained with candidate compounds tested in the established screening platform. The name of each compound is shown, along with its target (Mechanism) and the estimated values of IC₅₀. The compounds showing reduced IC₅₀ values for mutant HPCs (< 0.5 of the control IC₅₀) are considered selective and thus a "Hit" compound (underlined)