Target identification and the elucidation of a drug’s mechanism of action are critical steps in drug discovery. Different compounds that target the same cancer cell lines generally affect the same biological pathway. Comparing the inhibitory potency of compounds in cancer cell line viability assays can thus reveal differences or similarities in their biochemical mode of action.^1-3

Oncolines® comparative profiling (OncolinesProfiler™) allows for the comparison of a compound’s cellular targeting profile with those of a large, diverse reference library of anti-cancer therapeutics. Recently, this library has been expanded to include almost 250 pre-profiled reference compounds with a wide variety of targets (e.g., RAS, SMARCA2, USP1, SHP2). Most compounds are small-molecule inhibitors, but new therapy classes have been added as well, including protein degraders and antibody–drug conjugates (3 of each in the library).

The expanded library gives additional insights for target identification. For example, the sensitivity profile of the newly included PROTAC degrader DT2216 clusters together with the profiles of the small molecule inhibitors ABT-737 and navitoclax. All three anti-cancer therapeutics target the anti-apoptotic protein BCL-xL. These results indicate that target identification based on comparing sensitivity profiles can be determined independent of therapy class.

To read more about how our expanded reference library of anti-cancer therapeutics is used in the Oncolines® comparative profiling, click below.