doi.org
Target Engagement Assays in Early Drug Discovery
In target-based drug discovery, quantification of target engagement is required to build structure–activity relationships and develop a potent clinical candidate. Target engagement data also provides evidence of a drug’s mechanism of action (MoA) which although is not required for approval, can increase the chance of a successful clinical outcome. Consequently, a plethora of assays has been developed to provide information about target engagement on isolated proteins and in cells. These techniques monitor changes in stability, structure, optical properties or mass difference between proteins and their complexes with ligands. They also provide characterization of the compound with thermodynamic, kinetic and structural binding parameters. The diversity of approaches reflects the challenges faced when drugging different protein classes, with each method having advantages, trade-offs and target specificity.
![Comic. Dimensional Lumber Tape Measure. [mockup of “2x4” piece of wood showing the dimensions as 1½“ by 3 ½“] Dimensional lumber sizes are tricky. A “2x4” is actually 1½“ by 3 ½“, and a “1x8” is ¾“ by 7⅛“. [two tape measures: one is labeled 12’, the other 12’*] If you know someone into carpentry or woodworking, get them our *dimensional lumber tape measure*. [A “normal tape measure” with even increments and a “dimensional lumber tape measure” with increments at different lengths for each inch] *Don’t tell them you got it*—just leave it in their toolbox. They’ll appreciate the surprise when all their measurements work out!](https://cdn.bsky.app/img/feed_thumbnail/plain/did:plc:cz73r7iyiqn26upot4jtjdhk/bafkreigv4ewit5j2o4jyy5twrm5kz4bv5iq7ve72fg7b6dncksdluntfnq)
![[Person with ponytail wearing lab coat hands balloon to another person in front of a springboard, a magnet hanging from above, and then a target] PERSON WITH PONYTAIL to Person 2: Rub this balloon against your head, then go jump past that magnet toward the target on the wall. [caption] Before the bathroom scale was invented, the only way to weigh people was mass spectrometry.](https://cdn.bsky.app/img/feed_thumbnail/plain/did:plc:cz73r7iyiqn26upot4jtjdhk/bafkreid7lnvd7afmasx3nxi6anxmyhbatpaw54za3kiw3eaoclrf722faq)
