Low-pg/mL quantification of TL 13-112, a proteolysis targeting chimera (PROTAC) in rat plasma

The interest in targeted protein degradation shifted from academia to industry after the therapeutic potential of a PROTAC was documented in 2001. PROTACs have emerged as a therapeutic modality and several candidates have moved into clinical trials. The potential of PROTACs is coded in its structure. A linker connects a protein of interest (POI) binding moiety to a ubiquitin E3 ligase recognition moiety. In the technical note, SCIEX demonstrates a highly sensitive, robust, and rapid workflow to quantify TL 13-112, a selective anaplastic lymphoma kinase (ALK) degrader, and its inactive control, TL 13-110, in rat plasma using the SCIEX 7500 triple quadrupole mass spectrometer. The front-end enhancements of the system facilitated greater sensitivity, which improved overall ion generation, capture and transmission.