In Table 3 (pages 7-9), which lists “Protein degraders in and approaching the clinic,” the entry for KT-474 is listed with the “Strategy” of “PROTAC (structure undisclosed)”. However, this is factually incorrect based on publicly available information from the developer, Kymera Therapeutics, and numerous other scientific sources.
– KT-474 is widely reported and recognized as a molecular glue degrader, not a PROTAC.
– It functions by reshaping the surface of the E3 ligase CRBN to recruit and degrade the target protein, IRAK4. This is the hallmark mechanism of a molecular glue.
– In contrast, a PROTAC is a bivalent molecule with two distinct ligands (for the target protein and an E3 ligase) connected by a linker.
A simple search on Kymera Therapeutics’ website or in clinical trial databases (ClinicalTrials.gov identifier NCT04772885) confirms that KT-474 (also known as SAR444656) is described as an IRAK4 degrader using an IMiD-based molecular glue approach. Is there any possible justification or explanation for this misclassification?