Characterization of the activity of KTX-1001, a small molecule inhibitor of multiple myeloma SET domain using surface plasmon resonance.

ABSTRACT: KTX-1001 is a small molecule inhibitor of NSD2 in clinical development for multiple myeloma. It was identified as a potent and selective inhibitor of NSD2 (also known as MMSET) using a high-throughput biochemical assay with LC/MS-MS detection of SAH production as the endpoint. Subsequent evaluation of the binding of KTX-1001 to its target was conducted using surface plasmon resonance to quantify on-rate, off-rate, and equilibrium dissociation constant utilizing the SET domain as the immobilized target. In this format, no saturable or specific binding could be observed, despite the potent activity in the biochemical assay using full length NSD2 and radiolabeled SAM. To interrogate the discordance between potent activity and the lack of detectable binding, a series of experiments were design

SUBMITTER: Lewis CA 

PROVIDER: S-EPMC12284498 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature