Compound class:
Synthetic organic
Comment: NX-2127 is an orally bioavailable protein degrader molecule. It reduces levels of both Bruton's tyrosine kinase (BTK) and the IKZF transcription factors Ikaros (IKZF1) and Aiolos (IKZF3) through targeted ubiquitination and proteasomal degradation. NX-2127 acts as a dual PROTAC (through recruitment of cereblon) and molecular glue (degradation of the neosubstrate transcription factors). It is predicted that this approach can achieve clinical efficacy, even in the presence of BTK mutations that confer resistance to clinically used kinase inhibitor drugs.
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Bioactivity Comments |
A poster (presented at the American Society of Hematology annual meeting in 2020) provided DC50 values of 4 nM in wild type TMD8 cells, and 13 nM in TMD8 cells with the BTKC481S covalent BTK inhibitor resistance mutation. |