NRX-0492 is an orally active and potent degrader of BTK. NRX-0492 catalyzes ubiquitylation and proteasomal degradation of BTK with DC50≤0.2 nM and DC90≤0.5 nM, respectively. NRX-0492 inhibits B-cell receptor (BCR)-mediated signaling, transcriptional programs, and chemokine secretion. Moreover, NRX-0492 also links a noncovalent BTK-binding domain to Cereblon. Cereblon is an adaptor protein of the E3 ubiquitin ligase complex.
References:
[1]. Zhang D, et al. NRX-0492 degrades wild-type and C481 mutant BTK and demonstrates in vivo activity in CLL patient-derived xenografts. Blood. 2023 Mar 30;141(13):1584-1596.