Catalog No.: PC-24021Not For Human Use, Lab Use Only.
NRX-0492 is a potent, selective cereblon (CRBN)-basesd PROTAC degrader of wild-type and C481 mutant BTK with DC50 of 0.1 nM and 0.2 nM, and DC90 of 0.3 nM and 0.5 nM in TMD8 cells expressing WT or C481S mutant BTK respectively.
NRX-0492 is a potent, selective cereblon (CRBN)-basesd PROTAC degrader of wild-type and C481 mutant BTK with DC50 of 0.1 nM and 0.2 nM, and DC90 of 0.3 nM and 0.5 nM in TMD8 cells expressing WT or C481S mutant BTK respectively. NRX-0492 has IC50 of 1.2 nM and 9 nM for BTK WT protein and CRBN respectively. NRX-0492 shows binding affinities to BTK proteins harboring 2 acquired inhibitor-resistance mutations (C481S or T474I) with IC50 of 2.7 nM and 1.2 nM in FRET competition assays. NRX-0492 selectively degrades BTK via a cereblon (CRBN)- and proteasome-dependent mechanism. NRX-0492 decreases in IKZF1 and IKZF3 levels in TMD8 and MOLT4 cells. NRX-0492 induces sustained E3 ligase-dependent BTK degradation in primary CLL cells. NRX-0492 inhibits BCR and NF-κB signaling, exhibits strong downregulation of BCR, NF-κB, and MYC regulated genes consistent with effective inhibition of BTK-dependent signaling in CLL cells from patients. NRX-0492 inhibits treatment-naïve CLL cell proliferation and activation in in the CLL PDX model of treatment- naïve CLL, degrades C481S mutant BTK in CLL cells from patients progressing on IBR.
