^
over1year
-----NRX-0492 Degrades Wildtype and C481 Mutant BTK and Demonstrates in vivo Activity in CLL Patient Derived Xenografts. (PubMed, Blood)
In in vitro testing against treatment-naïve CLL samples, NRX-0492 was as effective as ibrutinib at inhibiting BCR mediated signaling, transcriptional programs, and chemokine secretion. Oral bioavailability, >90% degradation of BTK at sub-nanomolar concentrations and sustained pharmacodynamic effects after drug clearance make this class of targeted protein degraders uniquely suitable for clinical translation, in particular as a strategy to overcome BTK inhibitor resistance. Clinical studies testing this approach have been initiated (NCT04830137, NCT05131022).
Preclinical • Journal
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CRBN (Cereblon)
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BTK C481S • BTK C481
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Imbruvica (ibrutinib) • NRX0492