zelebrudomide

Zelebrudomide is an orally bioavailable small molecule chimeric targeting molecule (CTM) designed as a targeted degrader of Bruton's tyrosine kinase (BTK) and also acts as a "molecular glue" targeting transcription factors IKZF1 (Ikaros) and IKZF3 (Aiolos). It is a proteolysis-targeting chimera (PROTAC) comprising a cereblon (CRBN)-binding moiety tethered to a BTK-binding moiety. Upon administration, zelebrudomide binds BTK and recruits CRBN, a component of the CRL4-CRBN E3 ubiquitin ligase complex, resulting in ubiquitination and proteasome-mediated degradation of both BTK and the neosubstrate transcription factors IKZF1 and IKZF3. This leads to inhibition of B-cell receptor signaling, suppression of malignant B-cell growth, and immunomodulation via increased T-cell activation. Zelebrudomide is being developed primarily for B-cell malignancies, including various lymphomas and chronic lymphocytic leukemia, and is currently in phase 1 clinical trials. It is being developed by Nurix Therapeutics[1][2][3][5][6][7][9].

Other names

zelebrudomideNX-2127NX2127NX 2127compound 28compound28compound-28