Preferred Label : Zelebrudomide;
NCIt synonyms : Chimeric Targeting Molecule NX-2127; Bruton's Tyrosine Kinase Degrader NX-2127; CTM NX-2127; BTK Degrader NX-2127;
NCIt definition : An orally bioavailable chimeric targeting molecule (CTM) and targeted degrader of
Bruton's tyrosine kinase (BTK), with potential immunomodulatory drug (IMiD) and antineoplastic
activities. Zelebrudomide is comprised of a cereblon (CRBN)-binding moiety conjugated,
via a linker, to a BTK-binding moiety. Upon administration, zelebrudomide targets
and binds to BTK with its BTK-targeting moiety. Upon binding, the CRBN-binding moiety
recruits CRBN, a component of the CRL4-CRBN E3 ubiquitin ligase complex. This catalyzes
ubiquitination and proteasome-mediated degradation of BTK, and prevents the activation
of the B-cell antigen receptor (BCR) signaling pathway. This prevents both B-cell
activation and BTK-mediated activation of downstream survival pathways. This leads
to an inhibition of the growth of malignant B-cells that overexpress BTK. In addition,
zelebrudomide catalyzes the degradation of CRBN neosubstrates Aiolos (IKZF3) and Ikaros
(IKZF1), two transcription factors regulating T-cell function. This modulates the
activity of the immune system and increases the activation of T-lymphocytes, thereby
increasing T-cell-mediated anti-tumor effects. BTK, a member of the src-related BTK/Tec
family of cytoplasmic tyrosine kinases, is overexpressed in B-cell malignancies; it
plays an important role in B-lymphocyte development, activation, signaling, proliferation
and survival. CRBN, the substrate recognition component of the CRL4-CRBN E3 ubiquitin
ligase complex, plays a key role in the ubiquitination of certain proteins. Compared
to BTK inhibitors, zelebrudomide may overcome tumor resistance associated with BTK
inhibitor-induced resistance mutations.;
UNII : C9V5FHZ2L3;
CAS number : 3024312-52-2;
Molecule name : NX-2127; NX 2127;
NCI Metathesaurus CUI : CL1663074;
Origin ID : C180499;
UMLS CUI : C5556420;
Semantic type(s)
- chemical_or_drug_has_physiologic_effect
- concept_is_in_subset
- has_target
