Preferred Label : BTK Degrader NX-5948;
NCIt synonyms : Chimeric Targeting Molecule NX-5948; Bruton's Tyrosine Kinase Degrader NX-5948;
NCIt definition : An orally bioavailable chimeric targeting molecule (CTM) and targeted degrader of
Bruton's tyrosine kinase (BTK), with potential antineoplastic activity. NX-5948 is
comprised of a cereblon (CRBN)-binding moiety conjugated, via a linker, to a BTK-binding
moiety. Upon oral administration, BTK degrader NX-5948 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. NX-5948 does not catalyze the degradation of CRBN neosubstrates
and transcription factors Aiolos (IKZF3) and Ikaros (IKZF1), and does not possess
immunomodulatory activity. 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. NX-5948 may overcome tumor
resistance associated with BTK inhibitor-induced resistance mutations. In addition,
NX-5948 is able to cross the blood-brain barrier (BBB) and thus potentially useful
in the treatment of central nervous system (CNS) metastases.;
Molecule name : NX-5948; NX 5948;
NCI Metathesaurus CUI : CL1913063;
Origin ID : C192892;
UMLS CUI : C5785492;
Semantic type(s)
- chemical_or_drug_has_physiologic_effect
- concept_is_in_subset
- has_target
