Preferred Label : BTK Degrader BGB-16673;
NCIt synonyms : BTK-Protac BGB-16673; BTK Protein Degradation Agent BGB-16673;
NCIt definition : An orally bioavailable, targeted degrader of Bruton's tyrosine kinase (BTK; Bruton
agammaglobulinemia tyrosine kinase) by using the proteolysis targeting chimera (PROTAC)
technology, with potential antineoplastic activity. BGB-16673 is comprised of an E3
ubiquitin ligase binding moiety conjugated, via a linker, to a BTK-binding moiety.
Upon oral administration, BTK degrader BGB-16673 targets and binds to BTK with its
BTK-targeting moiety, thereby inhibiting its activity. Upon binding, the E3 ligase-binding
moiety binds to cereblon (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. 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. Compared to BTK inhibitors,
BGB-16673 may overcome tumor resistance associated with BTK inhibitor-induced resistance
mutations, including the BTK C481S mutation, a resistance mutation in the BTK active
site in which cysteine is substituted for serine at residue 481.;
Molecule name : BGB 16673; BGB-16673;
NCI Metathesaurus CUI : CL1770940;
Origin ID : C182615;
UMLS CUI : C5666890;
Semantic type(s)
- chemical_or_drug_has_physiologic_effect
- concept_is_in_subset
- has_target
