{"meta":{"totalResults":1,"from":0},"results":[{"aliases":[{"type":"CodeName","name":"BGB-16673"},{"type":"Synonym","name":"BTK protein degradation agent BGB-16673"},{"type":"Synonym","name":"BTK-protac BGB-16673"},{"type":"CodeName","name":"BGB 16673"},{"type":"CodeName","name":"BGB16673"}],"definition":{"html":"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.","text":"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."},"drugInfoSummaryLink":null,"nciConceptId":"C182615","nciConceptName":"BTK Degrader BGB-16673","termId":806209,"name":"BTK degrader BGB-16673","firstLetter":"b","type":"DrugTerm","termNameType":"PreferredName","prettyUrlName":"btk-degrader-bgb-16673"}],"links":null}