Preferred Label : BTK Degrader HSK29116;
NCIt synonyms : BTK-Protac HSK29116; BTK Protein Degradation Agent HSK29116;
NCIt definition : An orally bioavailable chimeric targeting molecule (CTM) and targeted degrader of
Bruton's tyrosine kinase (BTK; Bruton agammaglobulinemia tyrosine kinase) by using
the proteolysis targeting chimera (PROTAC) technology, with potential antineoplastic
activity. HSK29116 is comprised of an E3 ubiquitin ligase binding moiety conjugated,
via a linker, to a BTK-binding moiety. Upon oral administration, BTK degrader HSK29116
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, HSK29116 may overcome tumor resistance associated with BTK inhibitor-induced
resistance mutations, including the BTK C481 mutation, a resistance mutation in the
BTK active site in which cysteine is substituted for serine at residue 481.;
Molecule name : HSK 29116; HSK-29116;
NCI Metathesaurus CUI : CL1663335;
Origin ID : C180676;
UMLS CUI : C5556550;
Semantic type(s)
- chemical_or_drug_has_physiologic_effect
- concept_is_in_subset
- has_target
