Single Biggest Cancer Dictionary in the World
What is BTK degrader HSK29116?
BTK degrader HSK29116
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.