BTK degrader HSK29116

{
  "id": "MLC-T-ONC-012139",
  "term": "BTK degrader HSK29116",
  "field": "Oncology and biomedicine",
  "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.",
  "synonyms": [
    "BTK-Protac HSK29116",
    "BTK protein degradation agent HSK29116"
  ],
  "references": [
    "National Cancer Institute Thesaurus"
  ],
  "url": "https://mlchart.com/terminology/oncology/btk-degrader-hsk29116/"
}