CK1 alpha degrader GLB-001

{
  "id": "MLC-T-ONC-012625",
  "term": "CK1 alpha degrader GLB-001",
  "field": "Oncology and biomedicine",
  "definition": "An orally bioavailable molecular glue degrader of casein kinase 1 alpha (CK1alpha; CK1a), with potential antineoplastic activity. Upon oral administration, CK1a degrader GLB-001 targets and binds to CK1a, and to E3 ubiquitin ligase, thereby creating a ternary complex. This induces E3 ligase ubiquitination and proteasome-mediated degradation of CK1a, and inhibits the activity of CK1a. This prevents the enhanced binding of murine double minute X (MDMX) to p53, reduces the formation of CK1a and MDM2 complex, and prevents the interaction of MDM2 with p53. This prevents the inhibition of p53 and increases p53 activity. This induces p53-mediated cell cycle arrest, thereby inhibiting tumor cell proliferation. CK1a, a serine/threonine kinase and a leukemic stem cell target, acts as a tumor suppressor in several cancers through the negative regulation of Wnt/beta-catenin signaling and p53. It negatively regulates p53 by phosphorylating MDMX, thus enhancing binding of MDMX to p53, as well as by forming a complex with MDM2.",
  "synonyms": [
    "MGD GLB-001",
    "CK1a degrader GLB-001",
    "CK1a molecular glue degrader GLB-001"
  ],
  "references": [
    "National Cancer Institute Thesaurus"
  ],
  "url": "https://mlchart.com/terminology/oncology/ck1-alpha-degrader-glb-001/"
}