Preferred Label : CK1 Alpha Degrader GLB-001;
NCIt synonyms : MGD GLB-001; CK1a Molecular Glue Degrader GLB-001; CK1a Degrader GLB-001;
NCIt 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.;
Molecule name : GLB-C183-A-2; GLB 001; GLB-001;
NCI Metathesaurus CUI : CL1922071;
Origin ID : C202928;
UMLS CUI : C5907983;
Semantic type(s)
- concept_is_in_subset
- has_target
