Preferred Label : Wee1 Kinase Inhibitor Debio 0123;
NCIt synonyms : Wee1 Inhibitor Debio 0123;
NCIt definition : An orally bioavailable inhibitor of the human tyrosine kinase Wee1 (Wee1-like protein
kinase; Wee1A kinase; WEE1hu), with potential antineoplastic sensitizing activity.
Upon oral administration of Debio 0123, this agent targets, binds to and inhibits
Wee1. Inhibition of Wee1 inhibits Cdk1 (Cdc2) phosphorylation, promotes both premature
mitosis and a prolonged mitotic arrest, which results in the accumulation of unrepaired
DNA damage. This leads to apoptosis in susceptible tumor cells, such as p53-deficient
or mutated human cancers that lack the G1 checkpoint, especially in combination with
DNA-damaging chemotherapeutic agents. Unlike normal cells, most p53-deficient or mutated
human cancers lack the G1 checkpoint as p53 is the key regulator of the G1 checkpoint
and these cells rely on the G2 checkpoint for DNA repair to damaged cells. Annulment
of the G2 checkpoint may therefore make p53-deficient tumor cells more vulnerable
to antineoplastic agents and enhance their cytotoxic effect. Overexpression of Wee1
occurs in several cancer types and high expression of Wee1 is associated with poor
outcomes. Wee1 phosphorylates Cdc2 in the Cdc2/cyclin B (CDK1/cyclin B) complex which
blocks progression from G2 into mitosis. The Wee1 tyrosine kinase is activated upon
DNA damage and regulates the G2-M and S cell cycle checkpoints.;
Molecule name : Debio-0123; Debio 0123;
NCI Metathesaurus CUI : CL1407441;
Origin ID : C173426;
UMLS CUI : C5417977;
Semantic type(s)
- concept_is_in_subset
- has_target
