Preferred Label : Zedoresertib;
NCIt synonyms : Wee1 Inhibitor Debio 0123; Wee1 Kinase 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, zedoresertib 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.;
UNII : M6Q5T59DJQ;
CAS number : 2243882-74-6;
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
