Loading
A checkpoint kinase that gives cells time to fix DNA before dividing. Removing it forces damaged cancer cells into a fatal division.
WEE1 is a checkpoint kinase that inhibits CDK1 to enforce the G2/M checkpoint, giving cells time to repair DNA before dividing. TP53-mutant cells have lost their G1 checkpoint and depend on WEE1 to avoid entering mitosis with damaged DNA, so inhibiting it forces them into a lethal division. Adavosertib showed activity in uterine serous carcinoma and other TP53-mutant tumours, but its development was paused; azenosertib (ZN-c3) and Debio 0123 continue in ovarian and other cancers. The strongest rationale is in CCNE1-amplified disease, seen in 15 to 20 percent of ovarian cancers, where TP53 mutation is also near-universal. Haematological and gastrointestinal toxicity have limited dosing, and no WEE1 inhibitor is yet approved. In plain terms, removing this checkpoint pushes damaged cancer cells into a division they cannot survive.
In plain words · A checkpoint kinase that gives cells time to fix DNA before dividing. Removing it forces damaged cancer cells into a fatal division.
A checkpoint kinase that gives cells time to fix DNA before dividing. Removing it forces damaged cancer cells into a fatal division.
Inhibits CDK1 to enforce the G2/M checkpoint; TP53-mutant cells depend on it.
1 product aims at WEE1: small molecules. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
Broadly expressed or essential: HPA lists WEE1 among essential proteins and finds the RNA at low tissue specificity; the 1 medicine aimed at it (Azenosertib) act on the wild-type protein, so normal tissue is exposed and the therapeutic window comes from the tumour's faster division or its dependence on the protein. HPA WEE1: RNA low tissue specificity; high antibody staining in 4 normal tissues; highest cancer staining testis cancer (5 of 12 high). Distribution: 3 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Ovarian cancer, Endometrial cancer, Breast cancer (all types)); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 7 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas WEE1 tissue; Open Targets ENSG00000166483 associations
First described 1991. Earliest sequence paper UniProt cites for the protein: Igarashi et al, Nature, 1991, "Wee1(+)-like gene in human cells". Source.
Inhibits CDK1 to enforce the G2/M checkpoint; TP53-mutant cells depend on it.
RNA: low tissue specificity, detected in all normal tissues.
Medium: Bone marrow, Breast, Bronchus, Endometrium, Epididymis, Fallopian tube, Lymph node, Parathyroid gland.
Medium only: breast cancer, cervical cancer, colorectal cancer, glioma.
HPA WEE1 tissue · HPA WEE1 pathology · HPA protein class: Essential proteins
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Ovarian cancer | 15-20% | CCNE1 amplification (dependency context) | TP53 mutation ~95% | cBioPortal (TCGA) |
| Endometrial cancer | n/a | Uterine serous carcinoma context | Wikipedia |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Azenosertib is an experimental small-molecule drug from K-, Beta in phase 3 trials for ovarian cancer, aimed at WEE1.
Query for this target: (TITLE:"WEE1" OR ABSTRACT:"WEE1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about WEE1, not a curated reading list.
Shares DNA replication stress, Uterine carcinosarcoma, The p53 network (guardian of the genome), p53-abnormal endometrial cancer, including uterine serous carcinoma and the tag ddr.
Shares Azenosertib, Zentalis Pharmaceuticals, Ovarian cancer.
Shares Synthetic lethality: paired dependencies, DNA damage response & homologous recombination, Double-strand break repair: HR versus end joining, Endometrial cancer.
Shares DNA replication stress, DNA damage response & homologous recombination, Checkpoint (two meanings).
Shares Synthetic lethality: paired dependencies, DNA damage response & homologous recombination, Double-strand break repair: HR versus end joining.
Shares Cell cycle, The cell-cycle engine (cyclins & CDKs), p53 / RB / cell-cycle checkpoint.
Shares Azenosertib, Ovarian cancer.
Shares Cell cycle, The cell-cycle engine (cyclins & CDKs), p53 / RB / cell-cycle checkpoint.