{"entity":{"id":"wee1","kind":"target","name":"WEE1","aka":[],"tldr":"A checkpoint kinase that gives cells time to fix DNA before dividing. Removing it forces damaged cancer cells into a fatal division.","summary":"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.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Wee1-like_protein_kinase","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Wee1-like_protein_kinase"}],"tags":["ddr"],"related":[],"cancers":["ovarian","endometrial","tnbc"],"sections":[],"technologies":[],"targets":[],"drugs":["azenosertib"],"companies":["acrivon-therapeutics","zentalis-pharmaceuticals"],"institutions":[],"pathways":["ddr","p53-cell-cycle"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"WEE1","role":[],"sources":[],"specificity":"broadly-expressed","distribution":"few-types","specificityNote":"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.)","specificitySources":[{"label":"Human Protein Atlas WEE1 tissue","url":"https://www.proteinatlas.org/ENSG00000166483-WEE1/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000166483 associations","url":"https://platform.opentargets.org/target/ENSG00000166483/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:12761","ensembl":"ENSG00000166483","uniprot":"P30291","entrez":"7465","firstDescribed":1991,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Igarashi et al, Nature, 1991, \"Wee1(+)-like gene in human cells\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/1840647/","biology":"Inhibits CDK1 to enforce the G2/M checkpoint; TP53-mutant cells depend on it.","whereFound":["TP53-mutant, CCNE1-amplified tumours"],"targetClass":"kinase","prevalence":[{"cancerId":"ovarian","pct":"15-20","measure":"CCNE1 amplification (dependency context)","source":"https://www.cbioportal.org/study/summary?id=ov_tcga_pan_can_atlas_2018","note":"TP53 mutation ~95%"},{"cancerId":"endometrial","pct":"n/a","measure":"Uterine serous carcinoma context","source":"https://en.wikipedia.org/wiki/Wee1-like_protein_kinase"}]},"route":"/targets/wee1/","neighbours":{"cancer":[{"id":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"endometrial-p53-abnormal","kind":"cancer","name":"p53-abnormal endometrial cancer, including uterine serous carcinoma","route":"/cancers/endometrial-p53-abnormal/"},{"id":"platinum-sensitive-ovarian-cancer","kind":"cancer","name":"Platinum-sensitive ovarian cancer","route":"/cancers/platinum-sensitive-ovarian-cancer/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"},{"id":"uterine-carcinosarcoma","kind":"cancer","name":"Uterine carcinosarcoma","route":"/cancers/uterine-carcinosarcoma/"}],"drug":[{"id":"azenosertib","kind":"drug","name":"Azenosertib","route":"/drugs/azenosertib/"}],"company":[{"id":"acrivon-therapeutics","kind":"company","name":"Acrivon Therapeutics","route":"/companies/acrivon-therapeutics/"},{"id":"debiopharm","kind":"company","name":"Debiopharm","route":"/companies/debiopharm/"},{"id":"zentalis-pharmaceuticals","kind":"company","name":"Zentalis Pharmaceuticals","route":"/companies/zentalis-pharmaceuticals/"}],"pathway":[{"id":"circadian-control","kind":"pathway","name":"Circadian control","route":"/pathways/circadian-control/"},{"id":"ddr","kind":"pathway","name":"DNA damage response & homologous recombination","route":"/pathways/ddr/"},{"id":"replication-stress","kind":"pathway","name":"DNA replication stress","route":"/pathways/replication-stress/"},{"id":"homologous-recombination-repair","kind":"pathway","name":"Double-strand break repair: HR versus end joining","route":"/pathways/homologous-recombination-repair/"},{"id":"p53-cell-cycle","kind":"pathway","name":"p53 / RB / cell-cycle checkpoint","route":"/pathways/p53-cell-cycle/"},{"id":"synthetic-lethality-map","kind":"pathway","name":"Synthetic lethality: paired dependencies","route":"/pathways/synthetic-lethality-map/"},{"id":"cell-cycle-engine-cdks","kind":"pathway","name":"The cell-cycle engine (cyclins & CDKs)","route":"/pathways/cell-cycle-engine-cdks/"},{"id":"p53-mdm2-axis","kind":"pathway","name":"The p53 network (guardian of the genome)","route":"/pathways/p53-mdm2-axis/"}],"technology":[{"id":"synthetic-lethality-approaches","kind":"technology","name":"Synthetic lethality approaches","route":"/technologies/synthetic-lethality-approaches/"}],"term":[{"id":"cell-cycle","kind":"term","name":"Cell cycle","route":"/terms/cell-cycle/"},{"id":"checkpoint","kind":"term","name":"Checkpoint (two meanings)","route":"/terms/checkpoint/"}]}}