OncoSignal
Live from Open Targets Platform, fetched 2026-11-11 15:58 UTC. Every row links to its source record.

WEE1 WEE1 G2 checkpoint kinase

ENSG00000166483 · protein coding · Open Targets profile

Acts as a negative regulator of entry into mitosis (G2 to M transition) by protecting the nucleus from cytoplasmically activated cyclin B1-complexed CDK1 before the onset of mitosis by mediating phosphorylation of CDK1 on 'Tyr-15' (PubMed:15070733, PubMed:7743995, PubMed:8348613, PubMed:8428596). Specifically phosphorylates and inactivates cyclin B1-complexed CDK1 reaching a maximum during G2 phase and a minimum as cells enter M phase (PubMed:7743995, PubMed:8348613, PubMed:8428596). Phosphorylation of cyclin B1-CDK1 occurs exclusively on 'Tyr-15' and phosphorylation of monomeric CDK1 does not occur (PubMed:7743995, PubMed:8348613, PubMed:8428596). Its activity increases during S and G2 phases and decreases at M phase when it is hyperphosphorylated (PubMed:7743995). A correlated decrease in protein level occurs at M/G1 phase, probably due to its degradation (PubMed:7743995). {ECO:0000269|PubMed:15070733, ECO:0000269|PubMed:7743995, ECO:0000269|PubMed:8348613, ECO:0000269|PubMed:8428596}.

None of the 2 drugs recorded against WEE1 is approved yet; 1 reached Phase 3

Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.

1 small molecule drug at Phase 3: AZENOSERTIB1 small molecule drug at Phase 2: ADAVOSERTIBSmall molecule 2Phase 3 1Phase 2 1

Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.

In 5 of 15 cancers, the evidence for WEE1 comes mainly from inherited variants

Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.

Inherited (germline) variantsMutations in tumours (somatic)
00.250.50.751actinic keratosisactinic keratosisactinic keratosis: germline 0.72squamous cell carcinomasquamous cell carcinomasquamous cell carcinoma: germline 0.68cutaneous squamous cell carcinomacutaneous squamous cell carcinomacutaneous squamous cell carcinoma: germline 0.68skin cancerskin cancerskin cancer: germline 0.57ovarian cancerovarian cancerfallopian tube cancerfallopian tube cancerprimary peritoneal carcinomaprimary peritoneal carcinomaskin neoplasmskin neoplasmskin neoplasm: germline 0.47small cell lung carcinomasmall cell lung carcinomatriple-negative breast carcinomatriple-negative breast carcinomanon-small cell lung carcinomanon-small cell lung carcinomaacute myeloid leukemiaacute myeloid leukemiaovarian carcinomaovarian carcinomaglioblastomaglioblastomaendometrial serous adenocarcinomaendometrial serous adenocarcinoma

Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.

Tractability

Small molecule
Advanced Clinical, Structure with Ligand, High-Quality Ligand, High-Quality Pocket, Druggable Family
PROTAC
Literature, UniProt Ubiquitination, Database Ubiquitination, Small Molecule Binder

gnomAD loss of function constraint: o/e 0.23260000348091125 (upper bound 0.3532699942588806). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.

Who runs trials of these drugs

Principal investigators and study chairs on 33 registry trials, updated in the last three years, of the most advanced drugs against WEE1 (azenosertib, adavosertib), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.

17 of 33 trials of drugs against WEE1 have sites only in United States

Registry trials of azenosertib, adavosertib updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 19 of 33 have all sites in one country.

Sites only in this groupSites here and elsewhere
United StatesUnited States: 17 trials with sites only hereUnited States: 12 trials with sites here and elsewhere29EuropeEurope: 2 trials with sites only hereEurope: 8 trials with sites here and elsewhere10OtherOther: 1 trials with sites only hereOther: 11 trials with sites here and elsewhere12

Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. Source: ClinicalTrials.gov, fetched live.

16 trials of drugs against WEE1 were stopped early

Terminated, withdrawn and suspended interventional trials of azenosertib, adavosertib, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 16 most recent of 16.

  • terminated · 2026-10-27 · Brandon Huffman, MD · matched by the registry's drug synonyms
    “Study stopped early due to reaching the minimum number of DLTs required for halting the study due to toxicity.”
  • terminated · 2026-06-04 · Filipa Lynce, MD · Azenosertib
    “Zentalis terminated contract due to concern for toxicity safety from previously reported serious adverse events. This study had been designed as a Phase I / Phase II study, but never reached Phase II.”
  • terminated · 2026-01-30 · National Cancer Institute (NCI) · Adavosertib
    “Other - Adverse Events”
  • terminated · 2024-02-20 · National Cancer Institute (NCI) · Adavosertib
    “Inadequate accrual rate”
  • terminated · 2023-09-21 · Merck Sharp & Dohme LLC · adavosertib 20 mg, adavosertib 65 mg
    “The study has been terminated due to business reasons.”
  • terminated · 2023-09-18 · Merck Sharp & Dohme LLC · adavosertib, Placebo to adavosertib
    “The sponsor permanently suspended new enrollment into the trial and discontinued the study; which was not related to any concerns over product safety.”
  • terminated · 2022-12-28 · Joseph Paul Eder · matched by the registry's drug synonyms
    “The study was paused during COVID and without the ability to initiate the 4th arm in the study, the decision was to terminate the study in 2022.”
  • terminated · 2022-09-16 · AstraZeneca · Adavosertib
    “The study terminated because the clinical development programme for Adavosertib has been discontinued”
  • terminated · 2022-09-06 · AstraZeneca · [14C]Adavosertib
    “Study terminated because the clinical development programme for Adavosertib has been discontinued”
  • terminated · 2022-09-02 · AstraZeneca · Adavosertib
    “Study terminated because the clinical development programme for Adavosertib has been discontinued”
  • withdrawn · 2022-06-14 · James Cleary, MD, PhD · Adavosertib
    “manufacturer choice”
  • terminated · 2018-09-20 · Samsung Medical Center · matched by the registry's drug synonyms
    “change regimen”
  • terminated · 2017-05-03 · National Cancer Institute (NCI) · matched by the registry's drug synonyms
    “Inadequate accrual rate”
  • withdrawn · 2017-05-03 · National Cancer Institute (NCI) · matched by the registry's drug synonyms
    “Other - Protocol moved to Disapproved”
  • terminated · 2017-03-29 · AstraZeneca · matched by the registry's drug synonyms
    “The sponsor decided to terminate the study.”
  • terminated · 2016-06-14 · AstraZeneca · matched by the registry's drug synonyms
    “The study was terminated early by the sponsor.”
Paediatric incentives and obligations for WEE1's drugs

For azenosertib, adavosertib: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.

Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs

All 2 drugs and clinical candidates as a table

Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.

DrugTypeHighest stageIndicationsSource records
AZENOSERTIBSmall moleculephase 3fallopian tube cancer, primary peritoneal carcinoma, ovarian cancer, endometrial serous adenocarcinoma, pancreatic adenocarcinoma, cancer, ovarian carcinoma, acute myeloid leukemia, +8 moreOpen Targets · ChEMBL
ADAVOSERTIBSmall moleculephase 2ovarian cancer, cancer, non-small cell lung carcinoma, non-small cell squamous lung carcinoma, fallopian tube cancer, primary peritoneal carcinoma, head and neck cancer, head and neck squamous cell carcinoma, +38 moreOpen Targets · ChEMBL