Protein / target

Wee1-like protein kinase

Encoded byWEE1P30291Homo sapiensSwiss-Prot

UniProt: P30291 Ensembl: ENSG00000166483 HGNC: HGNC:12761 NCBI Gene: 7465

Clinical-stage

Therapeutic maturity

Clinical candidates

Clinical trials

Small-molecule tractable

Druggability

Advanced Clinical

Protein at a glance

Biological role

Non-membrane spanning protein tyrosine kinase

Strongest disease association

Actinic keratosis

Via encoding gene WEE1 · Genetic evidence · score 0.67

Therapeutic position

Clinically advancing target

Small molecules

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

View complete UniProt function annotation

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)

Subcellular location

Nucleus

Domains and Gene Ontology detail (14)

Domains & features

Protein kinase

Gene Ontology

Ccytoplasm
Cnucleolus
Cnucleoplasm
Cnucleus
FATP binding
Fmagnesium ion binding
Fnon-membrane spanning protein tyrosine kinase activity
Fprotein tyrosine kinase activity
Pcell division
PG2/M transition of mitotic cell cycle
Pnegative regulation of G1/S transition of mitotic cell cycle
Pnegative regulation of G2/M transition of mitotic cell cycle

646 aa · 72 kDa · 2 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Cell-cycle regulationGOKinase signallingGO

View supporting evidence

Cell-cycle regulation

·G2/M transition of mitotic cell cycle
·negative regulation of G1/S transition of mitotic cell cycle
·negative regulation of G2/M transition of mitotic cell cycle

Kinase signalling

·non-membrane spanning protein tyrosine kinase activity
·protein tyrosine kinase activity

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Drugs targeting this protein

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

Adavosertib

Narrow target profilePhase 2Inhibitor

Serine/threonine-protein kinase WEE1 inhibitor

Direct interaction with this protein · Only this protein recorded as a target

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene WEE1

Gene-level evidence surfaced through the gene WEE1that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Actinic keratosis

0.68Moderately supported

Genetic evidence dominant · Open Targets 0.41

Carcinoma, Squamous Cell

0.61Moderately supported

Genetic evidence dominant · Open Targets 0.37

Skin squamous cell carcinoma

0.60Moderately supported

Genetic evidence dominant · Open Targets 0.37

Skin Neoplasms

0.50Moderately supported

Genetic evidence dominant · Open Targets 0.30

Ovarian Neoplasms

0.44Limited support

Clinical evidence dominant · Open Targets 0.32

View evidence synthesis (5)

Actinic keratosisModerately supported

0.68

agreement 0.54–0.81

Genetic100%Literature0%

Open Targets aggregate 0.41 · 2 independent evidence families

Carcinoma, Squamous CellModerately supported

0.61

agreement 0.47–0.75

Genetic96%Literature4%

Open Targets aggregate 0.37 · 2 independent evidence families

Skin squamous cell carcinomaModerately supported

0.60

agreement 0.47–0.74

Genetic100%Literature1%

Open Targets aggregate 0.37 · 2 independent evidence families

Skin NeoplasmsModerately supported

0.50

agreement 0.36–0.64

Genetic98%Literature2%

Open Targets aggregate 0.30 · 2 independent evidence families

Ovarian NeoplasmsLimited support

0.44

agreement 0.28–0.59

Clinical77%Literature23%

Open Targets aggregate 0.32 · 2 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations

Neurodegenerative Diseases0.52

Actinic keratosis0.41

Autoimmune disorder of central nervous system0.37

Carcinoma, Squamous Cell0.37

Skin squamous cell carcinoma0.37

Ovarian Neoplasms0.32

Skin Neoplasms0.30

Drug development

2 compounds recorded · 2 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 1 drug that targets this protein in Forefront's canonical graph: these count different sets and are not a subset relation.

View all recorded compounds (2)

ADAVOSERTIBPhase 2

AZENOSERTIBPhase 3

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Strong

Advanced Clinical and Structure with Ligand support this modality.

Protein degraders — Emerging

Feasibility evidence (literature and uniprot ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (9)

SM · Advanced ClinicalSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyPR · LiteraturePR · UniProt UbiquitinationPR · Database UbiquitinationPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

A Phase 2 Study of AZD1775 in SETD2-Deficient Advanced Solid Tumor MalignanciesPHASE2

ACTIVE_NOT_RECRUITING · via Adavosertib · NCT03284385

EFFORT: Efficacy of AZD1775 in Parp Resistance; A Randomized 2-Arm, Non-Comparative Phase 2 Study of AZD1775 Alone or AZD1775 and Olaparib in Women With Ovarian Cancer Who Have Progressed During PARP InhibitionPHASE2

ACTIVE_NOT_RECRUITING · via Adavosertib · NCT03579316

Prostate Cancer Biomarker Enrichment and Treatment Selection (PC-BETS) StudyPHASE2

ACTIVE_NOT_RECRUITING · via Adavosertib · NCT03385655

MATCH Treatment Subprotocol Z1I: Phase II Study of AZD1775 in Patients With Tumors Containing BRCA1 and BRCA2 MutationsPHASE2

ACTIVE_NOT_RECRUITING · via Adavosertib · NCT04439227

View all trials (24)

European Proof-of-Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory TumorsPHASE1/PHASE2

RECRUITING · via Adavosertib · NCT02813135

Molecular Analysis for Therapy Choice (MATCH)PHASE2