WEE1

Summary

WEE1 (WEE1 G2 checkpoint kinase, HGNC:12761) is a protein-coding gene on chromosome 11p15.4, encoding Wee1-like protein kinase (P30291). 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’. In precision oncology, WEE1 RS3910384 confers sensitivity to Platinum Compound + Gemcitabine in Lung Non-small Cell Carcinoma (CIViC Level B). It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

This gene encodes a nuclear protein, which is a tyrosine kinase belonging to the Ser/Thr family of protein kinases. This protein catalyzes the inhibitory tyrosine phosphorylation of CDC2/cyclin B kinase, and appears to coordinate the transition between DNA replication and mitosis by protecting the nucleus from cytoplasmically activated CDC2 kinase.

Source: NCBI Gene 7465 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 71 total
• Druggable target: yes — 27 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_003390

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12761
Approved symbol	WEE1
Name	WEE1 G2 checkpoint kinase
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Aliases	WEE1A
Ensembl gene	ENSG00000166483
Ensembl biotype	protein_coding
OMIM	193525
Entrez	7465

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 8 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay

ENST00000299613, ENST00000450114, ENST00000524549, ENST00000524612, ENST00000527848, ENST00000530175, ENST00000530712, ENST00000532275, ENST00000680141, ENST00000681684, ENST00000919883, ENST00000919884

RefSeq mRNA: 2 — MANE Select: NM_003390 NM_001143976, NM_003390

CCDS: CCDS44536, CCDS7800

Canonical transcript exons

ENST00000450114 — 11 exons

Exon	Start	End
ENSE00001103404	9585258	9585353
ENSE00001221084	9581532	9581678
ENSE00001221092	9577142	9577263
ENSE00001758799	9573670	9574509
ENSE00001805457	9588449	9589985
ENSE00003462644	9575888	9576093
ENSE00003473708	9576230	9576293
ENSE00003515153	9586449	9586619
ENSE00003603677	9586711	9586856
ENSE00003632438	9585442	9585527
ENSE00003686256	9576487	9576659

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 98.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.7926 / max 261.2606, expressed in 1693 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
112985	20.1708	1642
112986	1.8051	882
112991	0.8432	530
112987	0.8291	538
112993	0.7264	395
112988	0.5483	330
112984	0.5482	316
112994	0.4996	230
112990	0.2776	121
112983	0.2391	122

Top tissues by expression

285 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	98.95	gold quality
upper leg skin	UBERON:0004262	97.75	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.02	gold quality
cauda epididymis	UBERON:0004360	96.66	gold quality
mucosa of stomach	UBERON:0001199	96.58	gold quality
buccal mucosa cell	CL:0002336	96.43	gold quality
embryo	UBERON:0000922	96.24	gold quality
cervix squamous epithelium	UBERON:0006922	96.21	gold quality
ganglionic eminence	UBERON:0004023	96.17	gold quality
bronchial epithelial cell	CL:0002328	95.57	gold quality
skin of abdomen	UBERON:0001416	95.56	gold quality
corpus epididymis	UBERON:0004359	95.52	gold quality
oviduct epithelium	UBERON:0004804	95.44	gold quality
gall bladder	UBERON:0002110	95.05	gold quality
epithelium of mammary gland	UBERON:0003244	95.05	gold quality
mammary duct	UBERON:0001765	94.98	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.95	gold quality
mucosa of urinary bladder	UBERON:0001259	94.29	gold quality
cervix epithelium	UBERON:0004801	94.20	gold quality
stromal cell of endometrium	CL:0002255	94.03	gold quality
placenta	UBERON:0001987	93.99	gold quality
epithelium of bronchus	UBERON:0002031	93.99	gold quality
bronchus	UBERON:0002185	93.73	gold quality
right atrium auricular region	UBERON:0006631	93.70	gold quality
zone of skin	UBERON:0000014	93.65	gold quality
skin of leg	UBERON:0001511	93.50	gold quality
endometrium	UBERON:0001295	93.39	gold quality
cardiac atrium	UBERON:0002081	93.32	gold quality
calcaneal tendon	UBERON:0003701	93.28	gold quality
epithelium of nasopharynx	UBERON:0001951	92.97	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-36552	yes	255.27
E-MTAB-10287	yes	32.84
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, AR, E2F4, FOS, JUN, KDM4B, KLF2, KLF3, KLF6, SP1, TBPL1, TP53

miRNA regulators (miRDB)

133 targeting WEE1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-144-3P	99.94	73.98	2698

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• Wee-1 may serve as a key regulator of both HIV type 1 Vpr- and gamma irradiation-mediated apoptosis (PMID:12525641)
• increases of cyclin D1, cyclin-dependent kinase 4, cyclin E, cyclin A, and Wee1 play an important role in the development of hepatocellular carcinoma from cirrhosis (PMID:12601350)
• Proteasome-dependent degradation of this protein is inhibited in G2-arrested Hep3B cells by TGF beta 1. (PMID:12669309)
• WEE1 is directly transactivated by and increased in association with c-Fos/AP-1. (PMID:14534529)
• Loss of Wee1 expression may have a potential role in promoting tumor progression and may be a significant prognostic indicator in NSCLC. (PMID:14760118)
• beta-TrCP-dependent degradation of Wee1A is important for the normal onset of M-phase in vivo. (PMID:15070733)
• the induction of Cdc2 phosphorylation due to the increase of Wee1 and Myt1 as well as the reduction of Cdc2 and cyclin B1 are involved in 1,25[OH]2VD3-induced G2/M arrest of keratinocytes. (PMID:15175024)
• Inhibiting Hsl7 delayed mitosis but overexpression overrode the replication checkpoint, accelerating Wee1 destruction. Checkpoint activation disrupted Hsl7-Wee1 binding which was restored by polo-like kinase. Hsl7 is a replication checkpoint component (PMID:15583029)
• Level of WEE1 is regulated by KLF2 and enhanced KLF2 expression sensitizes cells to DNA damage-induced apoptosis. (PMID:15735666)
• Akt protein phosphorylation and inactivation of WEE1 promote cell cycle progression at G2/M transition. (PMID:15964826)
• our studies indicate that the 2-ME(2)-induced upregulation of wee1 and subsequent cdc2 phosphorylation are mediated through mitogen-activated protein kinase (MAPK)-ERK-JNK signaling pathways. (PMID:16533053)
• Gamma-irradiated human primary prostate epithelial cells were unable to enforce cell cycle checkpoint arrest and had sustained Cdk2-associated kinase activity because of a lack of inhibitory Cdk phosphorylation by Wee1A tyrosine kinase. (PMID:17431037)
• WEE1 can be introduced to rescue cells from the damage caused by certain antineoplastic agents. (PMID:17687495)
• Significant percentage of the total endogenous Crk II partitions in the nucleus in mammalian cells, where it forms distinct complexes with DOCK180, Wee1, and Abl. (PMID:17764157)
• HIV-1 Vpr binds to the N lobe of the Wee1 kinase domain and enhances kinase activity for CDC2. (PMID:18385244)
• These findings support the view that CK2beta regulates various intracellular processes by modulating the activity of protein kinases that are distinct from CK2. (PMID:18560763)
• HSP90 inhibition abrogates the topoisomerase I poison-induced G2/M checkpoint in p53-null tumor cells by depleting CHK1 and WEE1. (PMID:18820127)
• Cdc34 is a functional target of let-7 and that let-7 induces down-regulation of Cdc34, stabilization of the Wee1 kinase, and an increased fraction of cells in G(2)/M in primary fibroblasts. (PMID:19126550)
• Results identify WEE1 as a potential molecular target in breast cancer. (PMID:19821025)
• These studies identify a novel bifunctional regulatory element in Wee1 that mediates cyclin A/Cdk2 association and nuclear export. (PMID:19858290)
• Abrogation of G(2) arrest by inhibition of ATM and ATR, Chk1, and Wee1 suppressed JCV genome replication. (PMID:19903823)
• multiple regions of Wee1 control its destruction (PMID:20038582)
• analysis of interaction sites between Wee1 kinase and the regulatory beta-subunit of protein kinase CK2 (PMID:20372791)
• Regulation of Wee1 kinase by miRs may be linked to pituitary tumorigenesis. (PMID:20668041)
• WEE1 is a major regulator of the G(2) checkpoint in glioblastoma cells. (PMID:20832752)
• The over-expression of the naturally under-expressed miR-128 in glioma cells resulted in the inhibition of WEE1 in glioblastoma cells. (PMID:21358821)
• WEE1 inhibition may be a promising strategy to enhance the radiotherapy effect in patients with OS. (PMID:21529352)
• Results demonstrate a novel role of Wee1 in controlling Mus81-Eme1 and DNA replication in human cells. (PMID:21859861)
• Sensitization effects of WEE1 inhibition on TRAIL-mediated apoptosis in breast cancer cell lines. (PMID:22112940)
• Elevated WEE1 expression is associated with acute myeloid leukemia. (PMID:22289989)
• WEE1 accumulation and deregulation of S-phase proteins mediate MLN4924 potent inhibitory effect on Ewing sarcoma cells. (PMID:22641220)
• Data identify Cdc20, USP44, and Wee1 as relevant Fcp1 targets. (PMID:22692537)
• results reveal the importance of Wee1 as a prognostic biomarker in melanomas, and indicate a potential role for targeted therapy, alone or in combination with other agents (PMID:22719872)
• study shows WEE1 expression in malignant melanoma is directly regulated by miR-195; miR-195-mediated downregulation of WEE1 in metastatic lesions may help to overcome cell cycle arrest under stress conditions in the local tissue microenvironment to allow unrestricted growth of tumour cells (PMID:22847610)
• The results suggested that deregulated CDK1 activity, such as that occurring following inhibition of WEE1 kinase, induces replication stress and loss of genomic integrity through increased firing of replication origins and subsequent nucleotide shortage. (PMID:22907750)
• Wee1 inhibition sensitizes cancer cells to Hsp90 inhibitors. (PMID:22935698)
• Loss-of-function and gain-of-function studies showed that miR-15 family members controlled the expression of WEE1 and CHK1. (PMID:22942255)
• These data support the hypothesis that Cdc14A counteracts Cdk1-cyclin B1 activity through Wee1 dephosphorylation. (PMID:23051732)
• AURKB and WEE1 are targets and biomarkers of therapeutic efficacy, lying downstream of (V600E)B-RAF in melanomas. (PMID:23416158)
• miR-497 is a candidate tumor suppressor in neuroblastoma, through the direct targeting of WEE1. (PMID:23531080)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	wee1	ENSDARG00000093864
mus_musculus	Wee1	ENSMUSG00000031016
rattus_norvegicus	Wee1	ENSRNOG00000010017
drosophila_melanogaster	Wee1	FBGN0011737

Paralogs (8): EIF2AK2 (ENSG00000055332), EIF2AK1 (ENSG00000086232), STK35 (ENSG00000125834), PKMYT1 (ENSG00000127564), EIF2AK4 (ENSG00000128829), EIF2AK3 (ENSG00000172071), PDIK1L (ENSG00000175087), WEE2 (ENSG00000214102)

Protein

Protein identifiers

Wee1-like protein kinase — P30291 (reviewed: P30291)

Alternative names: Wee1A kinase

All UniProt accessions (6): A0A7P0TBN9, E9PQ51, E9PRI3, P30291, E9PRU3, H0YEJ2

UniProt curated annotations — full annotation on UniProt →

Function. 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’. Specifically phosphorylates and inactivates cyclin B1-complexed CDK1 reaching a maximum during G2 phase and a minimum as cells enter M phase. Phosphorylation of cyclin B1-CDK1 occurs exclusively on ‘Tyr-15’ and phosphorylation of monomeric CDK1 does not occur. Its activity increases during S and G2 phases and decreases at M phase when it is hyperphosphorylated. A correlated decrease in protein level occurs at M/G1 phase, probably due to its degradation.

Subcellular location. Nucleus.

Post-translational modifications. Phosphorylated during M and G1 phases. Also autophosphorylated. Phosphorylation at Ser-642 by BRSK1 and BRSK2 in post-mitotic neurons, leads to down-regulate WEE1 activity in polarized neurons. Phosphorylated at Ser-53 and Ser-123 by PLK1 and CDK1, respectively, generating an signal for degradation that can be recognized by the SCF(BTRC) complex, leading to its ubiquitination and degradation at the onset of G2/M phase. Dephosphorylated at Thr-239 by CTDP1. Dephosphorylated at Ser-53 and Ser-123 by the serine/threonine-protein phosphatase 2A preventing its ubiquitin-mediated degradation. Ubiquitinated and degraded at the onset of G2/M phase.

Activity regulation. Synthesis is increased during S and G2 phases, presumably by an increase in transcription; activity is decreased by phosphorylation during M phase. Protein levels fall in M phase as a result of decreased synthesis combined with degradation. Activity seems to be negatively regulated by phosphorylation upon entry into mitosis, although N-terminal phosphorylation might also regulate the protein stability via protection from proteolysis or might regulate the subcellular location.

Cofactor. Binds 2 magnesium ions per subunit.

Similarity. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WEE1 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P30291-1	1	yes
P30291-2	2

RefSeq proteins (2): NP_001137448, NP_003381* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017164	Wee1-like_protein_kinase	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR050339	CC_SR_Kinase	Family

Pfam: PF00069

Enzyme classification (BRENDA):

• EC 2.7.10.2 — non-specific protein-tyrosine kinase (BRENDA: 41 organisms, 396 substrates, 479 inhibitors, 43 Km, 32 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.014–17.64	12
[KDSRC KINASE]-L-TYROSINE	0.0057–0.24	12
POLY(GLU4-TYR)	0.018–0.659	10
EEEEYIQ[DP]-8-HYDROXY-5-(N,N-DIMETHYLSULFONAMIDO	0.057	1
S1 PEPTIDE	0.037	1
EEEEY	—	0

Catalyzed reactions (Rhea), 1 shown:

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)

UniProt features (62 total): modified residue 16, helix 13, strand 9, binding site 6, mutagenesis site 5, compositionally biased region 3, sequence variant 2, turn 2, chain 1, domain 1, region of interest 1, splice variant 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

29 structures.

PDB	Method	Resolution (Å)
8BJU	X-RAY DIFFRACTION	1.53
9D0S	X-RAY DIFFRACTION	1.64
9TG7	X-RAY DIFFRACTION	1.68
1X8B	X-RAY DIFFRACTION	1.81
5VD8	X-RAY DIFFRACTION	1.85
5VD9	X-RAY DIFFRACTION	1.87
2IN6	X-RAY DIFFRACTION	1.9
5V5Y	X-RAY DIFFRACTION	1.9
5VC5	X-RAY DIFFRACTION	1.93
9D0Q	X-RAY DIFFRACTION	1.96
5VC3	X-RAY DIFFRACTION	1.97
5VC6	X-RAY DIFFRACTION	2
5VD4	X-RAY DIFFRACTION	2.02
5VD2	X-RAY DIFFRACTION	2.05
5VD5	X-RAY DIFFRACTION	2.05
5VD7	X-RAY DIFFRACTION	2.08
5VC4	X-RAY DIFFRACTION	2.1
5VDA	X-RAY DIFFRACTION	2.1
2IO6	X-RAY DIFFRACTION	2.2
3BI6	X-RAY DIFFRACTION	2.2
3BIZ	X-RAY DIFFRACTION	2.2
2Z2W	X-RAY DIFFRACTION	2.22
3CR0	X-RAY DIFFRACTION	2.3
9D0R	X-RAY DIFFRACTION	2.34
3CQE	X-RAY DIFFRACTION	2.5
7N3U	X-RAY DIFFRACTION	2.65
9R55	X-RAY DIFFRACTION	2.67
9R56	X-RAY DIFFRACTION	3.01
8WDK	ELECTRON MICROSCOPY	3.64

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P30291-F1	65.90	0.37

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 426 (proton acceptor)

Ligand- & substrate-binding residues (6): 431; 463; 465; 305–313; 328; 342

Post-translational modifications (16): 53, 78, 85, 123, 127, 137, 139, 150, 165, 187, 190, 239, 270, 307, 312, 642

Mutagenesis-validated functional residues (5):

Position	Phenotype
53	abolishes phosphorylation by plk1 and cdk1 and binding of the scf(btrc) complex, leading to stabilization of the protein
116–117	impairs binding of the scf(btrc) complex.
123	abolishes phosphorylation by plk1 and cdk1 and binding of the scf(btrc) complex, leading to stabilization of the protein
328	abolishes activity.
642	abolishes phosphorylation by brsk1 and brsk2.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-156711	Polo-like kinase mediated events
R-HSA-69202	Cyclin E associated events during G1/S transition
R-HSA-69273	Cyclin A/B1/B2 associated events during G2/M transition
R-HSA-69478	G2/M DNA replication checkpoint
R-HSA-69656	Cyclin A:Cdk2-associated events at S phase entry
R-HSA-75035	Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex
R-HSA-983231	Factors involved in megakaryocyte development and platelet production

MSigDB gene sets: 454 (showing top): E2F_Q4, AGGAAGC_MIR5163P, SA_G2_AND_M_PHASES, MODULE_52, E2F_Q4_01, GOBP_POSITIVE_REGULATION_OF_DNA_REPLICATION, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, FREAC2_01, BROWNE_HCMV_INFECTION_6HR_DN, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, TGCACTT_MIR519C_MIR519B_MIR519A, CROONQUIST_NRAS_SIGNALING_DN, REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT

GO Biological Process (13): G2/M transition of mitotic cell cycle (GO:0000086), microtubule cytoskeleton organization (GO:0000226), negative regulation of G2/M transition of mitotic cell cycle (GO:0010972), establishment of cell polarity (GO:0030010), positive regulation of DNA replication (GO:0045740), neuron projection morphogenesis (GO:0048812), cell division (GO:0051301), negative regulation of G1/S transition of mitotic cell cycle (GO:2000134), mitotic cell cycle (GO:0000278), protein phosphorylation (GO:0006468), nuclear envelope organization (GO:0006998), mitotic nuclear membrane disassembly (GO:0007077), positive regulation of G2/M transition of mitotic cell cycle (GO:0010971)

GO Molecular Function (10): magnesium ion binding (GO:0000287), protein tyrosine kinase activity (GO:0004713), non-membrane spanning protein tyrosine kinase activity (GO:0004715), ATP binding (GO:0005524), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
G2/M Transition	2
G1/S Transition	1
G2/M Checkpoints	1
S Phase	1
G2/M DNA damage checkpoint	1
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitotic cell cycle	2
G2/M transition of mitotic cell cycle	2
regulation of G2/M transition of mitotic cell cycle	2
negative regulation of mitotic cell cycle phase transition	2
nuclear lumen	2
cellular anatomical structure	2
mitotic cell cycle phase transition	1
cell cycle G2/M phase transition	1
cytoskeleton organization	1
microtubule-based process	1
negative regulation of cell cycle G2/M phase transition	1
establishment or maintenance of cell polarity	1
DNA replication	1
regulation of DNA replication	1
positive regulation of DNA metabolic process	1
neuron projection development	1
plasma membrane bounded cell projection morphogenesis	1
cellular process	1
G1/S transition of mitotic cell cycle	1
negative regulation of cell cycle G1/S phase transition	1
regulation of G1/S transition of mitotic cell cycle	1
cell cycle	1
mitotic nuclear division	1
phosphorylation	1
protein modification process	1
nucleus organization	1
endomembrane system organization	1
membrane organization	1
nuclear membrane disassembly	1
mitotic cell cycle process	1
positive regulation of mitotic cell cycle phase transition	1
positive regulation of cell cycle G2/M phase transition	1
metal ion binding	1
protein kinase activity	1
protein tyrosine kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1

Protein interactions and networks

STRING

2732 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WEE1	CDK1	P06493	958
WEE1	CCNB1	P14635	932
WEE1	PLK1	P53350	926
WEE1	CDC25C	P30307	894
WEE1	CHEK1	O14757	861
WEE1	CDCA3	Q99618	845
WEE1	CDC25A	P30304	831
WEE1	CDC25B	P30305	811
WEE1	CCNL2	Q96S94	808
WEE1	CDK2	P24941	800
WEE1	ATM	Q13315	766
WEE1	CCNA1	P78396	765
WEE1	BTRC	Q9Y297	753
WEE1	HSP90AB1	P08238	753
WEE1	TP53	P04637	745

IntAct

97 interactions, top by confidence:

A	B	Type	Score
YWHAB	PIK3C2A	psi-mi:“MI:0914”(association)	0.800
YWHAB	WEE1	psi-mi:“MI:0915”(physical association)	0.800
WEE1	YWHAB	psi-mi:“MI:0915”(physical association)	0.800
YEATS4	ZNHIT1	psi-mi:“MI:0914”(association)	0.790
WEE1	YWHAZ	psi-mi:“MI:0915”(physical association)	0.730
YWHAZ	WEE1	psi-mi:“MI:0915”(physical association)	0.730
YWHAZ	WEE1	psi-mi:“MI:0407”(direct interaction)	0.730
SFN	WEE1	psi-mi:“MI:0915”(physical association)	0.670
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
FBXW11	WEE1	psi-mi:“MI:2364”(proximity)	0.600
FBXW11	WEE1	psi-mi:“MI:0914”(association)	0.600
WEE1	FBXW11	psi-mi:“MI:0915”(physical association)	0.600
WEE1	PLK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.590
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAZ	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
PLK1	C1orf226	psi-mi:“MI:0914”(association)	0.560
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
YEATS4	ACTL6B	psi-mi:“MI:0914”(association)	0.530
BTRC	WEE1	psi-mi:“MI:0914”(association)	0.500
WEE1	BTRC	psi-mi:“MI:0915”(physical association)	0.500
WEE1	BRAF	psi-mi:“MI:2364”(proximity)	0.470
BRAF	WEE1	psi-mi:“MI:0915”(physical association)	0.470
WEE1	H2BC21	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
WEE1		psi-mi:“MI:0217”(phosphorylation reaction)	0.440

BioGRID (202): WEE1 (Affinity Capture-MS), CNBP (Affinity Capture-MS), EEF2 (Affinity Capture-MS), PCBP1 (Affinity Capture-MS), SPTBN1 (Affinity Capture-MS), WEE1 (Affinity Capture-MS), WEE1 (Affinity Capture-MS), WEE1 (Proximity Label-MS), WEE1 (Proximity Label-MS), WEE1 (Proximity Label-MS), WEE1 (Affinity Capture-MS), RUSC2 (Affinity Capture-MS), CEP350 (Affinity Capture-MS), WDFY3 (Affinity Capture-MS), BRPF3 (Affinity Capture-MS)

ESM2 similar proteins: A2AKB9, A2RRH5, A2RRU4, A2SXS5, A6QM06, O60346, O88559, P30291, P97260, Q08BB3, Q0P5I0, Q12770, Q3B7L5, Q3MHH0, Q3UHE1, Q4R3J7, Q5E9I8, Q5FW06, Q5M9G8, Q5MNU5, Q5QP82, Q5R7H5, Q5T6F0, Q5VW00, Q5ZJL7, Q63ZP7, Q69Z89, Q6AX81, Q6GQT6, Q6NS60, Q6NWH1, Q6P809, Q6ZWB6, Q8AVS9, Q8BGW4, Q8BGZ3, Q8CHE4, Q8NHY2, Q8QZS3, Q8TEB1

Diamond homologs: A4K2Q5, A4K2S1, A4PES0, A4QNA8, A5D791, D2HHP1, E1BTE1, E2RSS3, F4I1N8, O02827, O13148, O13889, O18209, O22042, O57473, O80397, P07527, P0C1S8, P11799, P15442, P27636, P29294, P30291, P32581, P33279, P47810, P47817, P54350, P54737, Q15746, Q1LX51, Q28824, Q4R8E0, Q54E34, Q54F40, Q54JQ1, Q54RP7, Q54ZN3, Q558U1, Q55F45

SIGNOR signaling

35 interactions.

A	Effect	B	Mechanism
PAK1	down-regulates	WEE1	phosphorylation
CDK1	down-regulates	WEE1	phosphorylation
PLK1	down-regulates	WEE1	phosphorylation
BTRC	down-regulates	WEE1	binding
CDK2	down-regulates	WEE1	phosphorylation
WEE1	down-regulates	CDK1	phosphorylation
CHEK1	up-regulates	WEE1	phosphorylation
1-[6-(2-hydroxypropan-2-yl)-2-pyridinyl]-6-[4-(4-methyl-1-piperazinyl)anilino]-2-prop-2-enyl-3-pyrazolo[3,4-d]pyrimidinone	down-regulates	WEE1	“chemical inhibition”
SCF-betaTRCP	down-regulates	WEE1	binding
AR	“down-regulates quantity by repression”	WEE1	“transcriptional regulation”
PPP2R2A	“up-regulates quantity by stabilization”	WEE1	dephosphorylation
CDC14A	“up-regulates quantity by stabilization”	WEE1	dephosphorylation
CSNK2A1	“down-regulates quantity by destabilization”	WEE1	phosphorylation
CDK2	“down-regulates quantity by destabilization”	WEE1
PLK1	“down-regulates quantity by destabilization”	WEE1	phosphorylation
CTDP1	“up-regulates activity”	WEE1	dephosphorylation
WEE1	“down-regulates quantity by destabilization”	ERG	phosphorylation
WEE1	“down-regulates activity”	PTP4A1	phosphorylation
CHEK1	“up-regulates activity”	WEE1	phosphorylation
NIM1K	“down-regulates activity”	WEE1	phosphorylation
WEE1	“down-regulates activity”	PLRG1	phosphorylation
WEE1	down-regulates	CDK2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 66 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	8	112.8×	3e-13
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	8	99.5×	6e-13
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	87.1×	5e-11
Activation of BH3-only proteins	8	73.6×	8e-12
Intrinsic Pathway for Apoptosis	8	43.4×	5e-10
RHO GTPases activate PKNs	7	41.1×	1e-08
FOXO-mediated transcription	6	37.3×	3e-07
G2/M Checkpoints	11	27.4×	1e-11

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	6	36.0×	5e-06
epidermal growth factor receptor signaling pathway	5	20.3×	1e-03
regulation of protein localization	5	16.9×	1e-03
intracellular protein localization	9	15.4×	5e-06
protein phosphorylation	10	11.1×	5e-06
regulation of cell cycle	6	7.3×	9e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	8	6.8×	2e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

71 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	65
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1500 predictions. Top by Δscore:

Variant	Effect	Δscore
11:9575886:A:AG	acceptor_gain	1.0000
11:9575887:G:GG	acceptor_gain	1.0000
11:9575887:GA:G	acceptor_gain	1.0000
11:9575887:GAGT:G	acceptor_gain	1.0000
11:9575887:GAGTT:G	acceptor_gain	1.0000
11:9576088:GAA:G	donor_gain	1.0000
11:9576090:ATGA:A	donor_gain	1.0000
11:9576091:TGA:T	donor_gain	1.0000
11:9576092:GA:G	donor_gain	1.0000
11:9576092:GAG:G	donor_gain	1.0000
11:9576094:G:GG	donor_gain	1.0000
11:9576095:T:A	donor_loss	1.0000
11:9576226:TTA:T	acceptor_loss	1.0000
11:9576228:A:AG	acceptor_gain	1.0000
11:9576228:AGTT:A	acceptor_loss	1.0000
11:9576229:G:GC	acceptor_gain	1.0000
11:9576229:GT:G	acceptor_gain	1.0000
11:9576229:GTT:G	acceptor_gain	1.0000
11:9576229:GTTC:G	acceptor_gain	1.0000
11:9576229:GTTCC:G	acceptor_gain	1.0000
11:9576291:AAGGT:A	donor_loss	1.0000
11:9576292:AGG:A	donor_loss	1.0000
11:9576293:GGTAA:G	donor_loss	1.0000
11:9576294:G:GG	donor_gain	1.0000
11:9576295:T:A	donor_loss	1.0000
11:9576462:T:G	acceptor_gain	1.0000
11:9576486:GA:G	acceptor_gain	1.0000
11:9576486:GAGA:G	acceptor_gain	1.0000
11:9576655:GATGA:G	donor_gain	1.0000
11:9576656:A:G	donor_gain	1.0000

AlphaMissense

4213 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:9576019:T:A	N236K	1.000
11:9576019:T:G	N236K	1.000
11:9576023:T:C	F238L	1.000
11:9576025:T:A	F238L	1.000
11:9576025:T:G	F238L	1.000
11:9576535:T:C	F299L	1.000
11:9576535:T:G	F299V	1.000
11:9576536:T:C	F299S	1.000
11:9576536:T:G	F299C	1.000
11:9576537:T:A	F299L	1.000
11:9576537:T:G	F299L	1.000
11:9576563:G:A	G308E	1.000
11:9576568:T:C	F310L	1.000
11:9576570:T:A	F310L	1.000
11:9576570:T:G	F310L	1.000
11:9576571:G:C	G311R	1.000
11:9576572:G:A	G311D	1.000
11:9576578:T:A	V313E	1.000
11:9576586:T:C	C316R	1.000
11:9576587:G:A	C316Y	1.000
11:9576588:T:G	C316W	1.000
11:9576601:G:C	D321H	1.000
11:9576602:A:T	D321V	1.000
11:9576604:G:A	G322R	1.000
11:9576604:G:C	G322R	1.000
11:9576605:G:A	G322E	1.000
11:9576605:G:T	G322V	1.000
11:9576613:T:G	Y325D	1.000
11:9576616:G:C	A326P	1.000
11:9576617:C:A	A326D	1.000

dbSNP variants (sampled 300 via entrez): RS1000025321 (11:9577851 A>G), RS1000062488 (11:9576655 G>A), RS1000202111 (11:9583965 C>A,T), RS1000249893 (11:9572126 A>C), RS1000435073 (11:9577053 A>C,G), RS1000550485 (11:9589599 G>C,T), RS1000740651 (11:9588865 T>G), RS1000808583 (11:9590304 C>A,T), RS1001069917 (11:9589298 T>G), RS1001149076 (11:9577568 A>G), RS1001257110 (11:9577372 T>A,C), RS1001886930 (11:9583126 A>G), RS1001946623 (11:9589976 C>T), RS1001956842 (11:9582727 C>T), RS1002092662 (11:9582973 C>T)

Disease associations

OMIM: gene MIM:193525 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST008477_8	Emphysema annual change measurement in smokers (adjusted lung density)	3.000000e-06
GCST010148_16	Cutaneous squamous cell carcinoma	9.000000e-12
GCST90002401_177	Platelet distribution width	1.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007626	emphysema imaging measurement
EFO:1001927	cutaneous squamous cell carcinoma
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL4630732 (PROTEIN-PROTEIN INTERACTION), CHEMBL5169067 (PROTEIN-PROTEIN INTERACTION), CHEMBL5491 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

27 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 138,354 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL180022	NERATINIB	4	9,404
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3348923	TOVORAFENIB	4	834
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL1233528	VOLASERTIB	3	1,511
CHEMBL3137331	DEFACTINIB	3	1,229
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1976040	ADAVOSERTIB	2	1,738
CHEMBL1721885	SU-014813	2	363
CHEMBL475251	R-406	2	762
CHEMBL5095036	AZENOSERTIB	2	211
CHEMBL5199076	LUNRESERTIB	2	34
CHEMBL564829	MILCICLIB	2	821
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL574737	UCN-01	2	2,217
CHEMBL587723	AEE-788	2
CHEMBL607707	PELITINIB	2
CHEMBL1908397	KW-2449	1
CHEMBL3128043	PF-03758309	1
CHEMBL4289017	PF-03814735	1
CHEMBL482967	CYC-116	1
CHEMBL49120	PD-0166285	1

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
WEE1 RS3910384	Platinum Compound + Gemcitabine	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID814

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — WEE family

Most potent curated ligand interactions (5 total), top 5:

Ligand	Action	Affinity	Parameter
BMS-986463	Binding	9.0	pEC50
compound 23f [Zhang et al., 2025]	Inhibition	8.92	pIC50
azenosertib	Inhibition	8.41	pIC50
adavosertib	Inhibition	8.29	pIC50
PD166285	Inhibition	7.62	pIC50

Binding affinities (BindingDB)

35 measured of 66 human assays (66 total across all organisms); most potent 35 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Staurosporine	KD	1.7 nM
1-(7-hydroxy-7-methylspiro[5H-cyclopenta[b]pyridine-6,1’-cyclopropane]-2-yl)-6-[4-(4-methylpiperazin-1-yl)anilino]-2-prop-2-enylpyrazolo[3,4-d]pyrimidin-3-one	IC50	7.5 nM	US-20250304587: WEE1 INHIBITOR, PREPARATION THEREFOR AND USE THEREOF
1-[(8S)-8-hydroxy-8-methylspiro[5,6-dihydroquinoline-7,1’-cyclopropane]-2-yl]-6-[4-(6-methyl-3,6-diazabicyclo[3.1.1]heptan-3-yl)anilino]-2-prop-2-enylpyrazolo[3,4-d]pyrimidin-3-one	IC50	7.5 nM	US-20250304587: WEE1 INHIBITOR, PREPARATION THEREFOR AND USE THEREOF
1-[7-hydroxy-7-(trifluoromethyl)spiro[5H-cyclopenta[b]pyridine-6,1’-cyclopropane]-2-yl]-6-[4-(4-methylpiperazin-1-yl)anilino]-2-prop-2-enylpyrazolo[3,4-d]pyrimidin-3-one	IC50	7.5 nM	US-20250304587: WEE1 INHIBITOR, PREPARATION THEREFOR AND USE THEREOF
1-[(8S)-8-deuterio-8-hydroxyspiro[5,6-dihydroquinoline-7,1’-cyclopropane]-2-yl]-6-[4-(9-methyl-3,9-diazaspiro[5.5]undecan-3-yl)anilino]-2-prop-2-enylpyrazolo[3,4-d]pyrimidin-3-one	IC50	7.5 nM	US-20250304587: WEE1 INHIBITOR, PREPARATION THEREFOR AND USE THEREOF
1-[(8R)-8-deuterio-8-hydroxyspiro[5,6-dihydroquinoline-7,1’-cyclopropane]-2-yl]-6-[4-(9-methyl-3,9-diazaspiro[5.5]undecan-3-yl)anilino]-2-prop-2-enylpyrazolo[3,4-d]pyrimidin-3-one	IC50	7.5 nM	US-20250304587: WEE1 INHIBITOR, PREPARATION THEREFOR AND USE THEREOF
1-[(8R)-8-deuterio-8-hydroxyspiro[5,6-dihydroquinoline-7,1’-cyclopropane]-2-yl]-6-[4-(6-propan-2-yl-3,6-diazabicyclo[3.1.1]heptan-3-yl)anilino]-2-prop-2-enylpyrazolo[3,4-d]pyrimidin-3-one	IC50	7.5 nM	US-20250304587: WEE1 INHIBITOR, PREPARATION THEREFOR AND USE THEREOF
6-[4-[(3aS,6aR)-2-methyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]anilino]-1-[(8R)-8-hydroxy-8-(trifluoromethyl)-6,7-dihydro-5H-quinolin-2-yl]-2-prop-2-enylpyrazolo[3,4-d]pyrimidin-3-one	IC50	7.5 nM	US-20250304587: WEE1 INHIBITOR, PREPARATION THEREFOR AND USE THEREOF
1-[(8R)-8-deuterio-8-hydroxyspiro[5,6-dihydroquinoline-7,1’-cyclopropane]-2-yl]-6-[3-methyl-4-(9-methyl-3,9-diazaspiro[5.5]undecan-3-yl)anilino]-2-prop-2-enylpyrazolo[3,4-d]pyrimidin-3-one	IC50	7.5 nM	US-20250304587: WEE1 INHIBITOR, PREPARATION THEREFOR AND USE THEREOF
6-[4-[4-(dimethylamino)piperidin-1-yl]anilino]-1-[(8S)-8-hydroxy-8-methylspiro[5,6-dihydroquinoline-7,1’-cyclopropane]-2-yl]-2-prop-2-enylpyrazolo[3,4-d]pyrimidin-3-one	IC50	7.5 nM	US-20250304587: WEE1 INHIBITOR, PREPARATION THEREFOR AND USE THEREOF
1-[(8R)-8-hydroxyspiro[6,8-dihydro-5H-quinoline-7,1’-cyclopropane]-2-yl]-6-[4-(9-methyl-3,9-diazaspiro[5.5]undecan-3-yl)anilino]-2-prop-2-enylpyrazolo[3,4-d]pyrimidin-3-one	IC50	7.5 nM	US-20250304587: WEE1 INHIBITOR, PREPARATION THEREFOR AND USE THEREOF
BMS-354825	KD	27 nM
Azenosertib	IC50	55 nM	US-20250304587: WEE1 INHIBITOR, PREPARATION THEREFOR AND USE THEREOF
1’-ethyl-6’-[6-[4-(4-methylpiperazin-1-yl)anilino]-3-oxo-2-prop-2-enylpyrazolo[3,4-d]pyrimidin-1-yl]spiro[cyclopropane-1,3’-indole]-2’-one	IC50	55 nM	US-20250304587: WEE1 INHIBITOR, PREPARATION THEREFOR AND USE THEREOF
1’-ethyl-6’-[6-[4-(4-methylpiperazin-1-yl)anilino]-3-oxo-2-prop-2-enylpyrazolo[3,4-d]pyrimidin-1-yl]spiro[cyclobutane-1,3’-pyrrolo[2,3-b]pyridine]-2’-one	IC50	55 nM	US-20250304587: WEE1 INHIBITOR, PREPARATION THEREFOR AND USE THEREOF
6-(2,6-Dichlorophenyl)-2-((4-(piperazin-1-yl)phenyl)amino)pyrido[4,3-d]pyrimidin-5(6H)-one	IC50	105 nM	US-9714244: Substituted pyrido[4,3-d]pyrimidines as Wee-1 inhibitors
6-(2,6-Dichlorophenyl)-2-((4-(2-(diethylamino)ethoxy)phenyl)amino)pyrido[4,3-d]pyrimidin-5(6H)-one	IC50	105 nM	US-9714244: Substituted pyrido[4,3-d]pyrimidines as Wee-1 inhibitors
2-((4-(4-Acetylpiperazin-1-yl)phenyl)amino)-6-(2,6-dichlorophenyl)pyrido[4,3-d]pyrimidin-5(6H)-one	IC50	105 nM	US-9714244: Substituted pyrido[4,3-d]pyrimidines as Wee-1 inhibitors
6-(2,6-Dichlorophenyl)-2-((4-(1,1-dioxidothiomorpholino)phenyl)amino)pyrido[4,3-d]pyrimidin-5(6H)-one	IC50	105 nM	US-9714244: Substituted pyrido[4,3-d]pyrimidines as Wee-1 inhibitors
6-(2,6-Dichlorophenyl)-2-((3-methyl-4-(piperazin-1-yl)phenyl)amino)pyrido[4,3-d]pyrimidin-5(6H)-one	IC50	105 nM	US-9714244: Substituted pyrido[4,3-d]pyrimidines as Wee-1 inhibitors
6-(2,6-Dichlorophenyl)-2-((4-(1-methylpiperidin-4-yl)phenyl)amino)pyrido[4,3-d]pyrimidin-5(6H)-one, HCl	IC50	105 nM	US-9714244: Substituted pyrido[4,3-d]pyrimidines as Wee-1 inhibitors
6-(2,6-Dichlorophenyl)-2-((4-(2-(dimethylamino)ethyl)phenyl)amino)pyrido[4,3-d]pyrimidin-5(6H)-one, HCl	IC50	105 nM	US-9714244: Substituted pyrido[4,3-d]pyrimidines as Wee-1 inhibitors
6-(2,6-Dichlorophenyl)-2-((3-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)pyrido[4,3-d]pyrimidin-5(6H)-one, HCl	IC50	105 nM	US-9714244: Substituted pyrido[4,3-d]pyrimidines as Wee-1 inhibitors
6-(2,6-Dichlorophenyl)-2-((4-(4-methylpiperazin-1-yl)phenyl)amino)pyrido[4,3-d]pyrimidin-5(6H)-one	IC50	105 nM	US-9714244: Substituted pyrido[4,3-d]pyrimidines as Wee-1 inhibitors
6-(2,6-Dichlorophenyl)-2-((4-(4-isopropylpiperazin-1-yl)phenyl)amino)pyrido[4,3-d]pyrimidin-5(6H)-one	IC50	105 nM	US-9714244: Substituted pyrido[4,3-d]pyrimidines as Wee-1 inhibitors
2-((3-(Aminomethyl)phenyl)amino)-6-(2,6-dichlorophenyl)pyrido[4,3-d]pyrimidin-5(6H)-one	IC50	105 nM	US-9714244: Substituted pyrido[4,3-d]pyrimidines as Wee-1 inhibitors
6-(2,6-Dichlorophenyl)-2-((3-(4-methylpiperazin-1-yl)phenyl)amino)pyrido[4,3-d]pyrimidin-5(6H)-one	IC50	105 nM	US-9714244: Substituted pyrido[4,3-d]pyrimidines as Wee-1 inhibitors
6-(2,6-Dichlorophenyl)-2-((3,5-difluoro-4-(piperazin-1-yl)phenyl)amino)pyrido[4,3-d]pyrimidin-5(6H)-one	IC50	105 nM	US-9714244: Substituted pyrido[4,3-d]pyrimidines as Wee-1 inhibitors
6-(2,6-Dichlorophenyl)-2-((6-(4-methylpiperazin-1-yl)pyridin-3-yl)amino)pyrido[4,3-d]pyrimidin-5(6H)-one	IC50	105 nM	US-9714244: Substituted pyrido[4,3-d]pyrimidines as Wee-1 inhibitors
6-(2,6-Dichlorophenyl)-2-((4-(4-methylpiperazine-1-carbonyl)phenyl)amino)pyrido[4,3-d]pyrimidin-5(6H)-one	IC50	105 nM	US-9714244: Substituted pyrido[4,3-d]pyrimidines as Wee-1 inhibitors
2-(4-(4-((6-(2,6-Dichlorophenyl)-5-oxo-5,6-dihydropyrido[4,3-d]pyrimidin-2-yl)amino)phenyl)piperazin-1-yl)acetic acid	IC50	105 nM	US-9714244: Substituted pyrido[4,3-d]pyrimidines as Wee-1 inhibitors
N-[4-({4-[(3-methyl-1H-pyrazol-5-yl)amino]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl}sulfanyl)phenyl]cyclopropanecarboxamide	KD	1100 nM
5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamide	KD	2600 nM
(E)-N-[4-(3-chloro-4-fluoro-anilino)-3-cyano-7-ethoxy-6-quinolyl]-4-(dimethylamino)but-2-enamide	KD	3500 nM
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	KD	3500 nM

ChEMBL bioactivities

1607 potent at pChembl≥5 of 1652 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	IC50	0.1	nM	CHEMBL5278196
10.00	IC50	0.1	nM	CHEMBL5876377
10.00	IC50	0.1	nM	CHEMBL5831450
10.00	IC50	0.1	nM	CHEMBL5933715
9.70	Ki	0.2	nM	CHEMBL4562919
9.70	Ki	0.2	nM	CHEMBL4544916
9.70	Ki	0.2	nM	CHEMBL4441166
9.70	Ki	0.2	nM	CHEMBL4454675
9.70	IC50	0.2	nM	CHEMBL5284925
9.70	IC50	0.2	nM	CHEMBL6065998
9.70	IC50	0.2	nM	CHEMBL5963536
9.70	IC50	0.2	nM	CHEMBL5759393
9.70	IC50	0.2	nM	CHEMBL5956499
9.60	Ki	0.2512	nM	CHEMBL379975
9.52	Ki	0.3	nM	CHEMBL4443172
9.52	Ki	0.3	nM	CHEMBL4554796
9.52	Ki	0.3	nM	CHEMBL4444364
9.52	Ki	0.3	nM	CHEMBL4529353
9.52	IC50	0.3	nM	CHEMBL5824691
9.52	IC50	0.3	nM	CHEMBL6017706
9.52	IC50	0.3	nM	CHEMBL5761564
9.52	IC50	0.3	nM	CHEMBL5807524
9.52	IC50	0.3	nM	CHEMBL5825861
9.52	IC50	0.3	nM	CHEMBL5765325
9.52	IC50	0.3	nM	CHEMBL6172478
9.40	IC50	0.4	nM	CHEMBL5987402
9.40	IC50	0.4	nM	CHEMBL5876812
9.40	IC50	0.4	nM	CHEMBL5824402
9.40	IC50	0.4	nM	CHEMBL5805001
9.40	IC50	0.4	nM	CHEMBL5820379
9.40	IC50	0.4	nM	CHEMBL5934516
9.40	IC50	0.4	nM	CHEMBL5840405
9.40	IC50	0.4	nM	CHEMBL5927192
9.40	IC50	0.4	nM	CHEMBL5951237
9.40	IC50	0.4	nM	CHEMBL5775083
9.40	IC50	0.4	nM	CHEMBL5922763
9.38	IC50	0.42	nM	CHEMBL5279054
9.30	Ki	0.5	nM	CHEMBL4526423
9.30	IC50	0.5	nM	CHEMBL5776570
9.30	IC50	0.5	nM	CHEMBL5906316
9.30	IC50	0.5	nM	CHEMBL6031701
9.30	IC50	0.5	nM	CHEMBL5778248
9.30	IC50	0.5	nM	CHEMBL5921620
9.30	IC50	0.5	nM	CHEMBL5840313
9.30	IC50	0.5	nM	CHEMBL6010715
9.30	Ki	0.5012	nM	PD-0166285
9.29	IC50	0.51	nM	CHEMBL5269524
9.29	IC50	0.51	nM	CHEMBL5282382
9.25	IC50	0.56	nM	ADAVOSERTIB
9.24	IC50	0.57	nM	CHEMBL5284989

PubChem BioAssay actives

1005 with measured affinity, of 1831 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[6-[6-ethyl-2-[4-(4-methylpiperazin-1-yl)anilino]pyrrolo[2,3-d]pyrimidin-7-yl]-2-pyridinyl]propan-2-ol	1921871: Inhibition of Wee1 (unknown origin) incubated for 60 mins by LanthaScreen Eu-Kinase binding assay	ic50	0.0001	uM
7-[6-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]-2-pyridinyl]-6-ethyl-N-[4-(4-methylpiperazin-1-yl)phenyl]pyrrolo[2,3-d]pyrimidin-2-amine	1921871: Inhibition of Wee1 (unknown origin) incubated for 60 mins by LanthaScreen Eu-Kinase binding assay	ic50	0.0002	uM
6-(2,6-dichlorophenyl)-2-[4-(4-methylpiperazin-1-yl)anilino]-8-phenylpyrido[2,3-d]pyrimidin-5-one	1589875: Binding affinity to wild type N-terminal GST-tagged human WEE1 catalytic domain (215 to 646 residues) expressed in baculovirus expression system measured after 1 hr by TR-FRET assay	ki	0.0002	uM
6-(2,6-dichlorophenyl)-8-(2-hydroxy-2-methylpropyl)-2-[4-(4-methylpiperazin-1-yl)anilino]pyrido[2,3-d]pyrimidin-5-one	1589875: Binding affinity to wild type N-terminal GST-tagged human WEE1 catalytic domain (215 to 646 residues) expressed in baculovirus expression system measured after 1 hr by TR-FRET assay	ki	0.0002	uM
6-(2,6-dichlorophenyl)-8-methyl-2-[(2-methylspiro[1,3-dihydroisoquinoline-4,1’-cyclopropane]-7-yl)amino]pyrido[2,3-d]pyrimidin-5-one	1589875: Binding affinity to wild type N-terminal GST-tagged human WEE1 catalytic domain (215 to 646 residues) expressed in baculovirus expression system measured after 1 hr by TR-FRET assay	ki	0.0002	uM
8-cyclopropyl-6-(2,6-dichlorophenyl)-2-[(2-methylspiro[1,3-dihydroisoquinoline-4,1’-cyclopropane]-7-yl)amino]pyrido[2,3-d]pyrimidin-5-one	1589875: Binding affinity to wild type N-terminal GST-tagged human WEE1 catalytic domain (215 to 646 residues) expressed in baculovirus expression system measured after 1 hr by TR-FRET assay	ki	0.0002	uM
6-(2,6-dichlorophenyl)-8-methyl-2-[4-(4-methylpiperazin-1-yl)anilino]pyrido[2,3-d]pyrimidin-5-one	1589875: Binding affinity to wild type N-terminal GST-tagged human WEE1 catalytic domain (215 to 646 residues) expressed in baculovirus expression system measured after 1 hr by TR-FRET assay	ki	0.0003	uM
6-(2,6-dichlorophenyl)-8-ethenyl-2-[(2-methylspiro[1,3-dihydroisoquinoline-4,1’-cyclopropane]-7-yl)amino]pyrido[4,3-d]pyrimidin-5-one	1589875: Binding affinity to wild type N-terminal GST-tagged human WEE1 catalytic domain (215 to 646 residues) expressed in baculovirus expression system measured after 1 hr by TR-FRET assay	ki	0.0003	uM
6-(2,6-dichlorophenyl)-8-(hydroxymethyl)-2-[(2-methylspiro[1,3-dihydroisoquinoline-4,1’-cyclopropane]-7-yl)amino]pyrido[4,3-d]pyrimidin-5-one	1589875: Binding affinity to wild type N-terminal GST-tagged human WEE1 catalytic domain (215 to 646 residues) expressed in baculovirus expression system measured after 1 hr by TR-FRET assay	ki	0.0003	uM
6-(2,6-dichlorophenyl)-8-ethyl-2-[(2-methylspiro[1,3-dihydroisoquinoline-4,1’-cyclopropane]-7-yl)amino]pyrido[2,3-d]pyrimidin-5-one	1589875: Binding affinity to wild type N-terminal GST-tagged human WEE1 catalytic domain (215 to 646 residues) expressed in baculovirus expression system measured after 1 hr by TR-FRET assay	ki	0.0003	uM
2-[6-[2-[4-(4-methylpiperazin-1-yl)anilino]-6-propan-2-ylpyrrolo[2,3-d]pyrimidin-7-yl]-2-pyridinyl]propan-2-ol	1921871: Inhibition of Wee1 (unknown origin) incubated for 60 mins by LanthaScreen Eu-Kinase binding assay	ic50	0.0004	uM
7-[6-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]-2-pyridinyl]-6-methyl-N-[4-(4-methylpiperazin-1-yl)phenyl]pyrrolo[2,3-d]pyrimidin-2-amine	1921871: Inhibition of Wee1 (unknown origin) incubated for 60 mins by LanthaScreen Eu-Kinase binding assay	ic50	0.0005	uM
6-cyclopropyl-7-[6-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]-2-pyridinyl]-N-[3-fluoro-4-(4-methylpiperazin-1-yl)phenyl]pyrrolo[2,3-d]pyrimidin-2-amine	1921871: Inhibition of Wee1 (unknown origin) incubated for 60 mins by LanthaScreen Eu-Kinase binding assay	ic50	0.0005	uM
6-(2,6-dichlorophenyl)-8-methyl-2-[(2-methylspiro[1,3-dihydroisoquinoline-4,1’-cyclopropane]-7-yl)amino]pyrido[4,3-d]pyrimidin-5-one	1589875: Binding affinity to wild type N-terminal GST-tagged human WEE1 catalytic domain (215 to 646 residues) expressed in baculovirus expression system measured after 1 hr by TR-FRET assay	ki	0.0005	uM
2-[6-[6-methyl-2-[4-(4-methylpiperazin-1-yl)anilino]pyrrolo[2,3-d]pyrimidin-7-yl]-2-pyridinyl]propan-2-ol	1921871: Inhibition of Wee1 (unknown origin) incubated for 60 mins by LanthaScreen Eu-Kinase binding assay	ic50	0.0006	uM
7-[6-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]-2-pyridinyl]-5-fluoro-N-[4-(4-methylpiperazin-1-yl)phenyl]-6-propylpyrrolo[2,3-d]pyrimidin-2-amine	1921871: Inhibition of Wee1 (unknown origin) incubated for 60 mins by LanthaScreen Eu-Kinase binding assay	ic50	0.0006	uM
1-[6-(2-hydroxypropan-2-yl)-2-pyridinyl]-6-[4-(4-methylpiperazin-1-yl)anilino]-2-prop-2-enylpyrazolo[3,4-d]pyrimidin-3-one	1921871: Inhibition of Wee1 (unknown origin) incubated for 60 mins by LanthaScreen Eu-Kinase binding assay	ic50	0.0006	uM
6-(2,6-dichlorophenyl)-2-[(2-methylspiro[1,3-dihydroisoquinoline-4,1’-cyclopropane]-7-yl)amino]-8H-pyrido[2,3-d]pyrimidin-5-one	1589875: Binding affinity to wild type N-terminal GST-tagged human WEE1 catalytic domain (215 to 646 residues) expressed in baculovirus expression system measured after 1 hr by TR-FRET assay	ki	0.0006	uM
6-(2,6-dichlorophenyl)-8-(difluoromethyl)-2-[(2-methylspiro[1,3-dihydroisoquinoline-4,1’-cyclopropane]-7-yl)amino]pyrido[4,3-d]pyrimidin-5-one	1589875: Binding affinity to wild type N-terminal GST-tagged human WEE1 catalytic domain (215 to 646 residues) expressed in baculovirus expression system measured after 1 hr by TR-FRET assay	ki	0.0006	uM
6-(2,6-dichlorophenyl)-8-methyl-2-[3-methyl-4-(1-methylpiperidin-4-yl)anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one	2066595: Inhibition of WEE1 (unknown origin) by discoverX kinome scan assay	ic50	0.0008	uM
7-[6-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]-2-pyridinyl]-N-[4-(4-methylpiperazin-1-yl)phenyl]-6-propylpyrrolo[2,3-d]pyrimidin-2-amine	1921871: Inhibition of Wee1 (unknown origin) incubated for 60 mins by LanthaScreen Eu-Kinase binding assay	ic50	0.0008	uM
2-[6-[6-cyclopropyl-5-fluoro-2-[4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino]pyrrolo[2,3-d]pyrimidin-7-yl]-2-pyridinyl]propan-2-ol	1921871: Inhibition of Wee1 (unknown origin) incubated for 60 mins by LanthaScreen Eu-Kinase binding assay	ic50	0.0009	uM
2-[6-[2-[4-(4-methylpiperazin-1-yl)anilino]-6-propylpyrrolo[2,3-d]pyrimidin-7-yl]-2-pyridinyl]propan-2-ol	1921871: Inhibition of Wee1 (unknown origin) incubated for 60 mins by LanthaScreen Eu-Kinase binding assay	ic50	0.0009	uM
6-cyclopropyl-7-[6-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]-2-pyridinyl]-N-[4-(4-methylpiperazin-1-yl)phenyl]pyrrolo[2,3-d]pyrimidin-2-amine	1921871: Inhibition of Wee1 (unknown origin) incubated for 60 mins by LanthaScreen Eu-Kinase binding assay	ic50	0.0009	uM
7-[6-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]-2-pyridinyl]-N-[4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-6-propylpyrrolo[2,3-d]pyrimidin-2-amine	1921871: Inhibition of Wee1 (unknown origin) incubated for 60 mins by LanthaScreen Eu-Kinase binding assay	ic50	0.0009	uM
6-(4-piperazin-1-ylanilino)-2-prop-2-enyl-1-(6-pyrimidin-2-yl-2-pyridinyl)pyrazolo[3,4-d]pyrimidin-3-one	2077776: Inhibition of human Wee1 (215 to 647 residues) using polyornithine/tyrosine (4:1) as substrate incubated for 5 mins in presence of ATP by micro beta plate reader analysis	ic50	0.0009	uM
7-[6-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]-2-pyridinyl]-N-[4-(4-methylpiperazin-1-yl)phenyl]-6-propan-2-ylpyrrolo[2,3-d]pyrimidin-2-amine	1921871: Inhibition of Wee1 (unknown origin) incubated for 60 mins by LanthaScreen Eu-Kinase binding assay	ic50	0.0010	uM
2-[6-[6-cyclopropyl-2-[4-(9-methyl-3,9-diazaspiro[5.5]undecan-3-yl)anilino]pyrrolo[2,3-d]pyrimidin-7-yl]-2-pyridinyl]propan-2-ol	1872284: Displacement of tracer 178 from N-terminal GST-fused human WEE1 (215 to 646 residues) expressed in baculovirus expression system preincubated for 5 mins followed by tracer addition measured after 60 mins by Lantha Screen EU assay	ic50	0.0010	uM
7-(2,6-dichlorophenyl)-12-[(2,4,4-trimethyl-1,3-dihydroisoquinolin-7-yl)amino]-2,5,7,11,13-pentazatricyclo[7.4.0.02,6]trideca-1(13),3,5,9,11-pentaen-8-one	1177251: Inhibition of GST-tagged human Wee1	ki	0.0010	uM
7-(2-chloro-6-fluorophenyl)-12-[(2,4,4-trimethyl-1,3-dihydroisoquinolin-7-yl)amino]-2,5,7,11,13-pentazatricyclo[7.4.0.02,6]trideca-1(13),3,5,9,11-pentaen-8-one	1177251: Inhibition of GST-tagged human Wee1	ki	0.0010	uM
7-(2,6-dichlorophenyl)-12-[(2-methylspiro[1,3-dihydroisoquinoline-4,1’-cyclopropane]-7-yl)amino]-2,5,7,11,13-pentazatricyclo[7.4.0.02,6]trideca-1(13),3,5,9,11-pentaen-8-one	1177251: Inhibition of GST-tagged human Wee1	ki	0.0010	uM
7-(2,6-dichlorophenyl)-12-[4-(4-methylpiperazin-1-yl)anilino]-2,5,7,11,13-pentazatricyclo[7.4.0.02,6]trideca-1(13),3,5,9,11-pentaen-8-one	1177251: Inhibition of GST-tagged human Wee1	ki	0.0010	uM
7-(2-chloro-6-fluorophenyl)-12-[(2-methylspiro[1,3-dihydroisoquinoline-4,1’-cyclopropane]-7-yl)amino]-2,5,7,11,13-pentazatricyclo[7.4.0.02,6]trideca-1(13),3,5,9,11-pentaen-8-one	1177251: Inhibition of GST-tagged human Wee1	ki	0.0010	uM
7-(2-chlorophenyl)-12-[(2,4,4-trimethyl-1,3-dihydroisoquinolin-7-yl)amino]-2,5,7,11,13-pentazatricyclo[7.4.0.02,6]trideca-1(13),3,5,9,11-pentaen-8-one	1177251: Inhibition of GST-tagged human Wee1	ki	0.0010	uM
8-cyclopropyl-6-(2,6-dichlorophenyl)-2-[4-(4-methylpiperazin-1-yl)anilino]pyrido[2,3-d]pyrimidin-5-one	1589875: Binding affinity to wild type N-terminal GST-tagged human WEE1 catalytic domain (215 to 646 residues) expressed in baculovirus expression system measured after 1 hr by TR-FRET assay	ki	0.0010	uM
7-(2-chlorophenyl)-12-[(2-methylspiro[1,3-dihydroisoquinoline-4,1’-cyclopropane]-7-yl)amino]-2,5,7,11,13-pentazatricyclo[7.4.0.02,6]trideca-1(13),3,5,9,11-pentaen-8-one	1177251: Inhibition of GST-tagged human Wee1	ki	0.0012	uM
2-[6-[6-cyclopropyl-2-[4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino]pyrrolo[2,3-d]pyrimidin-7-yl]-2-pyridinyl]propan-2-ol	1921871: Inhibition of Wee1 (unknown origin) incubated for 60 mins by LanthaScreen Eu-Kinase binding assay	ic50	0.0013	uM
6-(2,6-dichlorophenyl)-2-[4-(4-methylpiperazin-1-yl)anilino]-8-(oxetan-3-yl)pyrido[2,3-d]pyrimidin-5-one	1589875: Binding affinity to wild type N-terminal GST-tagged human WEE1 catalytic domain (215 to 646 residues) expressed in baculovirus expression system measured after 1 hr by TR-FRET assay	ki	0.0013	uM
2-prop-2-enyl-1-(6-pyrimidin-2-yl-2-pyridinyl)-6-(1,2,3,4-tetrahydroisoquinolin-7-ylamino)pyrazolo[3,4-d]pyrimidin-3-one	2077776: Inhibition of human Wee1 (215 to 647 residues) using polyornithine/tyrosine (4:1) as substrate incubated for 5 mins in presence of ATP by micro beta plate reader analysis	ic50	0.0014	uM
5,9,11-trihydroxy-2-methylnaphtho[3,2-h]chromene-4,7,12-trione	610761: Binding affinity to weel kinase	kd	0.0014	uM
6-[4-(4-ethylpiperazin-1-yl)anilino]-2-prop-2-enyl-1-(6-pyrazin-2-yl-2-pyridinyl)pyrazolo[3,4-d]pyrimidin-3-one	2077776: Inhibition of human Wee1 (215 to 647 residues) using polyornithine/tyrosine (4:1) as substrate incubated for 5 mins in presence of ATP by micro beta plate reader analysis	ic50	0.0016	uM
7-(2-chlorophenyl)-12-[(2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)amino]-2,5,7,11,13-pentazatricyclo[7.4.0.02,6]trideca-1(13),3,5,9,11-pentaen-8-one	1177251: Inhibition of GST-tagged human Wee1	ki	0.0016	uM
6-[4-[2-(dimethylamino)ethyl]anilino]-1-[6-(2-hydroxypropan-2-yl)-2-pyridinyl]-2-prop-2-enylpyrazolo[3,4-d]pyrimidin-3-one	1927501: Inhibition of recombinant Wee1 (unknown origin) by TR-FRET assay	ic50	0.0017	uM
6-[4-[(3S,5R)-3,5-dimethylpiperazin-1-yl]anilino]-2-prop-2-enyl-1-(6-pyrazin-2-yl-2-pyridinyl)pyrazolo[3,4-d]pyrimidin-3-one	2077776: Inhibition of human Wee1 (215 to 647 residues) using polyornithine/tyrosine (4:1) as substrate incubated for 5 mins in presence of ATP by micro beta plate reader analysis	ic50	0.0017	uM
6-[4-[(3aS,6aR)-2-methyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]anilino]-1-[5-(2-hydroxypropan-2-yl)-2-pyridinyl]-2-prop-2-enylpyrazolo[3,4-d]pyrimidin-3-one	1872270: Inhibition of N-terminal GST-tagged wild-type WEE1 (215 to 646 residues) (unknown origin) expressed in Sf21 insect cells incubated for 60 mins in presence of ATP by ELISA	ic50	0.0018	uM
1-[6-(5-fluoro-2-pyridinyl)-2-pyridinyl]-6-[4-(4-methylpiperazin-1-yl)anilino]-2-prop-2-enylpyrazolo[3,4-d]pyrimidin-3-one	2077776: Inhibition of human Wee1 (215 to 647 residues) using polyornithine/tyrosine (4:1) as substrate incubated for 5 mins in presence of ATP by micro beta plate reader analysis	ic50	0.0018	uM
6-[4-(1-methylpiperidin-4-yl)anilino]-2-prop-2-enyl-1-(6-pyridazin-3-yl-2-pyridinyl)pyrazolo[3,4-d]pyrimidin-3-one	2077776: Inhibition of human Wee1 (215 to 647 residues) using polyornithine/tyrosine (4:1) as substrate incubated for 5 mins in presence of ATP by micro beta plate reader analysis	ic50	0.0018	uM
7-[6-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]-2-pyridinyl]-6-(methoxymethyl)-N-[4-(4-methylpiperazin-1-yl)phenyl]pyrrolo[2,3-d]pyrimidin-2-amine	1921871: Inhibition of Wee1 (unknown origin) incubated for 60 mins by LanthaScreen Eu-Kinase binding assay	ic50	0.0020	uM
6-[4-(4-methylpiperazin-1-yl)anilino]-2-prop-2-enyl-1-(6-pyridazin-3-yl-2-pyridinyl)pyrazolo[3,4-d]pyrimidin-3-one	2077776: Inhibition of human Wee1 (215 to 647 residues) using polyornithine/tyrosine (4:1) as substrate incubated for 5 mins in presence of ATP by micro beta plate reader analysis	ic50	0.0020	uM
6-[4-(3-methyl-3,8-diazabicyclo[3.2.1]octan-8-yl)anilino]-2-prop-2-enyl-1-(6-pyrazin-2-yl-2-pyridinyl)pyrazolo[3,4-d]pyrimidin-3-one	2077776: Inhibition of human Wee1 (215 to 647 residues) using polyornithine/tyrosine (4:1) as substrate incubated for 5 mins in presence of ATP by micro beta plate reader analysis	ic50	0.0020	uM

CTD chemical–gene interactions

97 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, affects expression, increases abundance	4
methylmercuric chloride	increases expression, affects cotreatment	3
bisphenol A	decreases expression, decreases methylation	3
Valproic Acid	affects expression, increases expression, increases methylation	3
lasiocarpine	affects cotreatment, affects expression, decreases expression, increases metabolic processing	2
sodium arsenite	decreases expression	2
(+)-JQ1 compound	decreases expression, increases response to substance	2
Arsenic Trioxide	affects expression, decreases phosphorylation, increases expression, increases reaction	2
Cisplatin	affects cotreatment, decreases expression, decreases response to substance, increases expression	2
Quercetin	decreases expression, increases expression	2
Tretinoin	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	affects expression, decreases expression	2
Aflatoxin B1	increases expression, increases methylation	2
Cadmium Chloride	decreases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
RGFP966	decreases expression, increases reaction	1
FR900359	decreases phosphorylation	1
napabucasin	decreases expression	1
mivebresib	decreases expression	1
LCS1269	affects phosphorylation	1
INCB057643	decreases phosphorylation, affects cotreatment	1
triphenyl phosphate	affects expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
morin	increases expression	1
trichostatin A	affects expression	1
riddelliine	decreases expression, increases metabolic processing	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
dioscin	increases expression	1
ochratoxin A	decreases expression	1

ChEMBL screening assays

385 unique, capped per target: 374 binding, 7 functional, 2 admet, 1 unclassified, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4622371	Binding	Protac activity at CRBN/WEE1 in human MOLT4 cells assessed as induction of degradation of WEE1 at 1 uM incubated for 6 hrs by immunoblot analysis relative to control	Chemically Induced Degradation of WEE1 Kinase for Difficult to Treat Diseases. — ACS Med Chem Lett
CHEMBL5332331	Functional	In vivo PROTAC activity at CRBN/Wee1 in human MV4-11 cells xenografted in Nu/Nu mouse assessed as residual Wee1 level at 10 mg/kg,iv measured after 3 hrs by Western blot method (Rvb = 89 to 111%)	Design, synthesis, and biological evaluation of Wee1 kinase degraders. — Eur J Med Chem
CHEMBL1738389	Unclassified	PUBCHEM_BIOASSAY: Late stage results from the probe development effort to identify inhibitors of Wee1 degradation. (Class of assay: screening) [Related pubchem assays (depositor defined):AID1321, AID1410, AID1412, AID1413, AID1414, AID1807,	PubChem BioAssay data set

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.