MKNK2

Summary

MKNK2 (MAPK interacting serine/threonine kinase 2, HGNC:7111) is a protein-coding gene on chromosome 19p13.3, encoding MAP kinase-interacting serine/threonine-protein kinase 2 (Q9HBH9). Serine/threonine-protein kinase that phosphorylates SFPQ/PSF, HNRNPA1 and EIF4E.

This gene encodes a member of the calcium/calmodulin-dependent protein kinases (CAMK) Ser/Thr protein kinase family, which belongs to the protein kinase superfamily. This protein contains conserved DLG (asp-leu-gly) and ENIL (glu-asn-ile-leu) motifs, and an N-terminal polybasic region which binds importin A and the translation factor scaffold protein eukaryotic initiation factor 4G (eIF4G). This protein is one of the downstream kinases activated by mitogen-activated protein (MAP) kinases. It phosphorylates the eukaryotic initiation factor 4E (eIF4E), thus playing important roles in the initiation of mRNA translation, oncogenic transformation and malignant cell proliferation. In addition to eIF4E, this protein also interacts with von Hippel-Lindau tumor suppressor (VHL), ring-box 1 (Rbx1) and Cullin2 (Cul2), which are all components of the CBC(VHL) ubiquitin ligase E3 complex. Multiple alternatively spliced transcript variants have been found, but the full-length nature and biological activity of only two variants are determined. These two variants encode distinct isoforms which differ in activity and regulation, and in subcellular localization.

Source: NCBI Gene 2872 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 102 total
• Druggable target: yes — 41 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_199054

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7111
Approved symbol	MKNK2
Name	MAPK interacting serine/threonine kinase 2
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	MNK2
Ensembl gene	ENSG00000099875
Ensembl biotype	protein_coding
OMIM	605069
Entrez	2872

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 9 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000250896, ENST00000309340, ENST00000585667, ENST00000586620, ENST00000586828, ENST00000587416, ENST00000588014, ENST00000589441, ENST00000589509, ENST00000589534, ENST00000591142, ENST00000591588, ENST00000907124, ENST00000907125, ENST00000907126, ENST00000918502

RefSeq mRNA: 2 — MANE Select: NM_199054 NM_017572, NM_199054

CCDS: CCDS12079, CCDS12080

Canonical transcript exons

ENST00000250896 — 14 exons

Exon	Start	End
ENSE00001376577	2051096	2051244
ENSE00001491579	2050801	2050947
ENSE00002754811	2037471	2039856
ENSE00003519985	2042766	2042870
ENSE00003530858	2043503	2043582
ENSE00003535239	2046367	2046468
ENSE00003551048	2043124	2043197
ENSE00003577878	2041840	2042034
ENSE00003595526	2040134	2040177
ENSE00003609171	2041040	2041204
ENSE00003610244	2046604	2046691
ENSE00003615248	2042607	2042662
ENSE00003622999	2046186	2046283
ENSE00003659191	2042427	2042522

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 99.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 128.9913 / max 5190.5421, expressed in 1828 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178116	122.7246	1826
178104	1.6474	831
178105	1.1447	479
178114	0.5923	272
178110	0.5297	278
178111	0.4668	203
178112	0.4215	204
178106	0.3536	145
178107	0.3285	151
178101	0.2827	112

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
superior surface of tongue	UBERON:0007371	99.69	gold quality
parotid gland	UBERON:0001831	99.68	gold quality
body of tongue	UBERON:0011876	99.68	gold quality
tongue	UBERON:0001723	99.65	gold quality
pharyngeal mucosa	UBERON:0000355	99.62	gold quality
amniotic fluid	UBERON:0000173	99.61	gold quality
buccal mucosa cell	CL:0002336	99.56	gold quality
gastrocnemius	UBERON:0001388	99.56	gold quality
esophagus squamous epithelium	UBERON:0006920	99.48	gold quality
cervix squamous epithelium	UBERON:0006922	99.48	gold quality
upper leg skin	UBERON:0004262	99.47	gold quality
tibialis anterior	UBERON:0001385	99.45	gold quality
epithelium of esophagus	UBERON:0001976	99.45	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.44	gold quality
lower esophagus mucosa	UBERON:0035834	99.44	gold quality
penis	UBERON:0000989	99.43	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.41	gold quality
squamous epithelium	UBERON:0006914	99.41	gold quality
vastus lateralis	UBERON:0001379	99.40	gold quality
gingival epithelium	UBERON:0001949	99.37	gold quality
quadriceps femoris	UBERON:0001377	99.36	gold quality
pylorus	UBERON:0001166	99.34	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.34	gold quality
gingiva	UBERON:0001828	99.33	gold quality
skeletal muscle tissue	UBERON:0001134	99.31	gold quality
mammalian vulva	UBERON:0000997	99.30	gold quality
biceps brachii	UBERON:0001507	99.30	gold quality
trachea	UBERON:0003126	99.28	gold quality
lower lobe of lung	UBERON:0008949	99.27	gold quality
cardia of stomach	UBERON:0001162	99.22	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	16.17
E-MTAB-9067	yes	12.34
E-MTAB-6379	no	105.39

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR2

miRNA regulators (miRDB)

163 targeting MKNK2, 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-513A-5P	100.00	69.77	2465
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872

Literature-anchored findings (GeneRIF, showing 20)

• The N and C termini of the splice variants of the human mitogen-activated protein kinase-interacting kinase Mnk2 determine activity and localization (PMID:12897141)
• Mnk2 can interact with CBC(VHL) complex, and is probably one of the new substrates of the CBC(VHL) complex. (PMID:16856496)
• siRNA-mediated Mnk1/2 knockdown results in partial reversal of the suppressive effects of IFNgamma on human CD34+-derived myeloid (CFU-GM) and erythroid (BFU-E) progenitors. (PMID:21149447)
• MNK2-dependent phosphorylation of eIF4E represents a novel drug resistance, pro-survival pathway in pancreatic ductal carcinoma. (PMID:22797067)
• These findings provide evidence for key and essential roles of the Mnk kinase pathway in the generation of the antineoplastic effects of type I IFNs in Jak2V617F-dependent myeloproliferative neoplasms. (PMID:23814052)
• eIF4E phosphorylation is enhanced by Rapamycin, which activates Mnk2a (PMID:23831578)
• Provide evidence for the existence of a Mnk2/eIF4E-controlled feedback loop in medulloblastoma cells that accounts for resistance to mTORC1 inhibitors. (PMID:25193863)
• MNK1 and MNK2 inhibition ablates eIF4E1 phosphorylation and concurrently enhances eIF4E3 expression in diffuse large B-cell lymphoma. (PMID:25403230)
• Data suggest that a combined pharmacologic inhibition of mTORC1 and Mnk1/2 kinases offers a therapeutic opportunity in blast crisis-chronic myeloid leukemia (BC-CML). (PMID:25527453)
• Data show that interferon-gamma regulated the metabolism and mRNA translation of macrophages by targeting the kinases mTORC1 and MNK1/2, both of which converge on the selective regulator of translation initiation eukaryotic initiation factor-4E (eIF4E). (PMID:26147685)
• Data suggest MNK1/MNK2 stimulate mRNA translation but only of mRNA containing both 5-prime-terminal cap and hairpin duplex; this stimulation involves up-regulation of phosphorylation/mRNA un-winding activity of eIF4E (via decreased binding to eIF4G). (PMID:26668315)
• Data show that galeterone (gal) and VNPT55 inhibit migration and invasion of prostate cancer cells, possibly by down-regulating protein expression via antagonizing the Mnk1/2-eIF4E axis. (PMID:27618366)
• We conclude that MNK2 overexpression in NSCLC is associated with proliferation, migration, invasion, and lower survival rates in patients via the phosphorylated eIF4E-mediated signaling pathway. (PMID:28878291)
• Induction of Mnk2a by splice switching oligonucleotides in glioblastoma cells activated the p38-MAPK pathway, inhibited the oncogenic properties of the cells, re-sensitized the cells to chemotherapy and inhibited glioblastoma development in vivo (PMID:30329087)
• Reciprocal signaling between mTORC1 and MNK2 controls cell growth and oncogenesis. (PMID:32170339)
• MNK1 and MNK2 enforce expression of E2F1, FOXM1, and WEE1 to drive soft tissue sarcoma. (PMID:33564073)
• SRPK1/2 and PP1alpha exert opposite functions by modulating SRSF1-guided MKNK2 alternative splicing in colon adenocarcinoma. (PMID:33602301)
• MKNK2 enhances chemoresistance of ovarian cancer by suppressing autophagy via miR-125b. (PMID:33836345)
• MNK1 and MNK2 Expression in the Human Dorsal Root and Trigeminal Ganglion. (PMID:36764601)
• RBM25 depletion suppresses the growth of colon cancer cells through regulating alternative splicing of MNK2. (PMID:39110401)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	mknk2a	ENSDARG00000011373
danio_rerio	mknk2b	ENSDARG00000015164
mus_musculus	Mknk2	ENSMUSG00000020190
rattus_norvegicus	Mknk2	ENSRNOG00000029028
drosophila_melanogaster	Lk6	FBGN0017581
caenorhabditis_elegans		WBGENE00011304

Paralogs (6): DCX (ENSG00000077279), MKNK1 (ENSG00000079277), MAPKAPK5 (ENSG00000089022), MAPKAPK3 (ENSG00000114738), CAMK4 (ENSG00000152495), MAPKAPK2 (ENSG00000162889)

Protein

Protein identifiers

MAP kinase-interacting serine/threonine-protein kinase 2 — Q9HBH9 (reviewed: Q9HBH9)

Alternative names: MAP kinase signal-integrating kinase 2

All UniProt accessions (6): Q9HBH9, K7EIN7, K7EJ98, K7EK27, K7EMP5, Q9NV89

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase that phosphorylates SFPQ/PSF, HNRNPA1 and EIF4E. May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap. Required for mediating PP2A-inhibition-induced EIF4E phosphorylation. Triggers EIF4E shuttling from cytoplasm to nucleus. Isoform 1 displays a high basal kinase activity, but isoform 2 exhibits a very low kinase activity. Acts as a mediator of the suppressive effects of IFNgamma on hematopoiesis. Negative regulator for signals that control generation of arsenic trioxide As(2)O(3)-dependent apoptosis and anti-leukemic responses. Involved in anti-apoptotic signaling in response to serum withdrawal.

Subunit / interactions. Monomer. Interacts with the C-terminal regions of EIF4G1 and EIF4G2; this interaction is promoted when MAPK pathways are repressed but repressed upon ERK proteins activation. Also binds to dephosphorylated MAPK3/ERK1 and MAPK1/ERK2. Isoform 1 interaction with phosphorylated MAPK3/ERK1 and MAPK1/ERK2 protects it from dephosphorylation and inactivation. Isoform 2 interacts with ESR2 and EIF4E in the nucleus.

Subcellular location. Nucleus. PML body Cytoplasm.

Tissue specificity. Ubiquitously expressed in all tissues examined. Isoform 2 is expressed at higher levels in the ovary than is isoform 1.

Post-translational modifications. Dual phosphorylation of Thr-244 and Thr-249 activates the kinase. Phosphorylation of Thr-379 activates the kinase. Phosphorylated upon arsenic trioxide As(2)O(3) treatment. Phosphorylated by MAPK1/ERK2, MAPK11 and MAPK14. Dephosphorylated by PP2A.

Activity regulation. Inhibited by CGP57380 and staurosporine. Activated by phosphorylation in a negative-feedback regulatory manner in response to chemotherapy (e.g. cytarabine) and thus impairs the generation of antileukemic responses.

Cofactor. Binds 1 zinc ion per subunit.

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

Isoforms (5)

UniProt ID	Names	Canonical?
Q9HBH9-1	1, 2a	yes
Q9HBH9-2	2, 2b
Q9HBH9-3	3
Q9HBH9-4	4
Q9HBH9-5	5

RefSeq proteins (2): NP_060042, NP_951009* (*=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
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR050205	CDPK_Ser/Thr_kinases	Family

Pfam: PF00069

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (58 total): helix 13, strand 12, binding site 7, modified residue 7, mutagenesis site 4, sequence variant 3, turn 3, splice variant 2, short sequence motif 2, chain 1, domain 1, region of interest 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
2AC3	X-RAY DIFFRACTION	2.1
8P9B	X-RAY DIFFRACTION	2.59
8XFM	X-RAY DIFFRACTION	2.6
2HW7	X-RAY DIFFRACTION	2.71
6CJ5	X-RAY DIFFRACTION	2.8
6CK3	X-RAY DIFFRACTION	2.9
6JLR	X-RAY DIFFRACTION	2.9
6CKI	X-RAY DIFFRACTION	2.95
6CJY	X-RAY DIFFRACTION	3.05
9HRC	X-RAY DIFFRACTION	3.16
2AC5	X-RAY DIFFRACTION	3.2
6CK6	X-RAY DIFFRACTION	3.32
6CJE	X-RAY DIFFRACTION	3.36
6CJW	X-RAY DIFFRACTION	3.38
6CJH	X-RAY DIFFRACTION	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HBH9-F1	71.74	0.40

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): 205 (proton acceptor)

Ligand- & substrate-binding residues (7): 299; 311; 314; 90–98; 113; 160–162; 209

Post-translational modifications (7): 74, 244, 249, 379, 437, 440, 452

Mutagenesis-validated functional residues (4):

Position	Phenotype
228	reduced phosphorylation.
244	loss of kinase activity; when associated with t-249.
249	loss of kinase activity; when associated with t-244.
379	constitutively active.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 324 (showing top): RNGTGGGC_UNKNOWN, CCAWYNNGAAR_UNKNOWN, KEGG_MAPK_SIGNALING_PATHWAY, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_DN, CTATGCA_MIR153, GGGTGGRR_PAX4_03, MODULE_503, GOBP_TRANSLATION, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A5, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GERY_CEBP_TARGETS, RICKMAN_METASTASIS_DN, UEDA_PERIFERAL_CLOCK

GO Biological Process (8): regulation of translation (GO:0006417), protein phosphorylation (GO:0006468), cell surface receptor signaling pathway (GO:0007166), hemopoiesis (GO:0030097), intracellular signal transduction (GO:0035556), cellular response to arsenic-containing substance (GO:0071243), extrinsic apoptotic signaling pathway in absence of ligand (GO:0097192), apoptotic process (GO:0006915)

GO Molecular Function (12): protein serine/threonine kinase activity (GO:0004674), calcium/calmodulin-dependent protein kinase activity (GO:0004683), calmodulin binding (GO:0005516), ATP binding (GO:0005524), calcium-dependent protein serine/threonine kinase activity (GO:0009931), metal ion binding (GO:0046872), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nuclear body (GO:0016604), PML body (GO:0016605)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	2
intracellular anatomical structure	2
protein kinase activity	2
protein serine/threonine kinase activity	2
cellular anatomical structure	2
translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
phosphorylation	1
protein modification process	1
cell development	1
response to arsenic-containing substance	1
cellular response to chemical stimulus	1
signal transduction in absence of ligand	1
extrinsic apoptotic signaling pathway	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
protein binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nucleoplasm	1
intracellular membraneless organelle	1
nuclear body	1

Protein interactions and networks

STRING

1098 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MKNK2	ATP7A	Q04656	796
MKNK2	EIF4G1	Q04637	786
MKNK2	EIF4E	P06730	783
MKNK2	EIF4G2	P78344	619
MKNK2	SRSF1	Q07955	549
MKNK2	IPO7	O95373	548
MKNK2	NEK4	P51957	535
MKNK2	MAP2K1	Q02750	518
MKNK2	UBTF	P17480	504
MKNK2	MAPKAP1	Q9BPZ7	459
MKNK2	EIF4EBP2	Q13542	456
MKNK2	CDK4	P11802	455
MKNK2	MAP2K2	P36507	447
MKNK2	MST1R	Q04912	447
MKNK2	SRPK1	Q96SB4	436

IntAct

20 interactions, top by confidence:

A	B	Type	Score
MAPK14	OBSL1	psi-mi:“MI:0914”(association)	0.790
MKNK2	MAPK14	psi-mi:“MI:2364”(proximity)	0.790
SRPK1	MKNK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
LRRK2	MKNK2	psi-mi:“MI:0407”(direct interaction)	0.440
MAPK8	MKNK2	psi-mi:“MI:0915”(physical association)	0.370
MKNK2	WWP2	psi-mi:“MI:0914”(association)	0.350
MKNK2	WDR46	psi-mi:“MI:0914”(association)	0.350
MAPK14	PRKY	psi-mi:“MI:0914”(association)	0.350
MAPK3	HMMR	psi-mi:“MI:0914”(association)	0.350
MKNK1	SEC16A	psi-mi:“MI:0914”(association)	0.350
MKNK2	MAPK3	psi-mi:“MI:0914”(association)	0.350
CUL4B	GGTLC3	psi-mi:“MI:0914”(association)	0.350
GAPDH	ERLIN2	psi-mi:“MI:0914”(association)	0.350
MAPK1	SPAG9	psi-mi:“MI:0914”(association)	0.350
MKNK2	syd	psi-mi:“MI:0915”(physical association)	0.000
MKNK2	MAPK14	psi-mi:“MI:0915”(physical association)	0.000
MKNK2	RPL7A	psi-mi:“MI:0915”(physical association)	0.000
MKNK2	MKNK2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (67): MKNK2 (Affinity Capture-MS), CSTF2 (Affinity Capture-MS), MIF (Affinity Capture-MS), RBM4 (Affinity Capture-MS), VCL (Affinity Capture-MS), BAG6 (Affinity Capture-MS), SYMPK (Affinity Capture-MS), KHSRP (Affinity Capture-MS), NOLC1 (Affinity Capture-MS), WDR46 (Affinity Capture-MS), USP15 (Affinity Capture-MS), TRAP1 (Affinity Capture-MS), CELF1 (Affinity Capture-MS), NUDT21 (Affinity Capture-MS), WWP2 (Affinity Capture-MS)

ESM2 similar proteins: A0AAR7, A1A699, A4IGM9, D0N4E2, O08605, O80673, P15735, P31325, P53681, Q10KY3, Q13555, Q21734, Q2KJ16, Q2QQR2, Q2QVG8, Q43531, Q4G050, Q58D94, Q5NTH4, Q5U2N4, Q66JF3, Q6AVM3, Q6F3A6, Q6GPL3, Q6H5L4, Q6I5I8, Q6RET7, Q76L34, Q7XJR9, Q7XSQ5, Q852N6, Q8GVC7, Q8LPZ7, Q8S9F2, Q96GD4, Q96QS6, Q9BUB5, Q9DB30, Q9FIM9, Q9FKW4

Diamond homologs: A0A509AFG4, A0A509AQE6, A0A5K1K8H0, A2ZVI7, D2I3C6, O08605, O15075, O15865, O54992, O75582, O75676, O77708, P08413, P10665, P11275, P11798, P11801, P15791, P18652, P18653, P18654, P25323, P28582, P28652, P49137, P49138, P49139, P51812, P53683, P62345, Q06850, Q0V7M1, Q13554, Q13557, Q15349, Q15418, Q16644, Q18846, Q2HJF7, Q38868

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
MKNK2	up-regulates	EIF4E	phosphorylation
Tomivosertib	“down-regulates activity”	MKNK2	“chemical inhibition”
Gbeta	up-regulates	MKNK2	phosphorylation
ERK1/2	up-regulates	MKNK2	phosphorylation
MTOR	“down-regulates activity”	MKNK2	phosphorylation
MAPK1	up-regulates	MKNK2	phosphorylation
MAPK14	up-regulates	MKNK2	phosphorylation
MAPK3	up-regulates	MKNK2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 20 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
Infectious disease	5	7.3×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
MAPK cascade	5	42.6×	9e-06
protein phosphorylation	6	22.6×	1e-05
intracellular signal transduction	6	12.7×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	61
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1392 predictions. Top by Δscore:

Variant	Effect	Δscore
19:2039852:TGTTC:T	acceptor_gain	1.0000
19:2039857:C:CC	acceptor_gain	1.0000
19:2040178:C:CC	acceptor_gain	1.0000
19:2041036:TCA:T	donor_loss	1.0000
19:2041037:CA:C	donor_loss	1.0000
19:2041038:A:AC	donor_gain	1.0000
19:2041038:AC:A	donor_gain	1.0000
19:2041038:ACC:A	donor_gain	1.0000
19:2041038:ACCC:A	donor_gain	1.0000
19:2041038:ACCCC:A	donor_gain	1.0000
19:2041039:C:CC	donor_gain	1.0000
19:2041039:CC:C	donor_gain	1.0000
19:2041039:CCC:C	donor_gain	1.0000
19:2041039:CCCC:C	donor_gain	1.0000
19:2041039:CCCCC:C	donor_gain	1.0000
19:2041080:AG:A	donor_gain	1.0000
19:2041081:G:C	donor_gain	1.0000
19:2041200:ATGTT:A	acceptor_gain	1.0000
19:2041201:TGTT:T	acceptor_gain	1.0000
19:2041202:GTT:G	acceptor_gain	1.0000
19:2041203:TT:T	acceptor_gain	1.0000
19:2041204:TCTGG:T	acceptor_loss	1.0000
19:2041205:C:CA	acceptor_loss	1.0000
19:2041205:C:CC	acceptor_gain	1.0000
19:2041212:C:CT	acceptor_gain	1.0000
19:2041213:A:AC	acceptor_gain	1.0000
19:2041213:A:C	acceptor_gain	1.0000
19:2041834:CCGCA:C	donor_loss	1.0000
19:2041835:CGCA:C	donor_loss	1.0000
19:2041836:GCAC:G	donor_loss	1.0000

AlphaMissense

3076 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:2041051:A:G	W367R	1.000
19:2041051:A:T	W367R	1.000
19:2041082:C:A	R356S	1.000
19:2041082:C:G	R356S	1.000
19:2041083:C:A	R356M	1.000
19:2041083:C:G	R356T	1.000
19:2041107:A:G	L348P	1.000
19:2041119:A:G	L344P	1.000
19:2041150:A:G	W334R	1.000
19:2041150:A:T	W334R	1.000
19:2041900:G:C	F295L	1.000
19:2041900:G:T	F295L	1.000
19:2041902:A:G	F295L	1.000
19:2041904:G:T	P294H	1.000
19:2041940:C:A	G282V	1.000
19:2041940:C:T	G282D	1.000
19:2041941:C:G	G282R	1.000
19:2041945:G:C	S280R	1.000
19:2041945:G:T	S280R	1.000
19:2041947:T:G	S280R	1.000
19:2041948:C:A	W279C	1.000
19:2041948:C:G	W279C	1.000
19:2041950:A:G	W279R	1.000
19:2041950:A:T	W279R	1.000
19:2041955:T:A	D277V	1.000
19:2041955:T:C	D277G	1.000
19:2041955:T:G	D277A	1.000
19:2041956:C:A	D277Y	1.000
19:2041956:C:G	D277H	1.000
19:2041958:C:T	C276Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000105851 (19:2047598 G>C), RS1000392159 (19:2039330 C>T), RS1000395692 (19:2047392 G>A), RS1000900316 (19:2050696 G>A,T), RS1000930833 (19:2050865 C>T), RS1001000954 (19:2046383 G>A), RS1001278469 (19:2047906 C>A,T), RS1001379234 (19:2051082 G>A), RS1001431830 (19:2051204 G>A,C), RS1001455913 (19:2043315 A>C,T), RS1001568830 (19:2039536 C>A,G,T), RS1001652931 (19:2047086 C>T), RS1002085980 (19:2051566 C>A,T), RS1002377089 (19:2050194 G>A), RS1002403106 (19:2047194 C>CCCCCAGGACACAGATGT)

Disease associations

OMIM: gene MIM:605069 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004088_13	Nonsyndromic cleft lip with or without cleft palate	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0003959	cleft lip

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3883293 (PROTEIN FAMILY), CHEMBL4204 (SINGLE PROTEIN), CHEMBL6195561 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

41 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 537,987 (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
CHEMBL1173655	AFATINIB	4	15,144
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL2103743	TOFACITINIB CITRATE	4	1,672
CHEMBL221959	TOFACITINIB	4	10,408
CHEMBL2403108	CERITINIB	4	8,551
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL535	SUNITINIB	4	79,020
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL576982	QUIZARTINIB	4	4,432
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL939	GEFITINIB	4	117,814
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL31965	CANERTINIB	3	8,083
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL603469	LESTAURTINIB	3
CHEMBL4073443	TOMIVOSERTIB	2	473
CHEMBL4211649	TINODASERTIB	2	53
CHEMBL103667	DORAMAPIMOD	2	1,681
CHEMBL1230609	FORETINIB	2
CHEMBL151	LUTEOLIN	2
CHEMBL1721885	SU-014813	2
CHEMBL1738757	REBASTINIB	2
CHEMBL1967878	CENISERTIB	2
CHEMBL1980297	ILORASERTIB	2
CHEMBL215152	DEFOSBARASERTIB	2
CHEMBL230011	TG100-115	2
CHEMBL3545307	MERESTINIB	2
CHEMBL475251	R-406	2

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — MKN subfamily

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

Ligand	Action	Affinity	Parameter
compound 20j [PMID: 38564512]	Inhibition	9.4	pIC50
tomivosertib	Inhibition	9.0	pIC50
tinodasertib	Inhibition	7.07	pIC50
MELK-TI	Inhibition	6.12	pIC50
MNK1 inhibitor	Inhibition	5.8	pIC50

Binding affinities (BindingDB)

843 measured of 1163 human assays (1163 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
5-chloro-7-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]-N-[4-fluoro-2-[(2R)-1,1,1-trifluoropropan-2-yl]oxyphenyl]quinazolin-4-amine	IC50	1 nM	US-9139577: Sulfoximine substituted quinazolines for pharmaceutical compositions
N-[2-(1,3-difluoropropan-2-yloxy)-4-fluorophenyl]-7-[(4-oxo-1,4-oxathian-4-ylidene)amino]-5-(trifluoromethyl)quinazolin-4-amine	IC50	1 nM	US-9139577: Sulfoximine substituted quinazolines for pharmaceutical compositions
5-methyl-N-[2-(oxolan-3-ylmethoxy)-3-pyridinyl]-7-[(1-oxothiolan-1-ylidene)amino]quinazolin-4-amine	IC50	1 nM	US-9139577: Sulfoximine substituted quinazolines for pharmaceutical compositions
N-[4-fluoro-2-[(1R)-1-(3-methyl-1,2-oxazol-5-yl)ethoxy]phenyl]-5-methyl-7-[(1-oxo-1,4-thiazinan-1-ylidene)amino]quinazolin-4-amine	IC50	1 nM	US-9139577: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-2-[2-[[7-[[(3S)-3-amino-1-oxothiolan-1-ylidene]amino]-5-methylquinazolin-4-yl]amino]-5-fluorophenoxy]-N-(2,2,2-trifluoroethyl)propanamide	IC50	1 nM	US-9139577: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-N-(cyanomethyl)-2-[2-[[7-[(3,3-dimethyl-1-oxothietan-1-ylidene)amino]-5-fluoroquinazolin-4-yl]amino]-5-fluorophenoxy]propanamide	IC50	1 nM	US-9139577: Sulfoximine substituted quinazolines for pharmaceutical compositions
methyl 2-[4-[4-fluoro-2-[(2R)-1-oxo-1-(2,2,2-trifluoroethylamino)propan-2-yl]oxyanilino]-5-methylquinazolin-7-yl]imino-2-oxo-2lambda6-thia-6-azaspiro[3.3]heptane-6-carboxylate	IC50	1 nM	US-9139577: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-2-[5-chloro-2-[[7-[(3,3-dimethyl-1-oxothietan-1-ylidene)amino]-5-methylquinazolin-4-yl]amino]phenoxy]-N-[(2S)-1,1,1-trifluoropropan-2-yl]propanamide	IC50	1 nM	US-9139577: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-2-[5-fluoro-2-[[5-methyl-7-[(1-oxothietan-1-ylidene)amino]quinazolin-4-yl]amino]phenoxy]-N-(1,1,1,3,3,3-hexafluoropropan-2-yl)propanamide	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-2-[2-[[7-[(3,3-dimethyl-1-oxothietan-1-ylidene)amino]-5-methylquinazolin-4-yl]amino]-5-fluorophenoxy]-N-(2,2,2-trifluoroethyl)propanamide	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-2-[5-chloro-2-[[5-methyl-7-[(2-oxo-6-oxa-2lambda6-thiaspiro[3.3]heptan-2-ylidene)amino]quinazolin-4-yl]amino]phenoxy]-N-[(2S)-1,1,1-trifluoropropan-2-yl]propanamide	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
2-[2-[[7-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]-5-methylquinazolin-4-yl]amino]-5-fluorophenoxy]acetonitrile	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
7-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]-N-[4-fluoro-2-(oxan-2-ylmethoxy)phenyl]-5-methylquinazolin-4-amine	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
N-[2-[(2R)-1-aminopropan-2-yl]oxy-4-fluorophenyl]-7-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]-5-methylquinazolin-4-amine	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-2-[5-fluoro-2-[[5-fluoro-7-[(1-oxothiolan-1-ylidene)amino]quinazolin-4-yl]amino]phenoxy]-N-(2,2,2-trifluoroethyl)propanamide	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-2-[5-fluoro-2-[[5-methyl-7-[(1-oxothiolan-1-ylidene)amino]quinazolin-4-yl]amino]phenoxy]-N-prop-2-ynylpropanamide	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-N-(2,2-difluoroethyl)-2-[2-[[7-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]-5-methylquinazolin-4-yl]amino]-5-fluorophenoxy]propanamide	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-N-(cyanomethyl)-2-[2-[[7-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]-5-methylquinazolin-4-yl]amino]-5-fluorophenoxy]propanamide	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-2-[5-fluoro-2-[[5-methyl-7-[(1-oxothiolan-1-ylidene)amino]quinazolin-4-yl]amino]phenoxy]-N-propan-2-ylpropanamide	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-N-butan-2-yl-2-[5-fluoro-2-[[5-methyl-7-[(1-oxothiolan-1-ylidene)amino]quinazolin-4-yl]amino]phenoxy]propanamide	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-2-[5-chloro-2-[[5-methyl-7-[(1-oxothietan-1-ylidene)amino]quinazolin-4-yl]amino]phenoxy]-N-[(2S)-1,1,1-trifluoropropan-2-yl]propanamide	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-2-[5-fluoro-2-[[5-methyl-7-[(1-oxothietan-1-ylidene)amino]quinazolin-4-yl]amino]phenoxy]-N-(3,3,3-trifluoropropyl)propanamide	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-2-[2-[[5-chloro-7-[(1-oxothietan-1-ylidene)amino]quinazolin-4-yl]amino]-5-fluorophenoxy]-N-[(2R)-1,1,1-trifluoropropan-2-yl]propanamide	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-2-[2-[[5-chloro-7-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]quinazolin-4-yl]amino]-5-fluorophenoxy]-N-(2,2,2-trifluoroethyl)propanamide	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-2-[5-chloro-2-[[5-fluoro-7-[(1-oxothiolan-1-ylidene)amino]quinazolin-4-yl]amino]phenoxy]-N-[(1S)-1-cyanoethyl]propanamide	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-2-[[6-chloro-3-[[5-methyl-7-[(1-oxothietan-1-ylidene)amino]quinazolin-4-yl]amino]-2-pyridinyl]oxy]-N-[(2S)-1,1,1-trifluoropropan-2-yl]propanamide	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-2-[2-[[5-chloro-7-[(1-oxothietan-1-ylidene)amino]quinazolin-4-yl]amino]-5-fluorophenoxy]-N-[(2S)-1,1,1-trifluoropropan-2-yl]propanamide	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-N-(cyanomethyl)-2-[5-fluoro-2-[[5-fluoro-7-[(1-oxothietan-1-ylidene)amino]quinazolin-4-yl]amino]phenoxy]propanamide	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-N-(cyanomethyl)-2-[5-fluoro-2-[[5-methyl-7-[(1-oxothietan-1-ylidene)amino]quinazolin-4-yl]amino]phenoxy]propanamide	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-2-[5-fluoro-2-[[5-methyl-7-[(1-oxothietan-1-ylidene)amino]quinazolin-4-yl]amino]phenoxy]-N-[(2S)-1,1,1-trifluoropropan-2-yl]propanamide	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-2-[5-chloro-2-[[5-methyl-7-[(1-oxothietan-1-ylidene)amino]quinazolin-4-yl]amino]phenoxy]-N-(2,2-difluoroethyl)propanamide	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-N-[(1R)-1-cyanoethyl]-2-[5-fluoro-2-[[5-fluoro-7-[(1-oxothietan-1-ylidene)amino]quinazolin-4-yl]amino]phenoxy]propanamide	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-2-[5-chloro-2-[[5-methyl-7-[(1-oxothietan-1-ylidene)amino]quinazolin-4-yl]amino]phenoxy]-N-(2,2,2-trifluoroethyl)propanamide	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-2-[[6-chloro-3-[[5-methyl-7-[(1-oxothietan-1-ylidene)amino]quinazolin-4-yl]amino]-2-pyridinyl]oxy]-N-(2,2,2-trifluoroethyl)propanamide	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-2-[5-chloro-2-[[5-methyl-7-[(1-oxothietan-1-ylidene)amino]quinazolin-4-yl]amino]phenoxy]-N-(1,1-difluoropropan-2-yl)propanamide	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-N-(1,3-difluoropropan-2-yl)-2-[5-fluoro-2-[[5-methyl-7-[(1-oxothietan-1-ylidene)amino]quinazolin-4-yl]amino]phenoxy]propanamide	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-N-(1-cyanoethyl)-2-[5-fluoro-2-[[5-methyl-7-[(1-oxothietan-1-ylidene)amino]quinazolin-4-yl]amino]phenoxy]propanamide	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-2-[2-[[5-chloro-7-[(1-oxothietan-1-ylidene)amino]quinazolin-4-yl]amino]-5-fluorophenoxy]-N-[(1S)-1-cyanoethyl]propanamide	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-2-[5-fluoro-2-[[5-methyl-7-[(1-oxothietan-1-ylidene)amino]quinazolin-4-yl]amino]phenoxy]-N-(2,2,2-trifluoroethyl)propanamide	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-2-[[6-chloro-3-[[5-methyl-7-[(1-oxothietan-1-ylidene)amino]quinazolin-4-yl]amino]-2-pyridinyl]oxy]-N-[(1S)-1-cyanoethyl]propanamide	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
(2R)-N-(2,2-difluoroethyl)-2-[5-fluoro-2-[[5-methyl-7-[(1-oxothietan-1-ylidene)amino]quinazolin-4-yl]amino]phenoxy]propanamide	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
N-[(2S)-2-[2-[[7-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]-5-methylquinazolin-4-yl]amino]-5-fluorophenoxy]propyl]methanesulfonamide	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
N-[4-fluoro-2-[(1R)-1-(3-methyl-1,2-oxazol-5-yl)ethoxy]phenyl]-5-methyl-7-[(4-methyl-1-oxo-1,4-thiazinan-1-ylidene)amino]quinazolin-4-amine	IC50	1 nM	US-9708274: Sulfoximine substituted quinazolines for pharmaceutical compositions
(3R,4R)-4-[2-[[5-chloro-7-[(1-oxothietan-1-ylidene)amino]quinazolin-4-yl]amino]-5-fluorophenoxy]oxolan-3-ol	IC50	1 nM	US-10093660: Sulfoximine substituted quinazolines for pharmaceutical compositions
N-[2-[(3R,4S)-4-methoxyoxolan-3-yl]oxy-3-pyridinyl]-5-methyl-7-[(1-oxothiolan-1-ylidene)amino]quinazolin-4-amine	IC50	1 nM	US-10093660: Sulfoximine substituted quinazolines for pharmaceutical compositions
(3S,4S)-4-[[6-chloro-3-[[5-methoxy-7-[(1-oxothietan-1-ylidene)amino]quinazolin-4-yl]amino]-2-pyridinyl]oxy]oxolan-3-ol	IC50	1 nM	US-10093660: Sulfoximine substituted quinazolines for pharmaceutical compositions
N-[2-[[(3aR,6R,6aS)-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-4-fluorophenyl]-6-methoxy-5-methyl-7-[(1-oxothiolan-1-ylidene)amino]quinazolin-4-amine	IC50	1.2 nM	US-10167296: Sulfoximine substituted quinazolines for pharmaceutical compositions
1-[4-[2-[[(3aR,6R,6aS)-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-4-fluoroanilino]-6-methoxy-5-methylquinazolin-7-yl]imino-1-oxothian-4-ol	IC50	1.2 nM	US-10167296: Sulfoximine substituted quinazolines for pharmaceutical compositions
N-[2-[[(3R,3aR,6R,6aR)-3-methoxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-4-fluorophenyl]-5-chloro-6-methoxy-7-[(1-oxothietan-1-ylidene)amino]quinazolin-4-amine	IC50	1.3 nM	US-10167296: Sulfoximine substituted quinazolines for pharmaceutical compositions

ChEMBL bioactivities

2245 potent at pChembl≥5 of 2266 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.08	IC50	0.084	nM	CHEMBL4086747
9.89	IC50	0.13	nM	CHEMBL4094975
9.85	IC50	0.14	nM	CHEMBL4067557
9.51	IC50	0.31	nM	CHEMBL4073743
9.44	IC50	0.36	nM	CHEMBL4086747
9.40	IC50	0.4	nM	CHEMBL5559028
9.30	IC50	0.5	nM	CHEMBL5561551
9.22	EC50	0.6	nM	CHEMBL3800585
9.22	IC50	0.6	nM	CHEMBL5556268
9.21	IC50	0.62	nM	CHEMBL4094975
9.19	IC50	0.64	nM	CHEMBL5561655
9.17	IC50	0.68	nM	CHEMBL4076439
9.15	IC50	0.7	nM	CHEMBL3797873
9.15	IC50	0.7	nM	CHEMBL5560746
9.10	IC50	0.79	nM	CHEMBL4076439
9.10	IC50	0.8	nM	CHEMBL5825302
9.00	IC50	1	nM	CHEMBL3798762
9.00	IC50	1	nM	CHEMBL4111493
9.00	IC50	1	nM	CHEMBL4113944
9.00	IC50	1	nM	CHEMBL4109804
9.00	IC50	1	nM	CHEMBL3969508
9.00	IC50	1	nM	CHEMBL3916533
9.00	IC50	1	nM	CHEMBL4112682
9.00	IC50	1	nM	CHEMBL4112720
9.00	IC50	1	nM	CHEMBL4106829
9.00	IC50	1	nM	CHEMBL4111586
9.00	IC50	1	nM	CHEMBL4110377
9.00	IC50	1	nM	CHEMBL4114582
9.00	IC50	1	nM	CHEMBL4107908
9.00	IC50	1	nM	CHEMBL4111078
9.00	IC50	1	nM	CHEMBL4108347
9.00	IC50	1	nM	CHEMBL4110758
9.00	IC50	1	nM	CHEMBL4108416
9.00	IC50	1	nM	CHEMBL3963888
9.00	IC50	1	nM	CHEMBL3926461
9.00	IC50	1	nM	CHEMBL4114923
9.00	IC50	1	nM	CHEMBL3904562
9.00	IC50	1	nM	CHEMBL4112632
9.00	IC50	1	nM	CHEMBL4107951
9.00	IC50	1	nM	CHEMBL4108049
9.00	IC50	1	nM	CHEMBL4111906
9.00	IC50	1	nM	CHEMBL4110019
9.00	IC50	1	nM	CHEMBL4109353
9.00	IC50	1	nM	CHEMBL4111615
9.00	IC50	1	nM	CHEMBL4115507
9.00	IC50	1	nM	CHEMBL4109890
9.00	IC50	1	nM	CHEMBL4111236
9.00	IC50	1	nM	CHEMBL4106658
9.00	IC50	1	nM	CHEMBL4110073
9.00	IC50	1	nM	CHEMBL4115641

PubChem BioAssay actives

636 with measured affinity, of 2607 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
6-[(6-aminopyrimidin-4-yl)amino]-8-chloro-3,3-dimethyl-2H-imidazo[1,5-a]pyridine-1,5-dione	1479625: Inhibition of full length N-terminal GST-tagged recombinant human MNK2 expressed in baculovirus expression system using Ac-TATKSGSTTKNR-NH2 as substrate preincubated for 5 mins followed by ATP addition measured after 40 mins by ADP-Glo assay	ic50	0.0001	uM
6-[(6-aminopyrimidin-4-yl)amino]-8-chlorospiro[2H-imidazo[1,5-a]pyridine-3,1’-cyclopentane]-1,5-dione	1479625: Inhibition of full length N-terminal GST-tagged recombinant human MNK2 expressed in baculovirus expression system using Ac-TATKSGSTTKNR-NH2 as substrate preincubated for 5 mins followed by ATP addition measured after 40 mins by ADP-Glo assay	ic50	0.0001	uM
6-[(6-amino-5-chloropyrimidin-4-yl)amino]-8-chlorospiro[2H-imidazo[1,5-a]pyridine-3,1’-cyclohexane]-1,5-dione	1479626: Inhibition of MNK1/2 in human HCT116 cells assessed as decrease in eIF4E phosphorylation at Ser209 after 2 hrs by HTRF assay	ic50	0.0001	uM
N-[6-[(8-chloro-1,5-dioxospiro[2H-imidazo[1,5-a]pyridine-3,1’-cyclohexane]-6-yl)amino]pyrimidin-4-yl]cyclopropanecarboxamide	1479626: Inhibition of MNK1/2 in human HCT116 cells assessed as decrease in eIF4E phosphorylation at Ser209 after 2 hrs by HTRF assay	ic50	0.0003	uM
[4-[3-(1-benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]phenyl]-(4-piperidin-1-ylpiperidin-1-yl)methanone	2083031: Inhibition of recombinant MNK2 (unknown origin) using TATKSGSTTKNR as substrate preincubated for 15 mins followed by ATP addition and measured after 1 hr by ADP-glo kinase assay	ic50	0.0004	uM
(4-aminopiperidin-1-yl)-[4-[3-(1-benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]phenyl]methanone	2083031: Inhibition of recombinant MNK2 (unknown origin) using TATKSGSTTKNR as substrate preincubated for 15 mins followed by ATP addition and measured after 1 hr by ADP-glo kinase assay	ic50	0.0005	uM
2-[5-amino-6-[1-methyl-7-[(3S)-3-methylpiperazin-1-yl]benzimidazol-2-yl]pyrazin-2-yl]-N,N-dimethylpyridine-4-carboxamide	1296847: Inhibition of MNK1/2 in human KMS11-luc cells assessed as inhibition of EIF4E phosphorylation at S209 after 3 hrs by quantitative electrochemiluminescence assay	ec50	0.0006	uM
[4-[3-(1-benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]phenyl]-piperazin-1-ylmethanone	2083031: Inhibition of recombinant MNK2 (unknown origin) using TATKSGSTTKNR as substrate preincubated for 15 mins followed by ATP addition and measured after 1 hr by ADP-glo kinase assay	ic50	0.0006	uM
(4-aminopiperidin-1-yl)-[4-[3-(1-benzofuran-2-yl)imidazo[1,2-a]pyridin-6-yl]phenyl]methanone	2083031: Inhibition of recombinant MNK2 (unknown origin) using TATKSGSTTKNR as substrate preincubated for 15 mins followed by ATP addition and measured after 1 hr by ADP-glo kinase assay	ic50	0.0006	uM
6-[(6-aminopyrimidin-4-yl)amino]-8-chlorospiro[2H-imidazo[1,5-a]pyridine-3,1’-cyclohexane]-1,5-dione	1479625: Inhibition of full length N-terminal GST-tagged recombinant human MNK2 expressed in baculovirus expression system using Ac-TATKSGSTTKNR-NH2 as substrate preincubated for 5 mins followed by ATP addition measured after 40 mins by ADP-Glo assay	ic50	0.0007	uM
3-[5-amino-6-[1-methyl-7-[(3S)-3-methylpiperazin-1-yl]benzimidazol-2-yl]pyrazin-2-yl]-N,N-dimethylbenzamide	1296842: Inhibition of N-terminal 6His-tagged recombinant human full length wild type MNK2b using biotin-SGSGKRREILSRRPSYR-NH2 as substrate after 1 hr by HTRF assay	ic50	0.0007	uM
[(3R)-3-aminopiperidin-1-yl]-[4-[3-(1-benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]phenyl]methanone	2083031: Inhibition of recombinant MNK2 (unknown origin) using TATKSGSTTKNR as substrate preincubated for 15 mins followed by ATP addition and measured after 1 hr by ADP-glo kinase assay	ic50	0.0007	uM
6-[(6-aminopyrimidin-4-yl)amino]-8-methylspiro[2H-imidazo[1,5-a]pyridine-3,1’-cyclohexane]-1,5-dione	1479625: Inhibition of full length N-terminal GST-tagged recombinant human MNK2 expressed in baculovirus expression system using Ac-TATKSGSTTKNR-NH2 as substrate preincubated for 5 mins followed by ATP addition measured after 40 mins by ADP-Glo assay	ic50	0.0010	uM
6-[(6-aminopyrimidin-4-yl)amino]-8-methylspiro[2H-imidazo[1,5-a]pyridine-3,1’-cyclohexane]-1,5-dione;hydrochloride	1534878: Inhibition of MNK2 (unknown origin) expressed in HEK293 cells assessed as decrease in eIF4E phosphorylation at Ser209 residues by Western blot analysis	ic50	0.0010	uM
6-[(6-aminopyrimidin-4-yl)amino]-4’,4’-difluoro-8-methylspiro[2H-imidazo[1,5-a]pyridine-3,1’-cyclohexane]-1,5-dione	1479625: Inhibition of full length N-terminal GST-tagged recombinant human MNK2 expressed in baculovirus expression system using Ac-TATKSGSTTKNR-NH2 as substrate preincubated for 5 mins followed by ATP addition measured after 40 mins by ADP-Glo assay	ic50	0.0010	uM
3-[5-amino-6-(1-methyl-7-piperazin-1-ylbenzimidazol-2-yl)pyrazin-2-yl]-N,N-dimethylbenzamide	1296842: Inhibition of N-terminal 6His-tagged recombinant human full length wild type MNK2b using biotin-SGSGKRREILSRRPSYR-NH2 as substrate after 1 hr by HTRF assay	ic50	0.0010	uM
8-chloro-3,3-dimethyl-6-(pyrimidin-4-ylamino)-2H-imidazo[1,5-a]pyridine-1,5-dione	1479625: Inhibition of full length N-terminal GST-tagged recombinant human MNK2 expressed in baculovirus expression system using Ac-TATKSGSTTKNR-NH2 as substrate preincubated for 5 mins followed by ATP addition measured after 40 mins by ADP-Glo assay	ic50	0.0012	uM
N-[6-[[8-chloro-3-(3-chlorophenyl)-3-methyl-1,5-dioxo-2H-imidazo[1,5-a]pyridin-6-yl]amino]pyrimidin-4-yl]cyclopropanecarboxamide	1479625: Inhibition of full length N-terminal GST-tagged recombinant human MNK2 expressed in baculovirus expression system using Ac-TATKSGSTTKNR-NH2 as substrate preincubated for 5 mins followed by ATP addition measured after 40 mins by ADP-Glo assay	ic50	0.0012	uM
[4-[3-(1-benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]phenyl]-[4-(dimethylamino)piperidin-1-yl]methanone	2083031: Inhibition of recombinant MNK2 (unknown origin) using TATKSGSTTKNR as substrate preincubated for 15 mins followed by ATP addition and measured after 1 hr by ADP-glo kinase assay	ic50	0.0012	uM
[4-[3-(1-benzofuran-2-yl)imidazo[1,2-a]pyridin-6-yl]phenyl]-[4-(dimethylamino)piperidin-1-yl]methanone	2083031: Inhibition of recombinant MNK2 (unknown origin) using TATKSGSTTKNR as substrate preincubated for 15 mins followed by ATP addition and measured after 1 hr by ADP-glo kinase assay	ic50	0.0013	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	507624: Binding affinity to MKNK2	kd	0.0014	uM
[4-[4-(2,3-dihydroindol-1-yl)pyrido[3,2-d]pyrimidin-6-yl]phenyl]-morpholin-4-ylmethanone	2064722: Inhibition of Mnk2 (unknown origin) incubated for 60 mins in presence of ATP/substrateby HTRF assay	ic50	0.0014	uM
8-chloro-6-(pyrimidin-4-ylamino)spiro[2H-imidazo[1,5-a]pyridine-3,1’-cyclohexane]-1,5-dione	1552931: Competitive inhibition of recombinant His-tagged MNK2 (unknown origin) using eIF4E derived peptide as substrate at concentration of Km/10 in presence of ATP by ADP-Glo assay	ic50	0.0015	uM
[(3S)-3-aminopiperidin-1-yl]-[4-[3-(1-benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]phenyl]methanone	2083031: Inhibition of recombinant MNK2 (unknown origin) using TATKSGSTTKNR as substrate preincubated for 15 mins followed by ATP addition and measured after 1 hr by ADP-glo kinase assay	ic50	0.0015	uM
[4-(3-isoquinolin-6-ylimidazo[1,2-a]pyridin-6-yl)phenyl]-(4-piperidin-1-ylpiperidin-1-yl)methanone	1763881: Inhibition of N-terminal GST-fused human full length recombinant MNK2 (1 to 465 residues) expressed in baculovirus-infected Sf21 cells using TATKSGSTTKNR as substrate preincubated with enzyme and substrate for 10 mins followed by ATP addition and measured after 40 mins by ADP-glo luminescence assay	ic50	0.0015	uM
[3-[4-(2,3-dihydroindol-1-yl)pyrido[3,2-d]pyrimidin-6-yl]phenyl]-piperazin-1-ylmethanone	2064722: Inhibition of Mnk2 (unknown origin) incubated for 60 mins in presence of ATP/substrateby HTRF assay	ic50	0.0015	uM
[4-[4-(2,3-dihydroindol-1-yl)pyrido[3,2-d]pyrimidin-6-yl]phenyl]-piperazin-1-ylmethanone	2064722: Inhibition of Mnk2 (unknown origin) incubated for 60 mins in presence of ATP/substrateby HTRF assay	ic50	0.0016	uM
[(3R)-3-aminopiperidin-1-yl]-[4-[3-(1-benzofuran-2-yl)imidazo[1,2-a]pyridin-6-yl]phenyl]methanone	2083031: Inhibition of recombinant MNK2 (unknown origin) using TATKSGSTTKNR as substrate preincubated for 15 mins followed by ATP addition and measured after 1 hr by ADP-glo kinase assay	ic50	0.0016	uM
[3-[4-(2,3-dihydroindol-1-yl)pyrido[3,2-d]pyrimidin-6-yl]phenyl]-morpholin-4-ylmethanone	2064722: Inhibition of Mnk2 (unknown origin) incubated for 60 mins in presence of ATP/substrateby HTRF assay	ic50	0.0018	uM
[(3S)-3-aminopiperidin-1-yl]-[4-[4-(2,3-dihydroindol-1-yl)pyrido[3,2-d]pyrimidin-6-yl]phenyl]methanone	2064722: Inhibition of Mnk2 (unknown origin) incubated for 60 mins in presence of ATP/substrateby HTRF assay	ic50	0.0019	uM
3-[6-amino-5-(4-piperazin-1-yl-1H-benzimidazol-2-yl)-3-pyridinyl]-N,N-dimethylbenzamide	1296842: Inhibition of N-terminal 6His-tagged recombinant human full length wild type MNK2b using biotin-SGSGKRREILSRRPSYR-NH2 as substrate after 1 hr by HTRF assay	ic50	0.0020	uM
N-[3-(dimethylamino)propyl]-7-(5-fluoro-2,3-dihydroindol-1-yl)-[1,3]thiazolo[5,4-d]pyrimidine-2-carboxamide	1881761: Inhibition of Mnk2 (unknown origin)	ic50	0.0020	uM
[4-[3-(1-benzofuran-2-yl)imidazo[1,2-a]pyrazin-6-yl]phenyl]-morpholin-4-ylmethanone	2083031: Inhibition of recombinant MNK2 (unknown origin) using TATKSGSTTKNR as substrate preincubated for 15 mins followed by ATP addition and measured after 1 hr by ADP-glo kinase assay	ic50	0.0020	uM
[4-[3-(1-benzofuran-2-yl)imidazo[1,2-a]pyridin-6-yl]phenyl]-(4-methylpiperazin-1-yl)methanone	2083031: Inhibition of recombinant MNK2 (unknown origin) using TATKSGSTTKNR as substrate preincubated for 15 mins followed by ATP addition and measured after 1 hr by ADP-glo kinase assay	ic50	0.0022	uM
N-[6-[(3,3-dimethyl-1,5-dioxo-2H-imidazo[1,5-a]pyridin-6-yl)amino]pyrimidin-4-yl]cyclopropanecarboxamide	1479625: Inhibition of full length N-terminal GST-tagged recombinant human MNK2 expressed in baculovirus expression system using Ac-TATKSGSTTKNR-NH2 as substrate preincubated for 5 mins followed by ATP addition measured after 40 mins by ADP-Glo assay	ic50	0.0023	uM
[(3R)-3-aminopiperidin-1-yl]-[4-[4-(2,3-dihydroindol-1-yl)pyrido[3,2-d]pyrimidin-6-yl]phenyl]methanone	2064722: Inhibition of Mnk2 (unknown origin) incubated for 60 mins in presence of ATP/substrateby HTRF assay	ic50	0.0023	uM
7-(3,3-dimethyl-2H-indol-1-yl)-N-(piperidin-4-ylmethyl)-[1,3]thiazolo[5,4-d]pyrimidine-2-carboxamide	1881761: Inhibition of Mnk2 (unknown origin)	ic50	0.0025	uM
[(3S)-3-aminopiperidin-1-yl]-[4-(3-isoquinolin-6-ylimidazo[1,2-a]pyridin-6-yl)phenyl]methanone	1763881: Inhibition of N-terminal GST-fused human full length recombinant MNK2 (1 to 465 residues) expressed in baculovirus-infected Sf21 cells using TATKSGSTTKNR as substrate preincubated with enzyme and substrate for 10 mins followed by ATP addition and measured after 40 mins by ADP-glo luminescence assay	ic50	0.0025	uM
[4-[3-(1-benzofuran-2-yl)imidazo[1,2-a]pyridin-6-yl]phenyl]-piperazin-1-ylmethanone	2083031: Inhibition of recombinant MNK2 (unknown origin) using TATKSGSTTKNR as substrate preincubated for 15 mins followed by ATP addition and measured after 1 hr by ADP-glo kinase assay	ic50	0.0025	uM
8-fluoro-3,3-dimethyl-6-(pyrimidin-4-ylamino)-2H-imidazo[1,5-a]pyridine-1,5-dione	1479625: Inhibition of full length N-terminal GST-tagged recombinant human MNK2 expressed in baculovirus expression system using Ac-TATKSGSTTKNR-NH2 as substrate preincubated for 5 mins followed by ATP addition measured after 40 mins by ADP-Glo assay	ic50	0.0026	uM
4-[4-(2,3-dihydroindol-1-yl)pyrido[3,2-d]pyrimidin-6-yl]-N-(3-hydroxypropyl)benzamide	2064722: Inhibition of Mnk2 (unknown origin) incubated for 60 mins in presence of ATP/substrateby HTRF assay	ic50	0.0029	uM
[4-(3-isoquinolin-6-ylimidazo[1,2-a]pyridin-6-yl)phenyl]-piperazin-1-ylmethanone	1763881: Inhibition of N-terminal GST-fused human full length recombinant MNK2 (1 to 465 residues) expressed in baculovirus-infected Sf21 cells using TATKSGSTTKNR as substrate preincubated with enzyme and substrate for 10 mins followed by ATP addition and measured after 40 mins by ADP-glo luminescence assay	ic50	0.0029	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	435531: Binding constant for MKNK2 kinase domain	kd	0.0030	uM
[4-[3-(1-benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]phenyl]-(4-morpholin-4-ylpiperidin-1-yl)methanone	2083031: Inhibition of recombinant MNK2 (unknown origin) using TATKSGSTTKNR as substrate preincubated for 15 mins followed by ATP addition and measured after 1 hr by ADP-glo kinase assay	ic50	0.0031	uM
7-(5-chloro-2,3-dihydroindol-1-yl)-N-(piperidin-4-ylmethyl)-[1,3]thiazolo[5,4-d]pyrimidine-2-carboxamide	1881761: Inhibition of Mnk2 (unknown origin)	ic50	0.0032	uM
[4-(3-isoquinolin-6-ylimidazo[1,2-a]pyridin-6-yl)phenyl]-(4-morpholin-4-ylpiperidin-1-yl)methanone	1763881: Inhibition of N-terminal GST-fused human full length recombinant MNK2 (1 to 465 residues) expressed in baculovirus-infected Sf21 cells using TATKSGSTTKNR as substrate preincubated with enzyme and substrate for 10 mins followed by ATP addition and measured after 40 mins by ADP-glo luminescence assay	ic50	0.0032	uM
[4-[3-(1-benzofuran-2-yl)imidazo[1,2-a]pyridin-6-yl]phenyl]-(4-morpholin-4-ylpiperidin-1-yl)methanone	2083031: Inhibition of recombinant MNK2 (unknown origin) using TATKSGSTTKNR as substrate preincubated for 15 mins followed by ATP addition and measured after 1 hr by ADP-glo kinase assay	ic50	0.0033	uM
[(3S)-3-aminopiperidin-1-yl]-[4-(3-isoquinolin-6-ylimidazo[1,2-b]pyridazin-6-yl)phenyl]methanone	1763881: Inhibition of N-terminal GST-fused human full length recombinant MNK2 (1 to 465 residues) expressed in baculovirus-infected Sf21 cells using TATKSGSTTKNR as substrate preincubated with enzyme and substrate for 10 mins followed by ATP addition and measured after 40 mins by ADP-glo luminescence assay	ic50	0.0034	uM
[3-[4-(5-fluoro-2,3-dihydroindol-1-yl)pyrido[3,2-d]pyrimidin-6-yl]phenyl]-piperazin-1-ylmethanone	2064722: Inhibition of Mnk2 (unknown origin) incubated for 60 mins in presence of ATP/substrateby HTRF assay	ic50	0.0035	uM
[(3S)-3-aminopyrrolidin-1-yl]-[4-[4-(2,3-dihydroindol-1-yl)pyrido[3,2-d]pyrimidin-6-yl]phenyl]methanone	2064722: Inhibition of Mnk2 (unknown origin) incubated for 60 mins in presence of ATP/substrateby HTRF assay	ic50	0.0036	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression, affects cotreatment, increases abundance, increases expression	6
Estradiol	affects cotreatment, decreases expression, increases expression	3
bisphenol A	increases expression	2
(+)-JQ1 compound	increases expression	2
Acetaminophen	increases expression	2
Arsenic	increases expression, affects cotreatment, increases abundance	2
Quercetin	increases expression, decreases expression	2
Valproic Acid	affects expression, increases methylation	2
Cyclosporine	increases expression	2
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
deoxynivalenol	decreases expression	1
sodium arsenate	increases abundance, increases expression	1
trichostatin A	affects expression	1
beta-lapachone	increases expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
cobaltous chloride	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
benzo(e)pyrene	decreases methylation	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	decreases expression, affects cotreatment	1
perfluorooctane sulfonic acid	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
bisphenol AF	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases activity, increases phosphorylation, increases reaction, decreases response to substance	1

ChEMBL screening assays

519 unique, capped per target: 518 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3803169	Binding	Inhibition of MNK1/2 in human KMS11-luc cells assessed as inhibition of EIF4E phosphorylation at S209 after 3 hrs by quantitative electrochemiluminescence assay	Discovery of a Selective and Potent Inhibitor of Mitogen-Activated Protein Kinase-Interacting Kinases 1 and 2 (MNK1/2) Utilizing Structure-Based Drug Design. — J Med Chem
CHEMBL1963786	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: MKNK2	PubChem BioAssay data set

Cellosaurus cell lines

7 cell lines: 5 cancer cell line, 2 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3B1	Abcam HEK293T MKNK2 KO	Transformed cell line	Female
CVCL_D7V4	Ubigene A-549 MKNK2 KO	Cancer cell line	Male
CVCL_D8QN	Ubigene HCT 116 MKNK2 KO	Cancer cell line	Male
CVCL_D9KD	Ubigene HEK293 MKNK2 KO	Transformed cell line	Female
CVCL_E0I5	Ubigene HeLa MKNK2 KO	Cancer cell line	Female
CVCL_SY50	HAP1 MKNK2 (-) 1	Cancer cell line	Male
CVCL_SY51	HAP1 MKNK2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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