MAPKAPK2

Summary

MAPKAPK2 (MAPK activated protein kinase 2, HGNC:6887) is a protein-coding gene on chromosome 1q32.1, encoding MAP kinase-activated protein kinase 2 (P49137). Stress-activated serine/threonine-protein kinase involved in cytokine production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation.

This gene encodes a member of the Ser/Thr protein kinase family. This kinase is regulated through direct phosphorylation by p38 MAP kinase. In conjunction with p38 MAP kinase, this kinase is known to be involved in many cellular processes including stress and inflammatory responses, nuclear export, gene expression regulation and cell proliferation. Heat shock protein HSP27 was shown to be one of the substrates of this kinase in vivo. Two transcript variants encoding two different isoforms have been found for this gene.

Source: NCBI Gene 9261 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 58 total
• Druggable target: yes — 29 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_032960

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6887
Approved symbol	MAPKAPK2
Name	MAPK activated protein kinase 2
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	MK2
Ensembl gene	ENSG00000162889
Ensembl biotype	protein_coding
OMIM	602006
Entrez	9261

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000294981, ENST00000367103, ENST00000479009, ENST00000493447, ENST00000916346, ENST00000943400, ENST00000943401, ENST00000943402

RefSeq mRNA: 2 — MANE Select: NM_032960 NM_004759, NM_032960

CCDS: CCDS1466, CCDS31001

Canonical transcript exons

ENST00000367103 — 10 exons

Exon	Start	End
ENSE00001069544	206731138	206731262
ENSE00001069545	206728710	206728849
ENSE00001069547	206729035	206729099
ENSE00001069548	206729396	206729475
ENSE00001069550	206731640	206731725
ENSE00001069551	206729972	206730098
ENSE00001069552	206731839	206731919
ENSE00001443498	206732575	206734281
ENSE00001648220	206730688	206730763
ENSE00001825387	206684905	206685508

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 98.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 67.1064 / max 1419.2262, expressed in 1824 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
8136	55.4572	1822
8137	4.8983	1346
8139	3.4498	1418
8135	1.8947	1237
8138	0.6971	290
8149	0.4512	230
8144	0.1315	13
8143	0.0832	4
8145	0.0220	4
8150	0.0137	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	98.54	gold quality
right atrium auricular region	UBERON:0006631	97.98	gold quality
heart left ventricle	UBERON:0002084	97.92	gold quality
cardiac atrium	UBERON:0002081	97.82	gold quality
cardiac ventricle	UBERON:0002082	97.82	gold quality
gastrocnemius	UBERON:0001388	97.61	gold quality
heart	UBERON:0000948	97.19	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.17	gold quality
muscle of leg	UBERON:0001383	97.13	gold quality
left ventricle myocardium	UBERON:0006566	96.95	gold quality
stromal cell of endometrium	CL:0002255	96.93	gold quality
muscle organ	UBERON:0001630	96.37	gold quality
upper lobe of left lung	UBERON:0008952	96.31	gold quality
right lung	UBERON:0002167	96.27	gold quality
islet of Langerhans	UBERON:0000006	96.13	gold quality
left adrenal gland cortex	UBERON:0035825	95.94	gold quality
gall bladder	UBERON:0002110	95.90	gold quality
left uterine tube	UBERON:0001303	95.87	gold quality
upper lobe of lung	UBERON:0008948	95.84	gold quality
left adrenal gland	UBERON:0001234	95.81	gold quality
type B pancreatic cell	CL:0000169	95.80	silver quality
adrenal cortex	UBERON:0001235	95.80	gold quality
granulocyte	CL:0000094	95.65	gold quality
right adrenal gland	UBERON:0001233	95.63	gold quality
right adrenal gland cortex	UBERON:0035827	95.63	gold quality
body of stomach	UBERON:0001161	95.62	gold quality
bone marrow cell	CL:0002092	95.50	gold quality
popliteal artery	UBERON:0002250	95.41	gold quality
tibial artery	UBERON:0007610	95.41	gold quality
cardiac muscle of right atrium	UBERON:0003379	95.39	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	44.53
E-HCAD-6	yes	34.03
E-MTAB-9067	yes	18.46
E-ANND-3	yes	16.04
E-CURD-112	yes	14.66
E-CURD-122	yes	12.73
E-MTAB-8498	yes	12.64
E-MTAB-9467	yes	12.42
E-GEOD-110499	no	806.70

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, ATF1, NEUROD1, STAT1

miRNA regulators (miRDB)

125 targeting MAPKAPK2, 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-8485	100.00	77.57	4731
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
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-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-651-3P	99.94	73.48	5177

Literature-anchored findings (GeneRIF, showing 40)

• Examination of the kinetic mechanism (PMID:12147348)
• structure suggests a bifunctional switch that couples kinase activation with nuclear export (PMID:12171911)
• role in pathway that promotes urokinase plasminogen activator mRNA stability in invasive breast cancer cells (PMID:12377770)
• MAPKAPK-2 and ERKs activate 5-lipoxygenase (PMID:12751751)
• crystal structures of a catalytically active C-terminal deletion form of human MAP KAP kinase 2, residues 41-364, in complex with staurosporine at 2.7 A and with ADP at 3.2 A (PMID:12791252)
• MK2 is activated with p66(ShcA) co-expression and p66(ShcA) is an in vitro substrate for MK2, further demonstrating their association and suggesting a biological role for p66(Shc) in MK2 activation (PMID:15094067)
• BAG2 was directly phosphorylated at serine 20 in vitro by MAPKAPK2 and MAPKAP2 is also required for phosphorylation of BAG2 in vivo. (PMID:15271996)
• The 30-amino acid docking domain peptide of MAPKAPK2 isoform a (MK2a) is required for the formation of a tight, functional p38alpha-MK2a signaling complex. (PMID:15287722)
• MAPKAP kinase-2 is directly responsible for Cdc25B/C phosphorylation and 14-3-3 binding in vitro and in response to UV-induced DNA damage. (PMID:15629715)
• Kaposin B reverses the instability of cytokine trnscripts by binding to and activating mitogen-activated protein kinase-associated protein kinase 2, a target of the p38 mitogen-activated protein kinase signaling pathway and inhibitor of ARE-mRNA decay (PMID:15692053)
• HSF1 phosphorylation by MAPK-activated protein kinase 2 on serine 121, inhibits transcriptional activity and promotes HSP90 binding (PMID:16278218)
• Both MAPKAPK2 and HSP27 are necessary for TGFbeta-mediated increases in MMP-2 and cell invasion in human prostate cancer. (PMID:16407830)
• Increased activation of MAPKAP2 is responsible for elevated and posttranscriptionally regulated TNF-alpha protein expression in psoriatic skin. (PMID:16424170)
• A role is proposed for MAPKAPK2 in a transgenic mouse model of neuroinflammatory and neurodegenerative pathology of relevance to Alzheimer disease. (PMID:16774924)
• MAPKAP kinase-2 phosphorylates CDC25B on multiple sites including S169, S323, S353 and S375, while p38SAPK phosphorylates CDC25B on S249. (PMID:16861915)
• Binding of MAPK14 (p38alpha): the C-terminal regulatory domain of MK2 binds in the docking groove of p38alpha, and the ATP-binding sites of both kinases are at the heterodimer interface. (PMID:17255097)
• MK2-regulated LSP1 phosphorylation is involved in stabilization of F-actin polarization during neutrophil chemotaxis. (PMID:17481585)
• MK2-mediated inhibition of BRF1 requires phosphorylation at S54, S92, and S203. (PMID:18326031)
• Upregulated in at least 50% of multiple myeloma cases tested. (PMID:19171422)
• Data provide evidence that p38 Map kinase pathway is activated leading to increased upregulation of mixed lineage kinase 3, MKK3/6, MSK1, and Mapkapk2, upon treatment of BCR/ABL expressing cells with dasatinib (PMID:19672773)
• From a siRNA screen of the human kinome adapted to a high-throughput format, we found that knock-down of the MAPK-activated protein kinase 2 (MK2), a downstream target of the p38 MAPK, protected against Shiga toxicity. (PMID:19951368)
• Findings implicate p38 MAPK and MAPKAPK2 in mediating bladder cancer invasion via regulation of MMP-2 and MMP-9 at the level of mRNA stability. (PMID:20068172)
• MK2 signaling has a minor role in skin inflammation [commentary] (PMID:20081887)
• miR-34c is a critical regulator of c-Myc expression following DNA damage acting downstream of p38 MAPK/MK2, and miR-34c serves to remove c-Myc to prevent inappropriate replication which may otherwise lead to genomic instability. (PMID:20212154)
• Tumor necrosis factor (TNF)-alpha protein, but not messenger RNA production, is markedly impaired by MK2 deficiency of transgenic mice. (PMID:20375303)
• MK2 phosphorylation reduces the ability of TTP to promote deadenylation by inhibiting the recruitment of CAF1 deadenylase in a mechanism that does not involve sequestration of TTP by 14-3-3. (PMID:20595389)
• Demonstrate a critical role for the MK2 pathway in the posttranscriptional regulation of gene expression as part of the DNA damage response in cancer cells. (PMID:20932473)
• Data suggest that phosphorylation of tristetraprolin by MK2 primarily affects mRNA decay downstream of RNA binding by preventing recruitment of the deadenylation machinery. (PMID:21078877)
• MK2 SUMOylation is a new mechanism for regulating actin filament dynamics in ECs. (PMID:21131586)
• Data show that DNA damage stimulates the formation of a cytosolic complex of ATM, NEMO, RIP1, and TAK1, and that TAK1 mediates the NF-kappaB and p38 mitogen-activated protein kinase (MAPK)/MAPK-activated protein 2 responses to DNA damage. (PMID:21606198)
• analysis of inhibition of human MK2 (PMID:22119462)
• TLR3 induces signaling mechanisms involving TRIF, p38 MAPK and MK2 to enhance stabilization of IFN-beta mRNA contributing to enhanced IFN-beta levels during pathogen infections. (PMID:22200507)
• The results suggest that in human pulmonary microvascular endothelial cells, MAP-kinase-activated kinase 2 regulates TNF-alpha-induced expression of ICAM-1 and IL-8 via tristetraprolin at the mRNA decay level. (PMID:22268119)
• Data show that MAPKAP kinase 2 overexpression is associated with expression of p38 MAP kinase and ETV1 in gastrointestinal stromal tumors (GIST). (PMID:22351694)
• A functional copy-number variation in MAPKAPK2 predicts risk and prognosis of lung cancer (PMID:22883146)
• Cigarette smoke and its component acrolein augment IL-8/CXCL8 mRNA stability via p38 MAPK/MK2 signaling in human pulmonary cells. (PMID:22983351)
• The human respiratory syncytial virus-induced sequestration of p38-P in IBs resulted in a substantial reduction in the accumulation of a downstream signaling substrate, MAPK-activated protein kinase 2 (MK2). (PMID:23152511)
• activation of PP2A or inactivation of the p38MAPK-MAPKAPK2-Hsp27 has a role in survival of cancer stem cells under hypoxia and serum depletion via decrease in PP2A activity (PMID:23185379)
• MAPK-activated protein kinase-2 limits endothelial inflammation via the PIAS1 S522 phosphorylation-mediated increase in PIAS1 transrepression and SUMO ligase activity. (PMID:23202365)
• This study showed that MK2 kinase is activated by TcdA and TcdB and regulates the expression of proinflammatory cytokines. (PMID:23264053)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mapkapk2a	ENSDARG00000002552
danio_rerio	mapkapk2b	ENSDARG00000018530
mus_musculus	Mapkapk2	ENSMUSG00000016528
rattus_norvegicus	Mapkapk2	ENSRNOG00000004726

Paralogs (6): DCX (ENSG00000077279), MKNK1 (ENSG00000079277), MAPKAPK5 (ENSG00000089022), MKNK2 (ENSG00000099875), MAPKAPK3 (ENSG00000114738), CAMK4 (ENSG00000152495)

Protein

Protein identifiers

MAP kinase-activated protein kinase 2 — P49137 (reviewed: P49137)

All UniProt accessions (1): P49137

UniProt curated annotations — full annotation on UniProt →

Function. Stress-activated serine/threonine-protein kinase involved in cytokine production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, CEP131, ELAVL1, HNRNPA0, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Phosphorylates HSF1; leading to the interaction with HSP90 proteins and inhibiting HSF1 homotrimerization, DNA-binding and transactivation activities. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to the dissociation of HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impairment of their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading to the regulation of the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity, leading to inhibition of dependent degradation of ARE-containing transcripts. Phosphorylates CEP131 in response to cellular stress induced by ultraviolet irradiation which promotes binding of CEP131 to 14-3-3 proteins and inhibits formation of novel centriolar satellites. Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading to stabilization of GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3.

Subunit / interactions. Heterodimer with p38-alpha/MAPK14; this heterodimer forms a stable complex: molecules are positioned ‘face to face’ so that the ATP-binding sites of both kinases are at the heterodimer interface. Interacts with PHC2. Interacts with HSF1.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Expressed in all tissues examined.

Post-translational modifications. Sumoylation inhibits the protein kinase activity. Phosphorylated and activated by MAP kinase p38-alpha/MAPK14 at Thr-222, Ser-272 and Thr-334.

Activity regulation. Activated following phosphorylation by p38-alpha/MAPK14 following various stresses. Inhibited following sumoylation. Specifically inhibited by pyrrolopyridine inhibitors.

Miscellaneous. Has a nuclear localization signal.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P49137-1	1	yes
P49137-2	2

RefSeq proteins (2): NP_004750, NP_116584* (*=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
IPR027442	MAPKAPK_C	Homologous_superfamily

Pfam: PF00069

Enzyme classification (BRENDA):

• EC 2.7.11.1 — non-specific serine/threonine protein kinase (BRENDA: 71 organisms, 682 substrates, 228 inhibitors, 23 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0007–0.64	11
KKRAARATSNVFA	0.013–0.045	3
PAH1 PHOSPHATIDATE PHOSPHATASE	0.0002	2
RRRLSSLRA	0.0036–0.0037	2
GTP	0.46	1
KKRAARASSNVFA	0.02	1
LYS-LYS-PHE-ASN-ARG-THR-LEU-SER-VAL-ALA	0.0093	1
MYELIN BASIC PROTEIN	0.145	1

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 (76 total): helix 21, strand 16, mutagenesis site 11, modified residue 6, binding site 3, region of interest 3, turn 3, short sequence motif 3, sequence variant 2, sequence conflict 2, chain 1, domain 1, cross-link 1, splice variant 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

31 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
2OKR	X-RAY DIFFRACTION	2
3M2W	X-RAY DIFFRACTION	2.41
3KGA	X-RAY DIFFRACTION	2.55
8XX1	X-RAY DIFFRACTION	2.55
3M42	X-RAY DIFFRACTION	2.68
1NXK	X-RAY DIFFRACTION	2.7
2OZA	X-RAY DIFFRACTION	2.7
1KWP	X-RAY DIFFRACTION	2.8
6T8X	X-RAY DIFFRACTION	2.81
2PZY	X-RAY DIFFRACTION	2.9
3A2C	X-RAY DIFFRACTION	2.9
3KA0	X-RAY DIFFRACTION	2.9
3KC3	X-RAY DIFFRACTION	2.9
3R2B	X-RAY DIFFRACTION	2.9
3WI6	X-RAY DIFFRACTION	2.99
1NY3	X-RAY DIFFRACTION	3
3R2Y	X-RAY DIFFRACTION	3
4TYH	X-RAY DIFFRACTION	3
9R59	X-RAY DIFFRACTION	3
2JBO	X-RAY DIFFRACTION	3.1
3GOK	X-RAY DIFFRACTION	3.2
3R30	X-RAY DIFFRACTION	3.2
3FPM	X-RAY DIFFRACTION	3.3
2JBP	X-RAY DIFFRACTION	3.31
8XU4	X-RAY DIFFRACTION	3.4
3FYK	X-RAY DIFFRACTION	3.5
6TCA	X-RAY DIFFRACTION	3.7
2P3G	X-RAY DIFFRACTION	3.8
3FYJ	X-RAY DIFFRACTION	3.8
7NRY	X-RAY DIFFRACTION	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49137-F1	83.08	0.59

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): 186 (proton acceptor)

Ligand- & substrate-binding residues (3): 70–78; 93; 139–141

Post-translational modifications (7): 9, 25, 222, 272, 328, 334, 353

Mutagenesis-validated functional residues (11):

Position	Phenotype
93	kinase defective mutant, abolishes activity.
207	kinase defective mutant, abolishes activity.
222	strong decrease in kinase activity.
222	mimicks phosphorylation state, leading to slight increase of basal kinase activity.
222	mimicks phosphorylation state and constitutive protein kinase activity; when associated with e-334.
272	strong decrease in kinase activity.
272	mimicks phosphorylation state, leading to slight increase of basal kinase activity.
334	slight decrease in kinase activity.
334	mimicks phosphorylation state, leading to elevated basal kinase activity.
334	mimicks phosphorylation state and constitutive protein kinase activity; when associated with e-222.
353	induces decreased sumoylation and increase in protein kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

53 pathways

ID	Pathway
R-HSA-171007	p38MAPK events
R-HSA-199920	CREB phosphorylation
R-HSA-2142691	Synthesis of Leukotrienes (LT) and Eoxins (EX)
R-HSA-2559580	Oxidative Stress Induced Senescence
R-HSA-3371453	Regulation of HSF1-mediated heat shock response
R-HSA-4420097	VEGFA-VEGFR2 Pathway
R-HSA-450302	activated TAK1 mediates p38 MAPK activation
R-HSA-450385	Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA
R-HSA-450513	Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA
R-HSA-5357905	Regulation of TNFR1 signaling
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1430728	Metabolism
R-HSA-162582	Signal Transduction
R-HSA-166016	Toll Like Receptor 4 (TLR4) Cascade
R-HSA-166058	MyD88:MAL(TIRAP) cascade initiated on plasma membrane
R-HSA-166166	MyD88-independent TLR4 cascade
R-HSA-166520	Signaling by NTRKs
R-HSA-167044	Signalling to RAS
R-HSA-168138	Toll Like Receptor 9 (TLR9) Cascade
R-HSA-168142	Toll Like Receptor 10 (TLR10) Cascade
R-HSA-168164	Toll Like Receptor 3 (TLR3) Cascade
R-HSA-168176	Toll Like Receptor 5 (TLR5) Cascade
R-HSA-168179	Toll Like Receptor TLR1:TLR2 Cascade
R-HSA-168181	Toll Like Receptor 7/8 (TLR7/8) Cascade
R-HSA-168188	Toll Like Receptor TLR6:TLR2 Cascade
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-168898	Toll-like Receptor Cascades
R-HSA-181438	Toll Like Receptor 2 (TLR2) Cascade
R-HSA-187037	Signaling by NTRK1 (TRKA)

MSigDB gene sets: 361 (showing top): ELVIDGE_HYPOXIA_DN, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, AAGCAAT_MIR137, GOBP_PINOCYTOSIS, REACTOME_INNATE_IMMUNE_SYSTEM, YAGI_AML_WITH_INV_16_TRANSLOCATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, KEGG_MAPK_SIGNALING_PATHWAY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_3_UTR_MEDIATED_MRNA_STABILIZATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_VASCULAR_ENDOTHELIAL_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY

GO Biological Process (23): MAPK cascade (GO:0000165), toll-like receptor signaling pathway (GO:0002224), leukotriene metabolic process (GO:0006691), inflammatory response (GO:0006954), DNA damage response (GO:0006974), regulation of tumor necrosis factor-mediated signaling pathway (GO:0010803), response to lipopolysaccharide (GO:0032496), regulation of interleukin-6 production (GO:0032675), regulation of tumor necrosis factor production (GO:0032680), positive regulation of tumor necrosis factor production (GO:0032760), response to cytokine (GO:0034097), intracellular signal transduction (GO:0035556), cellular response to vascular endothelial growth factor stimulus (GO:0035924), p38MAPK cascade (GO:0038066), regulation of mRNA stability (GO:0043488), macropinocytosis (GO:0044351), vascular endothelial growth factor receptor signaling pathway (GO:0048010), inner ear development (GO:0048839), positive regulation of macrophage cytokine production (GO:0060907), 3’-UTR-mediated mRNA stabilization (GO:0070935), regulation of cellular response to heat (GO:1900034), protein phosphorylation (GO:0006468), mRNA stabilization (GO:0048255)

GO Molecular Function (12): protein kinase activity (GO:0004672), 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), mitogen-activated protein kinase binding (GO:0051019), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), ciliary basal body (GO:0036064), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-17 pathways:

Category	Pathways
Toll-like Receptor Cascades	3
Regulation of mRNA stability by proteins that bind AU-rich elements	2
Toll Like Receptor 4 (TLR4) Cascade	2
Signalling to RAS	1
Nuclear Events (kinase and transcription factor activation)	1
MAPK targets/ Nuclear events mediated by MAP kinases	1
Arachidonate metabolism	1
Cellular Senescence	1
Cellular response to heat stress	1
Signaling by VEGF	1
MAP kinase activation	1
TNF signaling	1
Immune System	1
Toll Like Receptor TLR1:TLR2 Cascade	1
Toll Like Receptor TLR6:TLR2 Cascade	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
tumor necrosis factor production	2
intracellular anatomical structure	2
protein kinase activity	2
protein serine/threonine kinase activity	2
microtubule organizing center	2
intracellular signaling cassette	1
pattern recognition receptor signaling pathway	1
icosanoid metabolic process	1
defense response	1
cellular response to stress	1
regulation of cytokine-mediated signaling pathway	1
tumor necrosis factor-mediated signaling pathway	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
regulation of cytokine production	1
interleukin-6 production	1
regulation of tumor necrosis factor superfamily cytokine production	1
regulation of tumor necrosis factor production	1
positive regulation of tumor necrosis factor superfamily cytokine production	1
response to peptide	1
signal transduction	1
cellular response to growth factor stimulus	1
MAPK cascade	1
regulation of RNA stability	1
regulation of mRNA catabolic process	1
pinocytosis	1
cell surface receptor protein tyrosine kinase signaling pathway	1
ear development	1
anatomical structure development	1
macrophage cytokine production	1
regulation of macrophage cytokine production	1
positive regulation of myeloid leukocyte cytokine production involved in immune response	1
mRNA stabilization	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
protein binding	1
adenyl ribonucleotide binding	1

Protein interactions and networks

STRING

1586 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAPKAPK2	HSPB1	P04792	915
MAPKAPK2	HSPB2	Q16082	821
MAPKAPK2	HSPB3	Q12988	821
MAPKAPK2	MAPK14	Q16539	692
MAPKAPK2	MAPK11	Q15759	692
MAPKAPK2	RCSD1	Q6JBY9	692
MAPKAPK2	ZFP36L1	Q07352	691
MAPKAPK2	CREB1	P16220	668
MAPKAPK2	AKT1	P31749	652
MAPKAPK2	IL1A	P01583	623
MAPKAPK2	ATF1	P18846	611
MAPKAPK2	ZFP36	P26651	611
MAPKAPK2	CDC25B	P30305	594
MAPKAPK2	CAPZA1	P52907	588
MAPKAPK2	BAG2	O95816	582

IntAct

61 interactions, top by confidence:

A	B	Type	Score
MAPK14	MAPKAPK2	psi-mi:“MI:0914”(association)	0.940
MAPK14	MAPKAPK2	psi-mi:“MI:0407”(direct interaction)	0.940
MAPKAPK2	MAPK14	psi-mi:“MI:0915”(physical association)	0.940
MAPKAPK2	MAPK14	psi-mi:“MI:2364”(proximity)	0.940
MAPK14	RPS6KA4	psi-mi:“MI:0914”(association)	0.870
MAPK14	MAP2K3	psi-mi:“MI:0914”(association)	0.800
MAPK14	OBSL1	psi-mi:“MI:0914”(association)	0.790
MAPKAPK2	MAPK11	psi-mi:“MI:0914”(association)	0.730
MAPK14	RPS6KA5	psi-mi:“MI:0914”(association)	0.660
HSF1	MAPKAPK2	psi-mi:“MI:0915”(physical association)	0.600
HSF1	MAPKAPK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.600
MAPKAPK2	HSF1	psi-mi:“MI:0915”(physical association)	0.600
MAPKAPK2	HSPB1	psi-mi:“MI:0217”(phosphorylation reaction)	0.570
HSPB1	MAPKAPK2	psi-mi:“MI:2364”(proximity)	0.570
MAPKAPK2	MTHFD2	psi-mi:“MI:0914”(association)	0.530
STAT3	MAPKAPK2	psi-mi:“MI:0915”(physical association)	0.490
MAPKAPK2	STAT3	psi-mi:“MI:0915”(physical association)	0.490
ESR1		psi-mi:“MI:0914”(association)	0.460
MAPKAPK2	CDC25A	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
AATF	MAPKAPK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
MAPKAPK2	LIMK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440

BioGRID (215): MAPKAPK2 (Biochemical Activity), MAPK14 (Affinity Capture-Western), MAPKAPK2 (Affinity Capture-Western), MAPKAPK2 (Reconstituted Complex), PIAS2 (Biochemical Activity), HSPB1 (Biochemical Activity), DDX5 (Affinity Capture-Western), MAPKAPK2 (Affinity Capture-Western), DDX5 (Biochemical Activity), MAPKAPK2 (Affinity Capture-RNA), MAPKAPK2 (Affinity Capture-RNA), LSP1 (Biochemical Activity), MAPKAPK2 (Affinity Capture-MS), MAPKAPK2 (Affinity Capture-MS), TRIM28 (Biochemical Activity)

ESM2 similar proteins: A0A8C0TYJ0, A0A8I5ZNK2, A5D7H2, O55047, O88506, O94806, O95747, P00535, P11273, P32298, P34947, P43249, P49137, Q08CW1, Q12959, Q13033, Q15139, Q15700, Q16644, Q1ECX4, Q28C55, Q3SYZ2, Q3UMW7, Q5PYH5, Q5PYH6, Q5R372, Q5R495, Q5RCW6, Q5XIS9, Q62101, Q62696, Q62833, Q63622, Q66H84, Q6P9R2, Q811D0, Q863I2, Q86UE8, Q8BZ03, Q8C0V0

Diamond homologs: A1CHL6, A1CX69, A2QIL5, A6RYB8, A6ZU07, A7F0W2, A7KAL2, A7TIZ4, B2DD29, D3ZHP7, D7UQM5, F4I1N8, F4IRW0, F4JBP3, I1RNG8, J4W0G2, O22932, O22971, O65554, O70405, O75385, O80902, P0CP70, P0CP71, P22209, P49136, P49137, P49138, P53104, P87248, P92958, Q0CLX3, Q0D4B2, Q0JI49, Q0UY20, Q1DN93, Q23023, Q2H6X2, Q2QAV0, Q2UGZ7

SIGNOR signaling

71 interactions.

A	Effect	B	Mechanism
MAPK14	“up-regulates activity”	MAPKAPK2	phosphorylation
MAPK3	up-regulates	MAPKAPK2	phosphorylation
MAPKAPK2	up-regulates	BAG2	phosphorylation
MAPKAPK2	“up-regulates quantity by stabilization”	MDM2	phosphorylation
MAPKAPK2	unknown	RTN4	phosphorylation
MAPKAPK2	up-regulates	LIMK1	phosphorylation
MAPKAPK2	down-regulates	CDC25A	phosphorylation
MAPKAPK2	up-regulates	CREB1	phosphorylation
MAPKAPK2	down-regulates	ZFP36L1	phosphorylation
MAPKAPK2	up-regulates	AGO2	phosphorylation
MAPKAPK2	“up-regulates activity”	CREB1	phosphorylation
MAPKAPK2	up-regulates	ELAVL1	phosphorylation
MAPKAPK2	up-regulates	ETV1	phosphorylation
MAPKAPK2	down-regulates	HSPB1	phosphorylation
MAPKAPK2	up-regulates	SRF	phosphorylation
MAPKAPK2	up-regulates	TCF3	phosphorylation
MAPKAPK2	down-regulates	PARN	phosphorylation
MAPKAPK2	up-regulates	PLK1	phosphorylation
MAPKAPK2	up-regulates	AATF	phosphorylation
MAPKAPK2	up-regulates	PIAS1	phosphorylation
MAPKAPK2	“down-regulates activity”	YWHAZ	phosphorylation
MAPKAPK2	“down-regulates activity”	PDE4A	phosphorylation
MAPKAPK2	“down-regulates quantity by destabilization”	UBE2J1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 47 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
MAP kinase activation	5	46.8×	1e-06
Toll Like Receptor 10 (TLR10) Cascade	6	39.2×	3e-07
Toll Like Receptor 5 (TLR5) Cascade	6	39.2×	3e-07
Interleukin-17 signaling	5	38.5×	3e-06
Toll Like Receptor TLR6:TLR2 Cascade	7	37.3×	9e-08
MyD88 cascade initiated on plasma membrane	6	37.1×	4e-07
Toll Like Receptor 2 (TLR2) Cascade	7	36.7×	9e-08
Toll Like Receptor TLR1:TLR2 Cascade	7	35.6×	9e-08

GO biological processes:

GO term	Partners	Fold	FDR
intracellular signal transduction	8	7.6×	2e-03
inflammatory response	7	6.6×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1905 predictions. Top by Δscore:

Variant	Effect	Δscore
1:206685507:AA:A	donor_gain	1.0000
1:206685507:AAGTA:A	donor_loss	1.0000
1:206685508:AG:A	donor_loss	1.0000
1:206685509:G:GG	donor_gain	1.0000
1:206728705:TGCA:T	acceptor_loss	1.0000
1:206728706:GCA:G	acceptor_loss	1.0000
1:206728708:A:AC	acceptor_loss	1.0000
1:206728708:A:AG	acceptor_gain	1.0000
1:206728708:AGAT:A	acceptor_gain	1.0000
1:206728709:G:GG	acceptor_gain	1.0000
1:206728709:GA:G	acceptor_gain	1.0000
1:206728709:GAT:G	acceptor_gain	1.0000
1:206728709:GATG:G	acceptor_gain	1.0000
1:206728709:GATGC:G	acceptor_gain	1.0000
1:206728823:G:GT	donor_gain	1.0000
1:206728845:GAATG:G	donor_gain	1.0000
1:206728846:AATG:A	donor_gain	1.0000
1:206728847:ATG:A	donor_gain	1.0000
1:206728847:ATGGT:A	donor_loss	1.0000
1:206728848:TG:T	donor_gain	1.0000
1:206728849:GG:G	donor_gain	1.0000
1:206728850:G:C	donor_loss	1.0000
1:206728850:G:GG	donor_gain	1.0000
1:206728851:T:G	donor_loss	1.0000
1:206729033:A:AG	acceptor_gain	1.0000
1:206729034:G:GG	acceptor_gain	1.0000
1:206729390:CTACA:C	acceptor_loss	1.0000
1:206729391:TACA:T	acceptor_loss	1.0000
1:206729392:A:AG	acceptor_gain	1.0000
1:206729392:ACAGA:A	acceptor_loss	1.0000

AlphaMissense

2624 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:206685440:G:A	G71R	1.000
1:206685440:G:C	G71R	1.000
1:206685440:G:T	G71W	1.000
1:206685441:G:A	G71E	1.000
1:206685446:G:C	G73R	1.000
1:206685447:G:A	G73D	1.000
1:206685455:G:C	G76R	1.000
1:206685456:G:A	G76D	1.000
1:206685456:G:T	G76V	1.000
1:206685501:C:A	A91D	1.000
1:206685504:T:C	L92P	1.000
1:206685506:A:G	K93E	1.000
1:206685508:A:C	K93N	1.000
1:206685508:A:T	K93N	1.000
1:206729052:T:C	L146P	1.000
1:206729422:G:C	G171R	1.000
1:206729423:G:A	G171D	1.000
1:206729441:T:C	L177P	1.000
1:206729459:C:A	A183D	1.000
1:206729461:C:G	H184D	1.000
1:206729463:T:A	H184Q	1.000
1:206729463:T:G	H184Q	1.000
1:206729465:G:C	R185P	1.000
1:206729467:G:C	D186H	1.000
1:206729468:A:C	D186A	1.000
1:206729468:A:G	D186G	1.000
1:206729468:A:T	D186V	1.000
1:206729469:T:A	D186E	1.000
1:206729469:T:G	D186E	1.000
1:206729471:T:A	V187D	1.000

dbSNP variants (sampled 300 via entrez): RS1000030915 (1:206712056 G>A,T), RS1000183881 (1:206707928 G>A), RS1000344518 (1:206701878 A>T), RS1000628383 (1:206703039 T>C), RS1000698161 (1:206701648 A>G), RS1000821892 (1:206696036 G>A,T), RS1000878071 (1:206689444 G>T), RS1001056382 (1:206726310 C>T), RS1001257592 (1:206714572 T>A), RS1001395967 (1:206689717 T>G), RS1001398320 (1:206708332 C>T), RS1001549899 (1:206726535 G>A), RS1001632815 (1:206695544 C>T), RS1001647984 (1:206714267 T>C), RS1001865384 (1:206702073 T>C)

Disease associations

OMIM: gene MIM:602006 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001725_40	Inflammatory bowel disease	7.000000e-42
GCST004861_35	Itch intensity from mosquito bite	2.000000e-08
GCST90002390_335	Mean corpuscular hemoglobin	2.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0004527	mean corpuscular hemoglobin

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2208 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

29 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 349,969 (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
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1173655	AFATINIB	4	15,144
CHEMBL1289601	LENVATINIB	4	8,784
CHEMBL1946170	REGORAFENIB	4	12,678
CHEMBL3301612	ENCORAFENIB	4	4,624
CHEMBL5416410	DASATINIB	4	655
CHEMBL1088752	LOSMAPIMOD	3	865
CHEMBL3544983	TESEVATINIB	3	2,819
CHEMBL603469	LESTAURTINIB	3
CHEMBL1090090	VX-702	2	1,045
CHEMBL1230165	SILMITASERTIB	2	593
CHEMBL14249	ADENOSINE TRIPHOSPHATE	2	287,353
CHEMBL1738757	REBASTINIB	2	1,478
CHEMBL1950289	TANZISERTIB	2	419
CHEMBL1980715	LAUROGUADINE	2	294
CHEMBL2029988	CEP-32496	2	1,136
CHEMBL206834	BAFETINIB	2	1,024
CHEMBL253969	OSI-632	2	1,150
CHEMBL3704901	ZUNSEMETINIB	2	191
CHEMBL3907479	FGFR INHIBITOR DEBIO 1347	2	762
CHEMBL3991932	PEXMETINIB	2
CHEMBL514201	TALMAPIMOD	2
CHEMBL5314585	GAMCEMETINIB	2
CHEMBL572878	TOZASERTIB	2
CHEMBL575448	BMS-754807	2
CHEMBL1090479	GSK-1070916	1
CHEMBL2140408	AMG-900	1
CHEMBL3545328	XL-019	1
CHEMBL3809901	MMI-0100	1

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — MAPKAPK subfamily

Most potent curated ligand interactions (7 total), top 7:

Ligand	Action	Affinity	Parameter
PF-3644022	Inhibition	8.28	pIC50
compound 16 [PMID: 17480064]	Inhibition	8.07	pIC50
compound 16 [PMID: 18945615]	Inhibition	7.29	pIC50
gamcemetinib	Irreversible inhibition	6.81	pIC50
compound 8 [PMID: 17480064]	Inhibition	6.77	pIC50
MK2a inhibitor	Inhibition	6.48	pKi
compound 33 [PMID: 19364658]	Inhibition	6.41	pIC50

Binding affinities (BindingDB)

173 measured of 285 human assays (285 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Staurosporine	KD	1.7 nM
Pyrrolopyridine, 33	IC50	8 nM
Pyrrolopyridine, 35	IC50	8 nM
Pyrrolopyridine, 16	IC50	8.5 nM
JMC502647 Compound 8	IC50	10 nM
carboline analog, 85	IC50	10 nM
Pyrrolopyridine, 32	IC50	15 nM
Pyrrolopyridine, 34	IC50	17 nM
carboline analog, 77	IC50	17 nM
3-chloro-4-[(3,5-difluoro-2-pyridinyl)methoxy]-1-[2-[2-(2-hydroxypropan-2-yl)pyrimidin-4-yl]-5-methyl-4-pyridinyl]-6-methylpyridin-2-one	IC50	21 nM	US-9115089: Methyl/fluoro-pyridinyl-methoxy substituted pyridinone-pyridinyl compounds and fluoro-pyrimidinyl-methoxy substituted pyridinone-pyridinyl compounds
Pyrrolopyridine, 19	IC50	21 nM
carboline analog, 80	IC50	21 nM
Pyrrolopyridine, 31	IC50	22 nM
Pyrrolopyridine, 18	IC50	25 nM
indole-based 7-membered lactam, 25a	IC50	29 nM
Pyrrolopyridine, 15	IC50	30 nM
Pyrrolopyridine, 24	IC50	30 nM
carboline analog, 81	IC50	31 nM
Pyrrolopyridine, 22	IC50	32 nM
carboline analog, 76	IC50	34 nM
carboline analog, 78	IC50	35 nM
indole-based 7-membered lactam, 25b	IC50	35 nM
Pyrrolopyridine, 21	IC50	37 nM
Pyrrolopyridine, 30	IC50	41 nM
Pyrrolo-pyrimidone, 15	IC50	42 nM
carboline analog, 83	IC50	44 nM
carboline analog, 82	IC50	45 nM
Pyrrolopyridine, 36	IC50	46 nM
Pyrrolopyridine, 11	IC50	48 nM
Pyrrolopyridine, 25	IC50	50 nM
Pyrrolopyridine, 28	IC50	51 nM
Pyrrolo-pyrimidone, 16	IC50	51 nM
Pyrrolopyridine, 14	IC50	52 nM
indole-based 7-membered lactam, 25c	IC50	52 nM
Pyrrolopyridine, 29	IC50	55 nM
Pyrrolopyridine, 10	IC50	56 nM
Pyrrolopyridine, 37	IC50	56 nM
Pyrrolopyridine, 27	IC50	62 nM
Pyrrolopyridine, 9	IC50	66 nM
Pyrrolopyridine, 26	IC50	71 nM
carboline analog, 74	IC50	72 nM
Pyrrolopyridine, 13	IC50	76 nM
Pyrrolo-pyrimidone, 17	IC50	82 nM
Pyrrolopyridine, 12	IC50	83 nM
carboline analog, 71	IC50	83 nM
carboline analog, 73	IC50	120 nM
1-[2-(2-tert-butylpyrimidin-4-yl)-5-methyl-4-pyridinyl]-3-chloro-4-[(2,4-difluorophenyl)methoxy]-6-methylpyridin-2-one	IC50	121 nM	US-9365546: Substituted pyridinone-pyridinyl compounds
carboline analog, 79	IC50	124 nM
Pyrrolopyridine, 23	IC50	126 nM
3-chloro-4-[(2,4-difluorophenyl)methoxy]-1-[2-[2-(2-hydroxypropan-2-yl)pyrimidin-4-yl]-5-methyl-4-pyridinyl]-6-methylpyridin-2-one	IC50	138 nM	US-9365546: Substituted pyridinone-pyridinyl compounds

ChEMBL bioactivities

1221 potent at pChembl≥5 of 1364 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.52	Kd	0.3	nM	VX-702
9.21	EC50	0.62	nM	CHEMBL1933189
9.15	EC50	0.71	nM	CHEMBL1933188
9.14	EC50	0.72	nM	CHEMBL1933164
9.02	EC50	0.96	nM	CHEMBL1933166
9.00	IC50	1	nM	CHEMBL5613264
9.00	IC50	1	nM	CHEMBL5612036
9.00	IC50	1	nM	CHEMBL561334
9.00	IC50	1	nM	CHEMBL1801384
9.00	EC50	1	nM	CHEMBL1933162
8.96	EC50	1.1	nM	CHEMBL1779362
8.96	EC50	1.1	nM	CHEMBL1933171
8.89	EC50	1.3	nM	CHEMBL1933190
8.85	EC50	1.4	nM	CHEMBL1933176
8.82	EC50	1.5	nM	CHEMBL1933173
8.80	EC50	1.6	nM	CHEMBL1933192
8.80	EC50	1.6	nM	CHEMBL1933175
8.80	EC50	1.6	nM	CHEMBL1933168
8.77	EC50	1.7	nM	CHEMBL1779367
8.72	IC50	1.9	nM	CHEMBL2385548
8.72	EC50	1.9	nM	CHEMBL1933191
8.70	IC50	2	nM	CHEMBL257834
8.70	IC50	2	nM	CHEMBL403154
8.70	IC50	2	nM	CHEMBL258045
8.70	IC50	2	nM	CHEMBL1231206
8.70	IC50	2	nM	CHEMBL5613453
8.70	IC50	2	nM	CHEMBL556392
8.68	EC50	2.1	nM	CHEMBL1779366
8.64	EC50	2.3	nM	CHEMBL1933169
8.62	EC50	2.4	nM	CHEMBL1933181
8.60	EC50	2.5	nM	CHEMBL1933186
8.60	EC50	2.5	nM	CHEMBL1933179
8.60	EC50	2.5	nM	CHEMBL1933172
8.59	EC50	2.6	nM	CHEMBL1933177
8.59	EC50	2.6	nM	CHEMBL1933170
8.57	EC50	2.7	nM	CHEMBL1933174
8.54	IC50	2.9	nM	CHEMBL1938685
8.52	IC50	3	nM	CHEMBL2385549
8.52	IC50	3	nM	CHEMBL403258
8.52	IC50	3	nM	CHEMBL256194
8.52	IC50	3	nM	CHEMBL5613230
8.52	Ki	3	nM	CHEMBL1231206
8.51	EC50	3.1	nM	CHEMBL1933161
8.50	Ki	3.162	nM	CHEMBL592030
8.48	EC50	3.3	nM	CHEMBL1933187
8.44	EC50	3.6	nM	CHEMBL1779365
8.42	IC50	3.8	nM	CHEMBL1938687
8.40	IC50	4	nM	CHEMBL255991
8.40	IC50	4	nM	CHEMBL5612647
8.40	IC50	4	nM	CHEMBL5613911

PubChem BioAssay actives

1125 with measured affinity, of 4134 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-(N-carbamoyl-2,6-difluoroanilino)-2-(2,4-difluorophenyl)pyridine-3-carboxamide	1425065: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0003	uM
N-[4-(4-oxospiro[5,6-dihydro-1H-pyrrolo[3,2-c]pyridine-7,3’-pyrrolidine]-2-yl)-2-pyridinyl]naphthalene-2-carboxamide	637912: Inhibition of MK2 using Fluo-betaA-11A NeoMPS as substrate pre-incubated for 30 mins before substrate addition measured after 2 hrs by IMAP assay	ec50	0.0006	uM
N-[4-(4-oxospiro[5,6-dihydro-1H-pyrrolo[3,2-c]pyridine-7,4’-piperidine]-2-yl)-2-pyridinyl]naphthalene-2-carboxamide	637912: Inhibition of MK2 using Fluo-betaA-11A NeoMPS as substrate pre-incubated for 30 mins before substrate addition measured after 2 hrs by IMAP assay	ec50	0.0007	uM
3,4-dimethyl-N-[4-(4-oxospiro[5,6-dihydro-1H-pyrrolo[3,2-c]pyridine-7,3’-pyrrolidine]-2-yl)-2-pyridinyl]benzamide	637912: Inhibition of MK2 using Fluo-betaA-11A NeoMPS as substrate pre-incubated for 30 mins before substrate addition measured after 2 hrs by IMAP assay	ec50	0.0007	uM
4-[(E)-2-[4-(morpholin-4-ylmethyl)phenyl]ethenyl]-5,13,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1,3,6,8,10,16-hexaen-12-one	604988: Inhibition of human MK2 using hsp27 peptide biotinyl-AYSRALSRQLSSGVSEIRCOOH as substrate after 45 mins by FRET assay	ic50	0.0010	uM
(15S)-5-(2-ethenylimidazol-1-yl)-15-(fluoromethyl)-11-thia-6,14,17-triazatetracyclo[8.8.0.02,7.012,18]octadeca-1(10),2(7),3,5,8,12(18)-hexaen-13-one	2127431: Inhibition of MK2 (unknown origin) using ST3-Sox peptide as substrate measured for 120 mins in presence of ATP by Synergy H4 plate reader analysis	ic50	0.0010	uM
(15R)-5-[6-ethenyl-2-(methoxymethyl)pyrimidin-4-yl]-15-methyl-11-thia-6,14,17-triazatetracyclo[8.8.0.02,7.012,18]octadeca-1(10),2(7),3,5,8,12(18)-hexaen-13-one	2127431: Inhibition of MK2 (unknown origin) using ST3-Sox peptide as substrate measured for 120 mins in presence of ATP by Synergy H4 plate reader analysis	ic50	0.0010	uM
(15R)-15-methyl-11-thia-6,14,17-triazatetracyclo[8.8.0.02,7.012,18]octadeca-1(10),2(7),3,5,8,12(18)-hexaen-13-one	430427: Inhibition of MK2	ic50	0.0010	uM
3,4-dimethyl-N-[4-(4-oxospiro[5,6-dihydro-1H-pyrrolo[3,2-c]pyridine-7,4’-piperidine]-2-yl)-2-pyridinyl]benzamide	637912: Inhibition of MK2 using Fluo-betaA-11A NeoMPS as substrate pre-incubated for 30 mins before substrate addition measured after 2 hrs by IMAP assay	ec50	0.0010	uM
N-[4-(4-oxospiro[5,6-dihydro-1H-pyrrolo[3,2-c]pyridine-7,4’-piperidine]-2-yl)-2-pyridinyl]naphthalene-1-carboxamide	637912: Inhibition of MK2 using Fluo-betaA-11A NeoMPS as substrate pre-incubated for 30 mins before substrate addition measured after 2 hrs by IMAP assay	ec50	0.0010	uM
2-(2-pyridin-3-ylpyrimidin-4-yl)spiro[5,6-dihydro-1H-pyrrolo[3,2-c]pyridine-7,4’-piperidine]-4-one	598897: Inhibition of MK2 pretreated for 30 mins before fluorescein labeled substrate peptide addition measured after 2 hrs by IMAP assay	ec50	0.0011	uM
3-fluoro-N-[4-(4-oxospiro[5,6-dihydro-1H-pyrrolo[3,2-c]pyridine-7,4’-piperidine]-2-yl)-2-pyridinyl]benzamide	637912: Inhibition of MK2 using Fluo-betaA-11A NeoMPS as substrate pre-incubated for 30 mins before substrate addition measured after 2 hrs by IMAP assay	ec50	0.0011	uM
4-fluoro-N-[4-(4-oxospiro[5,6-dihydro-1H-pyrrolo[3,2-c]pyridine-7,3’-pyrrolidine]-2-yl)-2-pyridinyl]benzamide	637912: Inhibition of MK2 using Fluo-betaA-11A NeoMPS as substrate pre-incubated for 30 mins before substrate addition measured after 2 hrs by IMAP assay	ec50	0.0013	uM
N-[4-(4-oxospiro[5,6-dihydro-1H-pyrrolo[3,2-c]pyridine-7,4’-piperidine]-2-yl)-2-pyridinyl]pyridine-2-carboxamide	637912: Inhibition of MK2 using Fluo-betaA-11A NeoMPS as substrate pre-incubated for 30 mins before substrate addition measured after 2 hrs by IMAP assay	ec50	0.0014	uM
N-[4-(4-oxospiro[5,6-dihydro-1H-pyrrolo[3,2-c]pyridine-7,4’-piperidine]-2-yl)-2-pyridinyl]-3-(trifluoromethoxy)benzamide	637912: Inhibition of MK2 using Fluo-betaA-11A NeoMPS as substrate pre-incubated for 30 mins before substrate addition measured after 2 hrs by IMAP assay	ec50	0.0015	uM
4-fluoro-N-[4-(4-oxospiro[5,6-dihydro-1H-pyrrolo[3,2-c]pyridine-7,4’-piperidine]-2-yl)-2-pyridinyl]benzamide	637912: Inhibition of MK2 using Fluo-betaA-11A NeoMPS as substrate pre-incubated for 30 mins before substrate addition measured after 2 hrs by IMAP assay	ec50	0.0016	uM
N-[4-(4-oxospiro[5,6-dihydro-1H-pyrrolo[3,2-c]pyridine-7,3’-pyrrolidine]-2-yl)-2-pyridinyl]-3-(trifluoromethoxy)benzamide	637912: Inhibition of MK2 using Fluo-betaA-11A NeoMPS as substrate pre-incubated for 30 mins before substrate addition measured after 2 hrs by IMAP assay	ec50	0.0016	uM
N-[4-(4-oxospiro[5,6-dihydro-1H-pyrrolo[3,2-c]pyridine-7,4’-piperidine]-2-yl)-2-pyridinyl]-4-(trifluoromethyl)benzamide	637912: Inhibition of MK2 using Fluo-betaA-11A NeoMPS as substrate pre-incubated for 30 mins before substrate addition measured after 2 hrs by IMAP assay	ec50	0.0016	uM
2-[2-[2-(cyclopentylamino)pyrimidin-5-yl]pyrimidin-4-yl]spiro[5,6-dihydro-1H-pyrrolo[3,2-c]pyridine-7,4’-piperidine]-4-one	598897: Inhibition of MK2 pretreated for 30 mins before fluorescein labeled substrate peptide addition measured after 2 hrs by IMAP assay	ec50	0.0017	uM
4-[4-oxo-8-piperazin-1-yl-5-[(2-pyrimidin-5-ylphenyl)methyl]-10H-furo[2,3-c][1]benzazepin-2-yl]benzonitrile	749353: Inhibition of MK2 (unknown origin) phosphorylation using TAMRA labeled peptide as substrate incubated 30 mins before substrate addition measured after 30 mins	ic50	0.0019	uM
3-fluoro-N-[4-(4-oxospiro[5,6-dihydro-1H-pyrrolo[3,2-c]pyridine-7,3’-pyrrolidine]-2-yl)-2-pyridinyl]benzamide	637912: Inhibition of MK2 using Fluo-betaA-11A NeoMPS as substrate pre-incubated for 30 mins before substrate addition measured after 2 hrs by IMAP assay	ec50	0.0019	uM
(15R)-15-methyl-5-[6-(3-morpholin-4-ylprop-1-en-2-yl)pyrimidin-4-yl]-11-thia-6,14,17-triazatetracyclo[8.8.0.02,7.012,18]octadeca-1(10),2(7),3,5,8,12(18)-hexaen-13-one	2127431: Inhibition of MK2 (unknown origin) using ST3-Sox peptide as substrate measured for 120 mins in presence of ATP by Synergy H4 plate reader analysis	ic50	0.0020	uM
N-[1-(2,2-dimethylpropyl)piperidin-4-yl]-2-[(1-oxospiro[2,3-dihydropyrazino[1,2-a]indole-4,1’-cyclobutane]-7-carbonyl)amino]-1,3-thiazole-4-carboxamide	1894050: Inhibition of human MK2	ic50	0.0020	uM
2-[(4,4-dimethyl-1-oxo-2,3-dihydropyrazino[1,2-a]indole-7-carbonyl)amino]-N-[1-(2,2-dimethylpropyl)piperidin-4-yl]-1,3-thiazole-4-carboxamide	321805: Inhibition of MK2	ic50	0.0020	uM
N-(1-methylpiperidin-4-yl)-2-[(1-oxospiro[2,3-dihydropyrazino[1,2-a]indole-4,1’-cyclobutane]-7-carbonyl)amino]-1,3-thiazole-4-carboxamide	321805: Inhibition of MK2	ic50	0.0020	uM
(15R)-15-methyl-5-(6-methyl-3-pyridinyl)-11-thia-6,14,17-triazatetracyclo[8.8.0.02,7.012,18]octadeca-1(10),2(7),3,5,8,12(18)-hexaen-13-one	1894050: Inhibition of human MK2	ic50	0.0020	uM
(15R)-5-chloro-15-methyl-11-thia-6,14,17-triazatetracyclo[8.8.0.02,7.012,18]octadeca-1(10),2(7),3,5,8,12(18)-hexaen-13-one	430427: Inhibition of MK2	ic50	0.0020	uM
2-[2-(2-aminopyrimidin-5-yl)pyrimidin-4-yl]spiro[5,6-dihydro-1H-pyrrolo[3,2-c]pyridine-7,4’-piperidine]-4-one	598897: Inhibition of MK2 pretreated for 30 mins before fluorescein labeled substrate peptide addition measured after 2 hrs by IMAP assay	ec50	0.0021	uM
3,4-dimethyl-N-[4-(1’-methyl-4-oxospiro[5,6-dihydro-1H-pyrrolo[3,2-c]pyridine-7,4’-piperidine]-2-yl)-2-pyridinyl]benzamide	637912: Inhibition of MK2 using Fluo-betaA-11A NeoMPS as substrate pre-incubated for 30 mins before substrate addition measured after 2 hrs by IMAP assay	ec50	0.0023	uM
4-fluoro-N-[4-(4-oxospiro[5,6-dihydro-1H-pyrrolo[3,2-c]pyridine-7,3’-piperidine]-2-yl)-2-pyridinyl]benzamide	637912: Inhibition of MK2 using Fluo-betaA-11A NeoMPS as substrate pre-incubated for 30 mins before substrate addition measured after 2 hrs by IMAP assay	ec50	0.0024	uM
3-fluoro-N-[4-(1’-methyl-4-oxospiro[5,6-dihydro-1H-pyrrolo[3,2-c]pyridine-7,4’-piperidine]-2-yl)-2-pyridinyl]benzamide	637912: Inhibition of MK2 using Fluo-betaA-11A NeoMPS as substrate pre-incubated for 30 mins before substrate addition measured after 2 hrs by IMAP assay	ec50	0.0025	uM
3,5-difluoro-N-[4-(4-oxospiro[5,6-dihydro-1H-pyrrolo[3,2-c]pyridine-7,3’-piperidine]-2-yl)-2-pyridinyl]benzamide	637912: Inhibition of MK2 using Fluo-betaA-11A NeoMPS as substrate pre-incubated for 30 mins before substrate addition measured after 2 hrs by IMAP assay	ec50	0.0025	uM
N-[4-(4-oxospiro[5,6-dihydro-1H-pyrrolo[3,2-c]pyridine-7,3’-piperidine]-2-yl)-2-pyridinyl]naphthalene-2-carboxamide	637912: Inhibition of MK2 using Fluo-betaA-11A NeoMPS as substrate pre-incubated for 30 mins before substrate addition measured after 2 hrs by IMAP assay	ec50	0.0025	uM
N-[4-(1’-methyl-4-oxospiro[5,6-dihydro-1H-pyrrolo[3,2-c]pyridine-7,4’-piperidine]-2-yl)-2-pyridinyl]naphthalene-2-carboxamide	637912: Inhibition of MK2 using Fluo-betaA-11A NeoMPS as substrate pre-incubated for 30 mins before substrate addition measured after 2 hrs by IMAP assay	ec50	0.0026	uM
N-[4-(4-oxospiro[5,6-dihydro-1H-pyrrolo[3,2-c]pyridine-7,4’-piperidine]-2-yl)-2-pyridinyl]pyridine-4-carboxamide	637912: Inhibition of MK2 using Fluo-betaA-11A NeoMPS as substrate pre-incubated for 30 mins before substrate addition measured after 2 hrs by IMAP assay	ec50	0.0026	uM
N-[4-(1’-methyl-4-oxospiro[5,6-dihydro-1H-pyrrolo[3,2-c]pyridine-7,4’-piperidine]-2-yl)-2-pyridinyl]-3-(trifluoromethoxy)benzamide	637912: Inhibition of MK2 using Fluo-betaA-11A NeoMPS as substrate pre-incubated for 30 mins before substrate addition measured after 2 hrs by IMAP assay	ec50	0.0027	uM
4-(15-piperazin-1-yl-8-oxa-2,5-diazatetracyclo[11.4.0.02,6.07,11]heptadeca-1(13),3,5,7(11),9,14,16-heptaen-9-yl)benzonitrile	640489: Inhibition of MK2 using TAMRA-labeled peptide as substrate pre-incubated for 30 mins prior substrate addition measured after 30 mins incubation in dark using fluorescence polarization assay	ic50	0.0029	uM
3-fluoro-4-(3-fluorophenyl)-1’-methylspiro[5,13,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(10),2,4,6,11(16)-pentaene-15,3’-azetidine]-12-one	1410522: Inhibition of human MK2 using hsp27 peptide biotinyl-AYSRALSRQLSSGVSEIRCOOH as substrate after 45 mins by TR-FRET assay	ic50	0.0030	uM
3-fluoro-4-(3-fluoro-4-methoxyphenyl)-1’-methylspiro[5,13,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(10),2,4,6,11(16)-pentaene-15,3’-azetidine]-12-one	1410522: Inhibition of human MK2 using hsp27 peptide biotinyl-AYSRALSRQLSSGVSEIRCOOH as substrate after 45 mins by TR-FRET assay	ic50	0.0030	uM
3-fluoro-4-(6-methoxy-3-pyridinyl)-1’-methylspiro[5,13,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(10),2,4,6,11(16)-pentaene-15,3’-azetidine]-12-one	1410522: Inhibition of human MK2 using hsp27 peptide biotinyl-AYSRALSRQLSSGVSEIRCOOH as substrate after 45 mins by TR-FRET assay	ic50	0.0030	uM
(15R)-5-[6-ethynyl-2-(4-methylpiperazin-1-yl)pyrimidin-4-yl]-15-methyl-11-thia-6,14,17-triazatetracyclo[8.8.0.02,7.012,18]octadeca-1(10),2(7),3,5,8,12(18)-hexaen-13-one	2127431: Inhibition of MK2 (unknown origin) using ST3-Sox peptide as substrate measured for 120 mins in presence of ATP by Synergy H4 plate reader analysis	ic50	0.0030	uM
4-(2-fluorophenyl)-1’-methylspiro[5,13,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(10),2,4,6,11(16)-pentaene-15,3’-azetidine]-12-one	604890: Inhibition of human MK2 using biotinyl-AYSRALSRQLSSGVSEIRCOOH as substrate after 45 mins by FRET analysis	ic50	0.0030	uM
4-(4-methoxyphenyl)-1’-methylspiro[3,5,13,17-tetrazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(10),2,4,6,11(16)-pentaene-15,3’-azetidine]-12-one	604890: Inhibition of human MK2 using biotinyl-AYSRALSRQLSSGVSEIRCOOH as substrate after 45 mins by FRET analysis	ic50	0.0030	uM
N-(1-benzylpiperidin-4-yl)-2-[(1-oxospiro[2,3-dihydropyrazino[1,2-a]indole-4,1’-cyclobutane]-7-carbonyl)amino]-1,3-thiazole-4-carboxamide	321805: Inhibition of MK2	ic50	0.0030	uM
N-[1-(2,2-dimethylpropyl)piperidin-4-yl]-2-[(4-methyl-1-oxo-3,4-dihydro-2H-pyrazino[1,2-a]indole-7-carbonyl)amino]-1,3-thiazole-4-carboxamide	321805: Inhibition of MK2	ic50	0.0030	uM
4-(6-fluoro-3-pyridinyl)-1’-methylspiro[5,13,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(10),2,4,6,11(16)-pentaene-15,3’-azetidine]-12-one	604890: Inhibition of human MK2 using biotinyl-AYSRALSRQLSSGVSEIRCOOH as substrate after 45 mins by FRET analysis	ic50	0.0030	uM
1’-methyl-4-[4-(2-morpholin-4-ylethoxy)phenyl]spiro[3,5,13,17-tetrazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(10),2,4,6,11(16)-pentaene-15,3’-azetidine]-12-one	604890: Inhibition of human MK2 using biotinyl-AYSRALSRQLSSGVSEIRCOOH as substrate after 45 mins by FRET analysis	ic50	0.0030	uM
4-[5-(3-methoxypropoxy)-3-pyridinyl]-1’-methylspiro[5,13,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(10),2,4,6,11(16)-pentaene-15,3’-azetidine]-12-one	604890: Inhibition of human MK2 using biotinyl-AYSRALSRQLSSGVSEIRCOOH as substrate after 45 mins by FRET analysis	ic50	0.0030	uM
4-(3-fluorophenyl)-1’-methylspiro[5,13,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(10),2,4,6,11(16)-pentaene-15,3’-azetidine]-12-one	604890: Inhibition of human MK2 using biotinyl-AYSRALSRQLSSGVSEIRCOOH as substrate after 45 mins by FRET analysis	ic50	0.0030	uM
1’-ethyl-4-(2-fluorophenyl)spiro[5,13,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(10),2,4,6,11(16)-pentaene-15,3’-azetidine]-12-one	604890: Inhibition of human MK2 using biotinyl-AYSRALSRQLSSGVSEIRCOOH as substrate after 45 mins by FRET analysis	ic50	0.0030	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
SB 203580	decreases reaction, increases activity, increases phosphorylation, increases expression, decreases phosphorylation	12
sodium arsenite	increases activity, increases phosphorylation, increases expression, decreases reaction	4
Tretinoin	decreases reaction, increases phosphorylation, increases expression	3
Arsenic Trioxide	decreases expression, increases activity, decreases reaction	2
Acetaminophen	decreases expression, increases expression	2
Benzene	decreases expression, increases expression	2
Lipopolysaccharides	increases activity, increases phosphorylation, increases reaction, decreases reaction	2
Ozone	increases phosphorylation, decreases reaction, affects cotreatment, increases expression	2
Sorbitol	increases activity, decreases reaction, increases phosphorylation	2
GSK-J4	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
geldanamycin	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
trichostatin A	decreases expression	1
arsenite	increases activity, decreases reaction	1
sodium bichromate	decreases expression	1
nickel subsulfide	decreases expression	1
nickel sulfate	increases phosphorylation, affects cotreatment	1
tamibarotene	increases expression	1
KN 62	decreases activity	1
coniferaldehyde	affects localization, decreases reaction, increases phosphorylation, increases expression	1
rottlerin	decreases activity	1
CGP 52608	affects binding, increases reaction	1
LY 303511	increases phosphorylation, decreases reaction	1
3-(4-methylphenylsulfonyl)-2-propenenitrile	increases activity, increases phosphorylation, increases reaction	1
SCIO-469	decreases activity	1
picoxystrobin	decreases expression	1
ralimetinib	decreases reaction, increases phosphorylation	1

ChEMBL screening assays

758 unique, capped per target: 746 binding, 11 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000373	Binding	Inhibition of MAPK2/ERK2 at 10 uM	Synthesis and structure-activity relationships of N-6 substituted analogues of 9-hydroxy-4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones as inhibitors of Wee1 and Chk1 checkpoint kinases. — Eur J Med Chem
CHEMBL1963729	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: MAPKAPK2	PubChem BioAssay data set
CHEMBL4407584	ADMET	Inhibition of recombinant human full-length His-tagged MAPKAPK2 expressed in Escherichia coli at 25 uM using FRET-labeled Ser/Thr 04 peptide as substrate measured after 1 hr by Z’-lyte assay relative to control	Optimization and Mechanistic Characterization of Pyridopyrimidine Inhibitors of Bacterial Biotin Carboxylase. — J Med Chem

Cellosaurus cell lines

7 cell lines: 7 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1XI	Abcam A-549 MAPKAPK2 KO	Cancer cell line	Male
CVCL_D2BS	Abcam HCT 116 MAPKAPK2 KO	Cancer cell line	Male
CVCL_D8QA	Ubigene HCT 116 MAPKAPK2 KO	Cancer cell line	Male
CVCL_E0HK	Ubigene HeLa MAPKAPK2 KO	Cancer cell line	Female
CVCL_F1R4	HyCyte JEG-3 KO-hMAPKAPK2	Cancer cell line	Male
CVCL_SX04	HAP1 MAPKAPK2 (-) 1	Cancer cell line	Male
CVCL_SX05	HAP1 MAPKAPK2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
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