MAPK10

Summary

MAPK10 (mitogen-activated protein kinase 10, HGNC:6872) is a protein-coding gene on chromosome 4q21.3, encoding Mitogen-activated protein kinase 10 (P53779). Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration and programmed cell death.

The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as integration points for multiple biochemical signals, and thus are involved in a wide variety of cellular processes, such as proliferation, differentiation, transcription regulation and development. This kinase is specifically expressed in a subset of neurons in the nervous system, and is activated by threonine and tyrosine phosphorylation. Targeted deletion of this gene in mice suggests that it may have a role in stress-induced neuronal apoptosis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. A recent study provided evidence for translational readthrough in this gene, and expression of an additional C-terminally extended isoform via the use of an alternative in-frame translation termination codon.

Source: NCBI Gene 5602 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Lennox-Gastaut syndrome (Limited, GenCC)
• GWAS associations: 11
• Clinical variants (ClinVar): 54 total
• Phenotypes (HPO): 25
• Druggable target: yes — 58 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_138982

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6872
Approved symbol	MAPK10
Name	mitogen-activated protein kinase 10
Location	4q21.3
Locus type	gene with protein product
Status	Approved
Aliases	JNK3, p493F12, p54bSAPK
Ensembl gene	ENSG00000109339
Ensembl biotype	protein_coding
OMIM	602897
Entrez	5602

Gene structure

Transcript identifiers

Ensembl transcripts: 195 — 119 protein_coding, 35 nonsense_mediated_decay, 24 protein_coding_CDS_not_defined, 17 retained_intron

ENST00000310816, ENST00000359221, ENST00000361569, ENST00000395157, ENST00000395160, ENST00000395166, ENST00000395169, ENST00000430389, ENST00000449047, ENST00000472236, ENST00000475679, ENST00000479377, ENST00000486985, ENST00000489368, ENST00000502302, ENST00000503911, ENST00000504397, ENST00000505356, ENST00000506773, ENST00000508262, ENST00000509464, ENST00000511167, ENST00000511328, ENST00000512017, ENST00000512046, ENST00000512564, ENST00000512689, ENST00000513186, ENST00000513839, ENST00000514856, ENST00000515400, ENST00000515650, ENST00000564854, ENST00000638225, ENST00000638313, ENST00000638499, ENST00000638867, ENST00000638946, ENST00000639175, ENST00000639234, ENST00000639242, ENST00000639930, ENST00000639972, ENST00000639989, ENST00000640064, ENST00000640445, ENST00000640490, ENST00000640527, ENST00000640544, ENST00000640858, ENST00000640970, ENST00000641010, ENST00000641016, ENST00000641020, ENST00000641022, ENST00000641032, ENST00000641037, ENST00000641041, ENST00000641047, ENST00000641050, ENST00000641051, ENST00000641052, ENST00000641058, ENST00000641061, ENST00000641066, ENST00000641072, ENST00000641080, ENST00000641101, ENST00000641102, ENST00000641108, ENST00000641110, ENST00000641116, ENST00000641120, ENST00000641126, ENST00000641130, ENST00000641142, ENST00000641148, ENST00000641157, ENST00000641166, ENST00000641170, ENST00000641184, ENST00000641195, ENST00000641203, ENST00000641207, ENST00000641208, ENST00000641217, ENST00000641221, ENST00000641227, ENST00000641237, ENST00000641253, ENST00000641255, ENST00000641265, ENST00000641273, ENST00000641274, ENST00000641283, ENST00000641287, ENST00000641297, ENST00000641300, ENST00000641306, ENST00000641313, ENST00000641317, ENST00000641324, ENST00000641341, ENST00000641345, ENST00000641347, ENST00000641358, ENST00000641372, ENST00000641379, ENST00000641384, ENST00000641385, ENST00000641391, ENST00000641405, ENST00000641408, ENST00000641410, ENST00000641430, ENST00000641435, ENST00000641452, ENST00000641459, ENST00000641462, ENST00000641467, ENST00000641485, ENST00000641493, ENST00000641531, ENST00000641537, ENST00000641543, ENST00000641550, ENST00000641553, ENST00000641555, ENST00000641561, ENST00000641563, ENST00000641595, ENST00000641607, ENST00000641609, ENST00000641620, ENST00000641629, ENST00000641634, ENST00000641647, ENST00000641653, ENST00000641656, ENST00000641657, ENST00000641675, ENST00000641677, ENST00000641718, ENST00000641724, ENST00000641737, ENST00000641762, ENST00000641763, ENST00000641767, ENST00000641777, ENST00000641782, ENST00000641798, ENST00000641803, ENST00000641823, ENST00000641824, ENST00000641826, ENST00000641831, ENST00000641854, ENST00000641855, ENST00000641858, ENST00000641862, ENST00000641864, ENST00000641873, ENST00000641881, ENST00000641902, ENST00000641903, ENST00000641907, ENST00000641911, ENST00000641917, ENST00000641943, ENST00000641952, ENST00000641954, ENST00000641983, ENST00000641985, ENST00000641989, ENST00000641997, ENST00000642006, ENST00000642009, ENST00000642013, ENST00000642015, ENST00000642019, ENST00000642023, ENST00000642032, ENST00000642033, ENST00000642035, ENST00000642038, ENST00000642048, ENST00000642049, ENST00000642060, ENST00000642081, ENST00000642098, ENST00000642103, ENST00000642136, ENST00000885434, ENST00000950511, ENST00000950512

RefSeq mRNA: 9 — MANE Select: NM_138982 NM_001318067, NM_001318068, NM_001318069, NM_001351624, NM_001351625, NM_001363657, NM_002753, NM_138980, NM_138982

CCDS: CCDS34026, CCDS3612, CCDS43247, CCDS87241, CCDS87242, CCDS87243, CCDS93556

Canonical transcript exons

ENST00000641462 — 14 exons

Exon	Start	End
ENSE00001352600	86354530	86354644
ENSE00002433828	86098524	86098595
ENSE00003470811	86194336	86194407
ENSE00003503801	86029197	86029274
ENSE00003518397	86103186	86103244
ENSE00003523984	86101894	86102032
ENSE00003535929	86064266	86064390
ENSE00003562222	86067773	86067955
ENSE00003598073	86101052	86101217
ENSE00003615544	86159298	86159467
ENSE00003648739	86031368	86031431
ENSE00003786679	86107223	86107352
ENSE00003806022	86359658	86360053
ENSE00003812161	86010405	86017370

Expression profiles

Bgee: expression breadth ubiquitous, 217 present calls, max score 97.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.3525 / max 1593.2512, expressed in 929 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52973	13.5236	369
52976	2.7361	347
52981	2.3647	617
52972	2.1324	229
52974	0.6155	155
52980	0.3474	159
52978	0.1582	86
52971	0.1074	48
52969	0.0775	44
52975	0.0589	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	97.96	gold quality
prefrontal cortex	UBERON:0000451	97.46	gold quality
right frontal lobe	UBERON:0002810	97.33	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.21	gold quality
primary visual cortex	UBERON:0002436	96.89	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.88	gold quality
middle temporal gyrus	UBERON:0002771	96.54	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.46	gold quality
cingulate cortex	UBERON:0003027	96.31	gold quality
frontal cortex	UBERON:0001870	96.25	gold quality
anterior cingulate cortex	UBERON:0009835	96.25	gold quality
frontal lobe	UBERON:0016525	96.25	gold quality
neocortex	UBERON:0001950	96.07	gold quality
endothelial cell	CL:0000115	95.87	gold quality
frontal pole	UBERON:0002795	95.86	gold quality
right uterine tube	UBERON:0001302	95.31	gold quality
cerebral cortex	UBERON:0000956	95.30	gold quality
superior frontal gyrus	UBERON:0002661	95.14	gold quality
amygdala	UBERON:0001876	94.93	gold quality
caudate nucleus	UBERON:0001873	94.87	gold quality
occipital lobe	UBERON:0002021	94.87	gold quality
telencephalon	UBERON:0001893	94.73	gold quality
Brodmann (1909) area 10	UBERON:0013541	94.69	gold quality
nucleus accumbens	UBERON:0001882	94.60	gold quality
postcentral gyrus	UBERON:0002581	94.58	gold quality
adenohypophysis	UBERON:0002196	94.36	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.34	gold quality
forebrain	UBERON:0001890	94.18	gold quality
parietal lobe	UBERON:0001872	93.92	gold quality
putamen	UBERON:0001874	93.68	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-CURD-6	yes	3670.85
E-MTAB-10018	yes	318.59
E-MTAB-7037	yes	161.94
E-HCAD-35	yes	62.72
E-CURD-119	yes	23.03
E-GEOD-81547	yes	20.41
E-ANND-3	yes	14.37
E-HCAD-5	yes	10.22
E-GEOD-137537	yes	7.72
E-ENAD-17	no	1042.91
E-MTAB-10137	no	534.86
E-GEOD-86618	no	126.88

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

228 targeting MAPK10, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3658	99.96	73.87	4379

Literature-anchored findings (GeneRIF, showing 31)

• Shares a promoter region with the tightly linked gene encoding Fas-associated phosphatase-1. (PMID:12436199)
• interaction of free arrestins with JNK3 and Mdm2 and their ability to regulate subcellular localization of these proteins may play an important role in the survival of photoreceptors and other neurons (PMID:16737965)
• Arrestin in all conformations binds JNK3 comparably, whereas Mdm2 preferentially binds cone arrestin ‘frozen’ in the basal state. (PMID:17680991)
• JNK3 recruits MKK4 to the beta-arrestin-2 scaffold complex by binding to the MAPK docking domain (D-domain) located within the N terminus of MKK4. (PMID:18408005)
• the molecular interactions of arrestin2 and arrestin3 and their individual domains with the components of the two MAPK cascades, ASK1-MKK4-JNK3 and c-Raf-1-MEK1-ERK2 (PMID:19001375)
• JNK1, JNK2, and JNK3 are involved in P-glycoprotein-mediated multidrug resistance of hepatocellular carcinoma cells. (PMID:20525557)
• The results suggest the possible involvement of CaMKII and JNK3 in soman-induced long-term neurotoxicity. (PMID:21041242)
• results suggest that MAPK10 may have a proapoptotic function and could function as a tumor-suppressor gene in chromophobe renal cell carcinoma (PMID:21166945)
• [review] This review focuses on delineating the role of scaffold proteins, especially that of JNK3 as a target, on the regulation of JNK signaling in neurons. (PMID:21321401)
• Arrestin-3 acts as a “true” scaffold, facilitating JNK3alpha2 phosphorylation by bringing it and MAP kinase kinase (MKK)4 together. (PMID:22047447)
• Silent scaffolds: inhibition OF c-Jun N-terminal kinase 3 activity in cell by dominant-negative arrestin-3 mutant. (PMID:22523077)
• Subtle structural mechanisms for allosteric signaling between the peptide-binding site and activation loop of human JNK3. (PMID:23142346)
• reduced JNK3 activity has potentially deleterious effects on neuronal function via altered regulation of a set of post-synaptic proteins. (PMID:23329067)
• Mitogen-activated protein kinase 10 JNK3 alpha (JNK3apha2)binds to both domains of arrestin-3. (PMID:24412749)
• miR-29b mRNA, MAPK10 protein expression, and ATG9A protein expression are closely related to chemosensitivity of ovarian carcinoma. (PMID:24767251)
• JNK3 is required for the antiapoptotic effects of exendin 4 (PMID:25025079)
• analysis of the unique mechanisms by which JNK1beta1 is regulated (PMID:25178256)
• Study found that JNK3 levels are increased in brain tissue and CSF from patients with Alzheimer disease and CSF levels could reflect the rate of cognitive decline (PMID:25455349)
• Data indicate that tetra-substituted pyridinylimidazoles were designed as dual inhibitors of c-Jun N-terminal kinase (JNK) 3 and p38alpha mitogen-activated protein (MAP) kinase, and both kinases may be involved in the progression of Huntington’s disease. (PMID:25475894)
• Peptide mini-scaffold facilitates JNK3 activation in cells. (PMID:26868142)
• Mapk10 expression was regulated by miR27a-3p in nasopharyngeal carcinoma.Mapk10 gene was down-regulated in the nasopharyngeal carcinoma cells. (PMID:28393229)
• phosphorylation rate of JNK3 at Thr-221 by MKK7 is two orders of magnitude faster than the corresponding phosphorylation of Tyr-223 by MKK4 with or without arrestin-3 (PMID:30591558)
• Structural mechanisms of the arrestin-3/JNK3 interactions have been reported. (PMID:31080119)
• the present study identified a novel significant association between the increased expression levels of MAPK10, TUBB2B and RASL11B, and neuroblastoma cells. (PMID:31432180)
• Identification and neuroprotective evaluation of a potential c-Jun N-terminal kinase 3 inhibitor through structure-based virtual screening and in-vitro assay. (PMID:32040807)
• MicroRNA-4516-mediated regulation of MAPK10 relies on 3’ UTR cis-acting variants and contributes to the altered risk of Hirschsprung disease. (PMID:32066630)
• Propofol suppresses the progression of nonsmall cell lung cancer via downregulation of the miR215p/MAPK10 axis. (PMID:32468043)
• Circ_0000515 drives the progression of hepatocellular carcinoma by regulating MAPK10. (PMID:32572915)
• JNK3 as Therapeutic Target and Biomarker in Neurodegenerative and Neurodevelopmental Brain Diseases. (PMID:32998477)
• Genetic variants in MAPK10 modify renal cell carcinoma susceptibility and clinical outcomes. (PMID:33774030)
• The Roles of c-Jun N-Terminal Kinase (JNK) in Infectious Diseases. (PMID:34502556)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	mapk10	ENSDARG00000102730
mus_musculus	Mapk10	ENSMUSG00000046709
rattus_norvegicus	Mapk10	ENSRNOG00000002079
drosophila_melanogaster	nmo	FBGN0011817
drosophila_melanogaster	CG8565	FBGN0030697
drosophila_melanogaster	SRPK	FBGN0286813
caenorhabditis_elegans		WBGENE00002187
caenorhabditis_elegans		WBGENE00002188
caenorhabditis_elegans		WBGENE00003048
caenorhabditis_elegans		WBGENE00004055
caenorhabditis_elegans		WBGENE00004056
caenorhabditis_elegans		WBGENE00004980
caenorhabditis_elegans	gskl-2	WBGENE00007977
caenorhabditis_elegans	Y106G6E.1	WBGENE00013705

Paralogs (19): MAPK9 (ENSG00000050748), MAPK6 (ENSG00000069956), MOK (ENSG00000080823), NLK (ENSG00000087095), SRPK1 (ENSG00000096063), MAPK1 (ENSG00000100030), MAPK3 (ENSG00000102882), MAPK8 (ENSG00000107643), MAK (ENSG00000111837), MAPK14 (ENSG00000112062), CILK1 (ENSG00000112144), SRPK2 (ENSG00000135250), MAPK4 (ENSG00000141639), MAPK13 (ENSG00000156711), MAPK7 (ENSG00000166484), MAPK15 (ENSG00000181085), SRPK3 (ENSG00000184343), MAPK11 (ENSG00000185386), MAPK12 (ENSG00000188130)

Protein

Protein identifiers

Mitogen-activated protein kinase 10 — P53779 (reviewed: P53779)

Alternative names: MAP kinase p49 3F12, Stress-activated protein kinase 1b, Stress-activated protein kinase JNK3, c-Jun N-terminal kinase 3

All UniProt accessions (69): P53779, A0A1P0B7D2, A0A1W2PNF5, A0A1W2PPM4, A0A1W2PPW1, A0A1W2PPZ3, A0A1W2PQ03, A0A1W2PQX4, A0A1W2PRF2, A0A1W2PRG9, A0A1W2PRZ2, A0A286YEN5, A0A286YEQ0, A0A286YEQ7, A0A286YES0, A0A286YES8, A0A286YES9, A0A286YEV3, A0A286YEV5, A0A286YEV8, A0A286YEW4, A0A286YEW9, A0A286YEX7, A0A286YEY0, A0A286YEY2, A0A286YEZ1, A0A286YF02, A0A286YF04, A0A286YF19, A0A286YF35, A0A286YF43, A0A286YF53, A0A286YF62, A0A286YF80, A0A286YF83, A0A286YF85, A0A286YF95, A0A286YF97, A0A286YFA3, A0A286YFA6, A0A286YFA7, A0A286YFB6, A0A286YFB7, A0A286YFC0, A0A286YFC3, A0A286YFD7, A0A286YFD9, A0A286YFE2, A0A286YFE9, A0A286YFH4, A0A286YFI3, A0A286YFJ0, A0A286YFJ4, A0A286YFJ6, A0A286YFK3, A0A286YFM6, A0A286YFN2, A8MPV1, D6R9C1, D6RAJ0, D6RAU3, D6RBH2, D6RC26, D6RCB1, D6RDG1, D6RFX8, D6RFZ7, D6RJF9, F8W9R5

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration and programmed cell death. Extracellular stimuli such as pro-inflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK10/JNK3. In turn, MAPK10/JNK3 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. Plays regulatory roles in the signaling pathways during neuronal apoptosis. Phosphorylates the neuronal microtubule regulator STMN2. Acts in the regulation of the amyloid-beta precursor protein/APP signaling during neuronal differentiation by phosphorylating APP. Also participates in neurite growth in spiral ganglion neurons. Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the photic regulation of the circadian clock. Phosphorylates JUND and this phosphorylation is inhibited in the presence of MEN1.

Subunit / interactions. Interacts with MAPKBP1. Interacts with MAPK8IP1/JIP-1 and MAPK8IP3/JIP-3/JSAP1. Interacts with SPAG9/MAPK8IP4/JIP4. Interacts with HDAC9. Interacts with ARRB2; the interaction enhances MAPK10 activation by MAP3K5. Interacts with SARM1. Interacts with JUND; interaction is inhibited in the presence of MEN1.

Subcellular location. Cytoplasm. Membrane. Nucleus. Mitochondrion.

Tissue specificity. Specific to a subset of neurons in the nervous system. Present in the hippocampus and areas, cerebellum, striatum, brain stem, and weakly in the spinal cord. Very weak expression in testis and kidney.

Post-translational modifications. Dually phosphorylated on Thr-221 and Tyr-223 by MAP2K4 and MAP2K7, which activates the enzyme. MAP2K7 shows a strong preference for Thr-221 while MAP2K4 phosphorylates Tyr-223 preferentially. Weakly autophosphorylated on threonine and tyrosine residues in vitro. Palmitoylation regulates subcellular location and axonal development.

Disease relevance. A chromosomal aberration involving MAPK10 has been found in a single patient with pharmacoresistant epileptic encephalopathy. Translocation t(Y;4)(q11.2;q21) which causes MAPK10 truncation.

Activity regulation. Activated by threonine and tyrosine phosphorylation by two dual specificity kinases, MAP2K4 and MAP2K7. MAP2K7 phosphorylates MAPK10 on Thr-221 causing a conformational change and a large increase in Vmax. MAP2K4 then phosphorylates Tyr-223 resulting in a further increase in Vmax. Inhibited by dual specificity phosphatases, such as DUSP1. Inhibited by HDAC9.

Domain organisation. The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.

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

Isoforms (3)

UniProt ID	Names	Canonical?
P53779-1	Alpha-2	yes
P53779-2	Alpha-1
P53779-3	3

RefSeq proteins (9): NP_001304996, NP_001304997, NP_001304998, NP_001338553, NP_001338554, NP_001350586, NP_002744, NP_620446, NP_620448* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR003527	MAP_kinase_CS	Conserved_site
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR008351	MAPK_JNK	Family
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR050117	MAPK	Family

Pfam: PF00069

Enzyme classification (BRENDA):

• EC 2.7.11.24 — mitogen-activated protein kinase (BRENDA: 48 organisms, 305 substrates, 720 inhibitors, 27 Km, 20 kcat entries)

Substrate kinetics (BRENDA)

13 substrates with measured Km, best-characterized 13. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.048–0.096	4
ATF2DELTA109	0.002–0.02	2
EGF RECEPTOR PEPTIDE	0.656–2.8	2
ERKSUB	0.127–1.2	2
MEK1ERK	0.0037–0.065	2
MEK2ERK	0.0056–0.03	2
ELKERK	0.0044	1
ERKMEK1	0.344	1
ERKMEK2	0.388	1
ERKSTE7	0.173	1
PROTEIN ATF2	0.0019	1
SCRAMMMEK2	0.096	1
STE7ERK	0.0006	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 (58 total): helix 19, strand 14, turn 7, modified residue 2, lipid moiety-binding region 2, splice variant 2, mutagenesis site 2, compositionally biased region 2, binding site 2, chain 1, domain 1, sequence conflict 1, region of interest 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

65 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
3OY1	X-RAY DIFFRACTION	1.7
7ORF	X-RAY DIFFRACTION	1.7
7KSI	X-RAY DIFFRACTION	1.73
6EMH	X-RAY DIFFRACTION	1.76
4WHZ	X-RAY DIFFRACTION	1.79
6EQ9	X-RAY DIFFRACTION	1.83
7KSK	X-RAY DIFFRACTION	1.84
8WGF	X-RAY DIFFRACTION	1.85
8BZP	X-RAY DIFFRACTION	1.86
2B1P	X-RAY DIFFRACTION	1.9
4W4W	X-RAY DIFFRACTION	1.9
4X21	X-RAY DIFFRACTION	1.95
4H39	X-RAY DIFFRACTION	1.99
2ZDT	X-RAY DIFFRACTION	2
3DA6	X-RAY DIFFRACTION	2
4KKH	X-RAY DIFFRACTION	2
8VNX	X-RAY DIFFRACTION	2
4W4V	X-RAY DIFFRACTION	2.01
4Y46	X-RAY DIFFRACTION	2.04
4Y5H	X-RAY DIFFRACTION	2.06
7KSJ	X-RAY DIFFRACTION	2.06
8VO4	X-RAY DIFFRACTION	2.07
4H3B	X-RAY DIFFRACTION	2.08
2O0U	X-RAY DIFFRACTION	2.1
3TTJ	X-RAY DIFFRACTION	2.1
4Z9L	X-RAY DIFFRACTION	2.1
6EKD	X-RAY DIFFRACTION	2.1
7S1N	X-RAY DIFFRACTION	2.11
7ORE	X-RAY DIFFRACTION	2.18
1PMN	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P53779-F1	80.50	0.64

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): 189 (proton acceptor)

Ligand- & substrate-binding residues (2): 70–78; 93

Post-translational modifications (4): 223, 462, 463, 221

Mutagenesis-validated functional residues (2):

Position	Phenotype
462	loss of palmitoylation.
463	loss of palmitoylation.

Function

Pathways and Gene Ontology

Reactome pathways

31 pathways

ID	Pathway
R-HSA-2559580	Oxidative Stress Induced Senescence
R-HSA-2871796	FCERI mediated MAPK activation
R-HSA-450321	JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
R-HSA-450341	Activation of the AP-1 family of transcription factors
R-HSA-1280215	Cytokine Signaling in Immune system
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-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-2262752	Cellular responses to stress
R-HSA-2454202	Fc epsilon receptor (FCERI) signaling
R-HSA-2559583	Cellular Senescence
R-HSA-448424	Interleukin-17 signaling
R-HSA-449147	Signaling by Interleukins
R-HSA-450282	MAPK targets/ Nuclear events mediated by MAP kinases
R-HSA-450294	MAP kinase activation
R-HSA-8953897	Cellular responses to stimuli
R-HSA-937061	TRIF (TICAM1)-mediated TLR4 signaling
R-HSA-975138	TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
R-HSA-975155	MyD88 dependent cascade initiated on endosome

MSigDB gene sets: 408 (showing top): GOBP_CIRCADIAN_RHYTHM, ATF_B, AP1_01, MULLIGHAN_NPM1_SIGNATURE_3_UP, REACTOME_INNATE_IMMUNE_SYSTEM, KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, PAX4_01, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, KEGG_MAPK_SIGNALING_PATHWAY, SP3_Q3, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, PID_REG_GR_PATHWAY, GOBP_CELLULAR_SENESCENCE, KEGG_FC_EPSILON_RI_SIGNALING_PATHWAY, MODULE_66

GO Biological Process (10): protein phosphorylation (GO:0006468), signal transduction (GO:0007165), JNK cascade (GO:0007254), response to light stimulus (GO:0009416), Fc-epsilon receptor signaling pathway (GO:0038095), regulation of circadian rhythm (GO:0042752), rhythmic process (GO:0048511), cellular senescence (GO:0090398), MAPK cascade (GO:0000165), cellular response to stress (GO:0033554)

GO Molecular Function (11): JUN kinase activity (GO:0004705), MAP kinase kinase activity (GO:0004708), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), MAP kinase activity (GO:0004707), 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), mitochondrion (GO:0005739), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Toll-like Receptor Cascades	7
Immune System	2
Toll Like Receptor 4 (TLR4) Cascade	2
Toll Like Receptor 2 (TLR2) Cascade	2
Cellular Senescence	1
Fc epsilon receptor (FCERI) signaling	1
MAP kinase activation	1
MAPK targets/ Nuclear events mediated by MAP kinases	1
Toll Like Receptor TLR1:TLR2 Cascade	1
Toll Like Receptor TLR6:TLR2 Cascade	1
Innate Immune System	1
Cellular responses to stimuli	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
MAPK cascade	3
cellular process	2
cellular response to stimulus	2
protein kinase activity	2
intracellular membrane-bounded organelle	2
cytoplasm	2
phosphorylation	1
protein modification process	1
cell communication	1
signaling	1
regulation of cellular process	1
response to radiation	1
Fc receptor signaling pathway	1
circadian rhythm	1
regulation of biological process	1
biological_process	1
cellular response to stress	1
intracellular signaling cassette	1
response to stress	1
MAP kinase activity	1
JNK cascade	1
protein serine/threonine/tyrosine kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate 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
protein serine/threonine kinase activity	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
nuclear lumen	1
intracellular anatomical structure	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

55 interactions, top by confidence:

A	B	Type	Score
MAPK9	WDR62	psi-mi:“MI:0914”(association)	0.800
MAPK10	JUN	psi-mi:“MI:0407”(direct interaction)	0.760
MAPK10	JUN	psi-mi:“MI:0217”(phosphorylation reaction)	0.760
JUN	MAPK10	psi-mi:“MI:0915”(physical association)	0.760
MAPK8	WDR62	psi-mi:“MI:0914”(association)	0.730
MAPK10	ARRB1	psi-mi:“MI:0915”(physical association)	0.610
ARRB1	MAPK10	psi-mi:“MI:0407”(direct interaction)	0.610
MAPK10	JUND	psi-mi:“MI:0217”(phosphorylation reaction)	0.560
JUND	MAPK10	psi-mi:“MI:0407”(direct interaction)	0.560
HAX1	MAPK10	psi-mi:“MI:0915”(physical association)	0.550
MAPK10	HAX1	psi-mi:“MI:0914”(association)	0.550
RELA	MAPK10	psi-mi:“MI:0915”(physical association)	0.510
MAPK10	RELA	psi-mi:“MI:0915”(physical association)	0.510
MAPK10	CCT6B	psi-mi:“MI:0915”(physical association)	0.500
MAPK10		psi-mi:“MI:0915”(physical association)	0.490
MAPK10	BRAF	psi-mi:“MI:2364”(proximity)	0.470
MAPK10	BRAF	psi-mi:“MI:0915”(physical association)	0.470
MAPK10	ARRB2	psi-mi:“MI:0407”(direct interaction)	0.440
MAPK10	LDHA	psi-mi:“MI:0915”(physical association)	0.370
MAPK10	UBE3A	psi-mi:“MI:0915”(physical association)	0.370
TNIP1	MAPK10	psi-mi:“MI:0915”(physical association)	0.370
	GAK	psi-mi:“MI:0914”(association)	0.350
	AURKA	psi-mi:“MI:0914”(association)	0.350
MAPK10	ZW10	psi-mi:“MI:0914”(association)	0.350
MAPK10	DDI1	psi-mi:“MI:0914”(association)	0.350
MAPK9	FTH1	psi-mi:“MI:0914”(association)	0.350
MAPK10	FBXW7	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (93): ATF2 (Biochemical Activity), MAPK10 (Two-hybrid), CCT7 (Affinity Capture-MS), CCT6B (Affinity Capture-MS), CCT2 (Affinity Capture-MS), DDI1 (Affinity Capture-MS), CCT2 (Affinity Capture-MS), CCT6B (Affinity Capture-MS), JUN (Biochemical Activity), DUSP9 (Reconstituted Complex), MAPK10 (Biochemical Activity), MAPK10 (Two-hybrid), MAPK8IP3 (Two-hybrid), MAPT (Biochemical Activity), MAPK10 (Reconstituted Complex)

ESM2 similar proteins: A7MBL8, F1QGZ6, O14757, O35099, O35280, O54785, O54992, P45983, P45984, P49185, P49186, P49187, P51955, P53350, P53666, P53668, P53670, P53671, P53779, P62205, P70032, Q07832, Q14680, Q15835, Q16513, Q28GW8, Q2RAX3, Q2TA25, Q32L23, Q3SZW1, Q61241, Q61831, Q61846, Q62673, Q63651, Q6DE87, Q6NU47, Q6NU98, Q8AYC9, Q8IW41

Diamond homologs: A3LUB9, B0XPE4, C0LGF4, C0LGL9, D2HHP1, G0RBE3, O64784, O65530, O94537, P32361, P39073, P45983, P45984, P49185, P49186, P49187, P49336, P53779, P79996, P92208, Q09499, Q17IE8, Q1EBK0, Q1XHL7, Q336M2, Q38SD2, Q3UHC2, Q4P9T2, Q4WJJ0, Q4WKP8, Q54IE8, Q557G1, Q559A2, Q55DJ8, Q55GJ2, Q61831, Q66KH9, Q6CCB0, Q6P3N6, Q751F5

SIGNOR signaling

48 interactions.

A	Effect	B	Mechanism
MAPK10	“down-regulates activity”	ATN1	phosphorylation
MAP2K4	up-regulates	MAPK10	phosphorylation
anthra[1,9-cd]pyrazol-6(2H)-one	down-regulates	MAPK10	“chemical inhibition”
MAPK10	down-regulates	STMN2	phosphorylation
MAPK10	up-regulates	TP53	phosphorylation
NGFR	up-regulates	MAPK10
MAPK10	up-regulates	BAX
MAPK10	down-regulates	SFN	phosphorylation
MAPK10	down-regulates	YWHAZ	phosphorylation
MAPK10	up-regulates	MAPK8IP3	phosphorylation
MAPK8IP3	up-regulates	MAPK10	binding
MAP2K7	up-regulates	MAPK10	phosphorylation
MAPK10	down-regulates	DIABLO	phosphorylation
MAPK10	down-regulates	CDC25C	phosphorylation
MAPK10	up-regulates	JUN	phosphorylation
MAPK14	down-regulates	MAPK10
MAPK10	down-regulates	STMN1	phosphorylation
MAPK10	up-regulates	BCL2L11	phosphorylation
MAPK10	down-regulates	PPM1J	phosphorylation
4-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-[(5-nitro-2-thiazolyl)thio]-1H-1,2,4-triazol-5-one	down-regulates	MAPK10	“chemical inhibition”
profenamine	down-regulates	MAPK10	“chemical inhibition”
MAPK10	up-regulates	APP	phosphorylation
IL1R1	“up-regulates activity”	MAPK10	phosphorylation
MAPK10	“up-regulates activity”	HNRNPK	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 34 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
Signaling by NOTCH	5	29.3×	2e-04
Diseases of signal transduction by growth factor receptors and second messengers	9	17.0×	8e-07
Signaling by Interleukins	6	12.8×	6e-04
Ub-specific processing proteases	5	8.8×	2e-03
Cytokine Signaling in Immune system	6	8.2×	1e-03
Cellular responses to stress	6	7.4×	2e-03
Cellular responses to stimuli	6	6.3×	3e-03
Innate Immune System	6	5.1×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of miRNA transcription	6	51.3×	1e-06
rhythmic process	5	37.0×	4e-05
positive regulation of ERK1 and ERK2 cascade	7	17.5×	3e-05
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	5	11.5×	3e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	7	10.7×	4e-04
protein phosphorylation	5	10.0×	5e-03
positive regulation of gene expression	8	9.1×	3e-04
negative regulation of apoptotic process	8	8.2×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	10
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

4633 predictions. Top by Δscore:

Variant	Effect	Δscore
4:86031363:CTTA:C	donor_loss	1.0000
4:86031365:TA:T	donor_loss	1.0000
4:86031366:A:AC	donor_gain	1.0000
4:86031366:AC:A	donor_gain	1.0000
4:86031367:C:CG	donor_gain	1.0000
4:86031367:CC:C	donor_gain	1.0000
4:86031367:CCT:C	donor_gain	1.0000
4:86031367:CCTTT:C	donor_gain	1.0000
4:86031428:GAGG:G	acceptor_gain	1.0000
4:86031429:AGG:A	acceptor_gain	1.0000
4:86031429:AGGC:A	acceptor_loss	1.0000
4:86031430:GG:G	acceptor_gain	1.0000
4:86031432:C:CC	acceptor_gain	1.0000
4:86031435:CCGAA:C	acceptor_gain	1.0000
4:86031436:C:CT	acceptor_gain	1.0000
4:86031436:C:T	acceptor_gain	1.0000
4:86031437:G:T	acceptor_gain	1.0000
4:86031439:A:AC	acceptor_gain	1.0000
4:86031439:A:C	acceptor_gain	1.0000
4:86064260:TCTTA:T	donor_loss	1.0000
4:86064262:TTA:T	donor_loss	1.0000
4:86064263:T:TG	donor_loss	1.0000
4:86064264:A:AC	donor_gain	1.0000
4:86064264:ACCG:A	donor_gain	1.0000
4:86064265:C:CC	donor_gain	1.0000
4:86064265:CCGC:C	donor_gain	1.0000
4:86064387:CTGG:C	acceptor_gain	1.0000
4:86064388:TGG:T	acceptor_gain	1.0000
4:86064389:GG:G	acceptor_gain	1.0000
4:86064391:C:CA	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000005440 (4:86100934 A>C,G), RS1000007164 (4:86560864 A>C), RS1000008320 (4:86528821 A>G), RS1000010729 (4:86206336 A>G), RS1000028096 (4:86025005 A>G,T), RS1000029376 (4:86052849 C>T), RS1000031436 (4:86242463 C>A), RS1000032795 (4:86515890 T>G), RS1000036159 (4:86117109 A>C), RS1000040134 (4:86241949 C>A), RS1000040569 (4:86079274 C>T), RS1000043614 (4:86470623 C>T), RS1000050766 (4:86149906 C>A), RS1000051347 (4:86157064 A>G), RS1000054303 (4:86425275 A>G)

Disease associations

OMIM: gene MIM:602897 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
Lennox-Gastaut syndrome	Limited	Autosomal dominant

Mondo (2): prostate cancer (MONDO:0008315), Lennox-Gastaut syndrome (MONDO:0016532)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

25 total (25 of 25 shown, HPO-id order):

HPO	Term
HP:0000708	Atypical behavior
HP:0000709	Psychosis
HP:0000718	Aggressive behavior
HP:0000729	Autistic behavior
HP:0000737	Irritability
HP:0000741	Apathy
HP:0000752	Hyperactivity
HP:0001249	Intellectual disability
HP:0001268	Mental deterioration
HP:0001298	Encephalopathy
HP:0001336	Myoclonus
HP:0002069	Bilateral tonic-clonic seizure
HP:0002123	Generalized myoclonic seizure
HP:0002321	Vertigo
HP:0002353	EEG abnormality
HP:0002363	Abnormal brainstem morphology
HP:0002376	Developmental regression
HP:0002527	Falls
HP:0007270	Atypical absence seizure
HP:0007359	Focal-onset seizure
HP:0010818	Generalized tonic seizure
HP:0010819	Atonic seizure
HP:0011195	EEG with focal sharp slow waves
HP:0012075	Personality disorder
HP:0012758	Neurodevelopmental delay

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001275_3	Liver enzyme levels (alanine transaminase)	3.000000e-09
GCST002343_2	Response to cytidine analogues (gemcitabine)	3.000000e-06
GCST002504_2	Peripheral artery disease	2.000000e-06
GCST002875_52	Diisocyanate-induced asthma	1.000000e-06
GCST002930_7	Cobalt levels	2.000000e-06
GCST004110_9	Gait speed in old age	2.000000e-06
GCST009544_7	Cleft lip with or without cleft palate x maternal periconceptional smoking interaction (parent of origin effect)	6.000000e-06
GCST009597_265	Multiple sclerosis	8.000000e-06
GCST010173_175	Triglyceride levels	3.000000e-08
GCST010244_305	Triglyceride levels	5.000000e-12
GCST90013405_123	Liver enzyme levels (alanine transaminase)	2.000000e-14

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0006995	response to diisocyanate
EFO:0003959	cleft lip
EFO:0005939	parental genotype effect measurement
EFO:0009115	tobacco smoke exposure measurement
EFO:0004530	triglyceride measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D065768	Lennox Gastaut Syndrome	C10.228.140.490.493.750; C16.320.495
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2096667 (PROTEIN FAMILY), CHEMBL2637 (SINGLE PROTEIN), CHEMBL3038502 (PROTEIN FAMILY), CHEMBL3885602 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

58 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 591,109 (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
CHEMBL1078178	MOMELOTINIB	4	3,481
CHEMBL1173655	AFATINIB	4	15,144
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL180022	NERATINIB	4	9,404
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL3301607	FILGOTINIB	4	2,905
CHEMBL3301610	ABEMACICLIB	4	7,045
CHEMBL3301622	GILTERITINIB	4	2,395
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL939	GEFITINIB	4	117,814
CHEMBL941	IMATINIB	4	111,611
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL31965	CANERTINIB	3	8,083
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1950289	TANZISERTIB	2
CHEMBL103667	DORAMAPIMOD	2
CHEMBL1090089	PAMAPIMOD	2
CHEMBL1090090	VX-702	2
CHEMBL1230609	FORETINIB	2
CHEMBL1236682	REFAMETINIB	2
CHEMBL1614713	CC-401	2
CHEMBL1721885	SU-014813	2
CHEMBL1738757	REBASTINIB	2

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — JNK subfamily

Most potent curated ligand interactions (15 total), top 15:

Ligand	Action	Affinity	Parameter
JNK-IN-8	Inhibition	9.0	pIC50
tanzisertib	Inhibition	8.22	pIC50
pamapimod	Inhibition	7.72	pKd
J30-8	Inhibition	7.4	pIC50
JNK inhibitor VIII	Inhibition	7.28	pKi
JNK inhibitor V	Inhibition	7.15	pIC50
compound 25c [PMID: 36649216]	Inhibition	7.07	pIC50
SP600125	Inhibition	7.05	pIC50
brimapitide	Inhibition	7.0	pIC50
compound 20 [PMID: 30998356]	Inhibition	6.97	pIC50
JNK inhibitor 9l	Inhibition	6.83	pIC50
JNK inhibitor IX	Inhibition	6.7	pIC50
BOS172722	Inhibition	6.62	pIC50
GNE-3511	Inhibition	6.44	pIC50
compound 11 [PMID: 26431428]	Inhibition	5.68	pIC50

Binding affinities (BindingDB)

497 measured of 727 human assays (733 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-Phenylbenzimidazole deriv. 76	EC50	0.00399 nM
4-(phenylcarbonyl)-N-pyridin-2-yl-1H-imidazole-5-carboxamide	EC50	0.00411 nM
2-[1-(3-pyridinylmethylamino)ethylidene]indene-1,3-dione	EC50	0.00853 nM
5-(2-amino-2-keto-ethoxy)-2-methyl-benzofuran-3-carboxylic acid isopropyl ester	EC50	0.0191 nM
3-[(4-fluorobenzoyl)amino]-1-benzofuran-2-carboxamide	EC50	0.0279 nM
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
JNK-IN-9	IC50	0.5 nM
JNK-IN-10	IC50	0.5 nM
JNK-IN-11	IC50	0.5 nM
JNK-IN-7	IC50	0.75 nM
JNK-IN-5	IC50	0.96 nM
JNK-IN-8	IC50	0.98 nM
N-cyclohexyl-4-[4-(3,4-dichlorophenyl)-2-piperidin-4-yl-1-propyl-1H-imidazol-5-yl]pyrimidin-2-amine	IC50	1.6 nM
Staurosporine	KD	1.7 nM
N-((S)-1-(3-Chloro-4-fluorophenyl)-2-hydroxyethyl)-4-(4-(3-chlorophenyl)-1H-pyrazol-3-yl)-1H-pyrrole-2-carboxamide	KI	2 nM
BMCL19469 Compound 13	IC50	2 nM
2-{[2-({1-[2-(dimethylamino)acetyl]-5-methoxy-2,3-dihydro-1H-indol-6-yl}amino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino}-6-fluoro-N-methylbenzamide	IC50	2 nM
JNK3 inhibitor 2	KI	3 nM	US-8563583: Pyridone analogs useful as melanin concentrating hormone receptor-1 antagonists
JNK3 inhibitor 4	KI	4 nM	US-8563583: Pyridone analogs useful as melanin concentrating hormone receptor-1 antagonists
2-fluoro-6-{[2-({2-methoxy-5-[4-(propan-2-yl)piperazin-1-yl]phenyl}amino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino}benzamide	IC50	4 nM
JNK3 inhibitor 3	KI	7 nM	US-8563583: Pyridone analogs useful as melanin concentrating hormone receptor-1 antagonists
4-(4-(3-Chlorophenyl)-1H-pyrazol-3-yl)-N-(1-(3,5-dichlorophenyl)-2-hydroxyethyl)-1H-pyrrole-2-carboxamide	KI	7 nM
Aminopyrazole inhibitor, 3576	IC50	7 nM
N-cyclopropyl-4-[4-(3,4-dichlorophenyl)-2-(1-methylpiperidin-4-yl)-1-propyl-1H-imidazol-5-yl]pyrimidin-2-amine	IC50	7.1 nM
4-(4-Fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)-1H-imidazole	KD	9.8 nM
JNK-IN-12	IC50	11 nM
4-[4-(4-fluorophenyl)-2-(4-methanesulfinylphenyl)-1H-imidazol-5-yl]pyridine	KD	12 nM
4-(4-(3-Chlorophenyl)-1H-pyrazol-3-yl)-N-(1-(4-chlorophenyl)-2-hydroxyethyl)-1H-pyrrole-2-carboxamide	KI	14 nM
N-[4-amino-5-cyano-6-(propan-2-yloxy)pyridin-2-yl]-2-(4-methanesulfonyl-2,5-dimethoxyphenyl)acetamide	KI	18 nM
2-fluoro-6-{[2-({2-methoxy-4-methyl-5-[4-(propan-2-yl)piperazin-1-yl]phenyl}amino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino}benzamide	IC50	20 nM
4-[4-(3-chlorophenyl)-1H-pyrazol-3-yl]-N-[1-(3,4-difluorophenyl)-2-hydroxyethyl]-1H-pyrrole-2-carboxamide	KI	22 nM
Aminopyrazole inhibitor, 3528	IC50	23 nM
4-[4-(3-chlorophenyl)-1H-pyrazol-3-yl]-N-[1-(3-fluorophenyl)-2-hydroxyethyl]-1H-pyrrole-2-carboxamide	KI	24 nM
Aminopyrazole inhibitor, 3451	IC50	25 nM
4-[4-(3-chlorophenyl)-1H-pyrazol-3-yl]-N-[(1S)-2-hydroxy-1-phenylethyl]-1H-pyrrole-2-carboxamide	KI	35 nM
4-[4-(3-chlorophenyl)-1H-pyrazol-3-yl]-N-[(3,4-difluorophenyl)methyl]-1H-pyrrole-2-carboxamide	KI	40 nM
4-[4-(3-chlorophenyl)-1H-pyrazol-3-yl]-N-{2-hydroxy-1-[4-(trifluoromethyl)phenyl]ethyl}-1H-pyrrole-2-carboxamide	KI	44 nM
N-(4-Amino-5-cyano-6-ethoxypyridin-2-yl)-2-(2,5-dimethoxyphenyl)acetamide	KI	52 nM
Aminopyrazole inhibitor, 4326	IC50	55 nM
aryl piperidine, 9b	IC50	60 nM
N-(4-amino-5-chloro-6-ethoxypyridin-2-yl)-2-(4-methanesulfonyl-2,5-dimethoxyphenyl)acetamide	KI	61 nM
4-(4-(3-Chlorophenyl)-1H-pyrazol-3-yl)-N-(1-(4-fluorophenyl)-2-hydroxyethyl)-1H-pyrrole-2-carboxamide	KI	63 nM
Example 1	IC50	65 nM	US-10301291: Imidazole derivative having JNK inhibitory activity and use thereof
Example 3	IC50	65 nM	US-10301291: Imidazole derivative having JNK inhibitory activity and use thereof
Example 5	IC50	65 nM	US-10301291: Imidazole derivative having JNK inhibitory activity and use thereof
Example 6	IC50	65 nM	US-10301291: Imidazole derivative having JNK inhibitory activity and use thereof
Example 10	IC50	65 nM	US-10301291: Imidazole derivative having JNK inhibitory activity and use thereof
Example 11	IC50	65 nM	US-10301291: Imidazole derivative having JNK inhibitory activity and use thereof
Example 13	IC50	65 nM	US-10301291: Imidazole derivative having JNK inhibitory activity and use thereof
Example 14	IC50	65 nM	US-10301291: Imidazole derivative having JNK inhibitory activity and use thereof

ChEMBL bioactivities

1927 potent at pChembl≥5 of 2246 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.17	IC50	0.068	nM	CHEMBL210618
9.97	IC50	0.107	nM	CHEMBL4546504
9.80	IC50	0.16	nM	CHEMBL3220502
9.60	IC50	0.25	nM	CHEMBL3220499
9.55	IC50	0.28	nM	CHEMBL3220493
9.55	IC50	0.28	nM	CHEMBL3220497
9.52	IC50	0.3	nM	CHEMBL3220496
9.52	IC50	0.3	nM	CHEMBL3220493
9.52	IC50	0.3	nM	CHEMBL4077018
9.51	IC50	0.31	nM	CHEMBL3220498
9.42	IC50	0.379	nM	CHEMBL5403678
9.38	IC50	0.42	nM	CHEMBL3220494
9.30	IC50	0.5	nM	CHEMBL3393608
9.25	IC50	0.564	nM	CHEMBL5423620
9.22	IC50	0.6	nM	CHEMBL4062023
9.22	IC50	0.607	nM	CHEMBL5411160
9.15	IC50	0.7	nM	CHEMBL3393607
9.14	IC50	0.73	nM	CHEMBL5398642
9.14	IC50	0.716	nM	CHEMBL5436023
9.12	IC50	0.75	nM	CHEMBL3393607
9.11	IC50	0.78	nM	CHEMBL3220495
9.11	IC50	0.77	nM	CHEMBL3220500
9.11	IC50	0.779	nM	CHEMBL5401511
9.10	IC50	0.8	nM	CHEMBL3220495
9.10	Ki	0.7943	nM	CHEMBL377408
9.01	IC50	0.98	nM	CHEMBL2216824
9.00	IC50	1	nM	CHEMBL3099975
9.00	IC50	1	nM	CHEMBL2216824
9.00	Kd	1	nM	TANZISERTIB
9.00	IC50	1	nM	CHEMBL4861739
9.00	IC50	1	nM	CHEMBL4875508
9.00	IC50	1	nM	CHEMBL5396715
9.00	IC50	1	nM	CHEMBL5574740
9.00	IC50	1	nM	CHEMBL6177069
8.97	IC50	1.08	nM	CHEMBL5424946
8.96	IC50	1.11	nM	CHEMBL5429577
8.92	IC50	1.2	nM	CHEMBL3217784
8.92	Ki	1.2	nM	CHEMBL4633869
8.92	IC50	1.2	nM	CHEMBL5408675
8.92	IC50	1.2	nM	CHEMBL5431060
8.90	IC50	1.259	nM	CHEMBL194806
8.89	IC50	1.3	nM	CHEMBL6165786
8.85	IC50	1.4	nM	CHEMBL194806
8.80	IC50	1.6	nM	CHEMBL252967
8.80	IC50	1.6	nM	CHEMBL437747
8.76	IC50	1.72	nM	CHEMBL5430858
8.75	IC50	1.76	nM	CHEMBL5399794
8.74	Kd	1.8	nM	CHEMBL2425628
8.72	IC50	1.9	nM	CHEMBL3356001
8.72	IC50	1.9	nM	CHEMBL3355999

PubChem BioAssay actives

1676 with measured affinity, of 4098 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
N-(4-amino-5-cyano-6-ethoxy-2-pyridinyl)-2-(2,5-dimethoxyphenyl)acetamide	2031914: Inhibition of human JNK3 incubated for 40 mins in presence of ATP and [gamma33P-ATP] by scintillation counting method	ic50	0.0001	uM
4-[[5-chloro-4-(4-hydroxy-4-methylcyclohexyl)oxy-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-N,N-dimethyl-3-[(2R)-1,1,1-trifluoropropan-2-yl]oxybenzamide	1551603: Inhibition of recombinant human full length N-terminal GST-tagged JNK3 expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.0001	uM
2-[[5-chloro-2-[4-(2-oxopyrrolidin-1-yl)anilino]pyrimidin-4-yl]amino]benzamide	1189542: Inhibition of JNK3 (unknown origin) by time-resolved fluorescence assay	ic50	0.0002	uM
N-[4-[[4-[5-(4-fluorophenyl)-3-methyl-2-methylsulfanylimidazol-4-yl]-2-pyridinyl]amino]phenyl]-3-(prop-2-enoylamino)benzamide	1436104: Inhibition of recombinant 6x-His-tagged JNK3 (39 to 402 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) assessed as reduction in ATF2 phosphorylation measured after 50 mins by ELISA	ic50	0.0003	uM
2-[[5-chloro-2-(4-morpholin-4-ylanilino)pyrimidin-4-yl]amino]benzamide	1189542: Inhibition of JNK3 (unknown origin) by time-resolved fluorescence assay	ic50	0.0003	uM
3-[2-[[(3S)-1-(cyclopropanecarbonyl)piperidin-3-yl]amino]pyrimidin-4-yl]-2-(3,4-dichlorophenyl)-5,6-dihydro-4H-cyclopenta[d]imidazole-5-carboxamide	2032526: Inhibition of JNK3 (unknown origin) using ATF2 as substrate incubated for 40 mins in presence of [gamma33P]ATP by scintillation counting analysis	ic50	0.0004	uM
5-[[(E)-4-(dimethylamino)but-2-enoyl]amino]-2-methyl-N-[4-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]benzamide	1799705: JNK Kinase Assay from Article 10.1016/j.chembiol.2011.11.010: “Discovery of potent and selective covalent inhibitors of JNK.”	ic50	0.0005	uM
3-[[(E)-4-(dimethylamino)but-2-enoyl]amino]-4-methyl-N-[4-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]benzamide	1799705: JNK Kinase Assay from Article 10.1016/j.chembiol.2011.11.010: “Discovery of potent and selective covalent inhibitors of JNK.”	ic50	0.0005	uM
3-[[(E)-4-(dimethylamino)but-2-enoyl]amino]-N-[4-[[4-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-yl]amino]phenyl]benzamide	1189579: Inhibition of JNK3 (unknown origin) after 1 hr incubation	ic50	0.0005	uM
N-[4-[[4-[4-(4-fluorophenyl)-2-methylsulfanyl-1H-imidazol-5-yl]-2-pyridinyl]amino]phenyl]-3-(prop-2-enoylamino)benzamide	1436104: Inhibition of recombinant 6x-His-tagged JNK3 (39 to 402 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) assessed as reduction in ATF2 phosphorylation measured after 50 mins by ELISA	ic50	0.0006	uM
ethyl 3-[2-[[(3R)-1-(cyclopropanecarbonyl)piperidin-3-yl]amino]pyrimidin-4-yl]-2-(3,4-dichlorophenyl)-5,6-dihydro-4H-cyclopenta[d]imidazole-5-carboxylate	2032526: Inhibition of JNK3 (unknown origin) using ATF2 as substrate incubated for 40 mins in presence of [gamma33P]ATP by scintillation counting analysis	ic50	0.0006	uM
3-[2-[[(3S)-1-(cyclopropanecarbonyl)piperidin-3-yl]amino]pyrimidin-4-yl]-N-methyl-2-naphthalen-2-yl-5,6-dihydro-4H-cyclopenta[d]imidazole-5-carboxamide	2032526: Inhibition of JNK3 (unknown origin) using ATF2 as substrate incubated for 40 mins in presence of [gamma33P]ATP by scintillation counting analysis	ic50	0.0006	uM
3-[2-[[(3R)-1-(cyclopropanecarbonyl)piperidin-3-yl]amino]pyrimidin-4-yl]-2-(3,4-dichlorophenyl)-5,6-dihydro-4H-cyclopenta[d]imidazole-5-carboxamide	2032526: Inhibition of JNK3 (unknown origin) using ATF2 as substrate incubated for 40 mins in presence of [gamma33P]ATP by scintillation counting analysis	ic50	0.0007	uM
ethyl 3-[2-[[(3S)-1-(cyclopropanecarbonyl)piperidin-3-yl]amino]pyrimidin-4-yl]-2-naphthalen-2-yl-5,6-dihydro-4H-cyclopenta[d]imidazole-5-carboxylate	2032526: Inhibition of JNK3 (unknown origin) using ATF2 as substrate incubated for 40 mins in presence of [gamma33P]ATP by scintillation counting analysis	ic50	0.0007	uM
3-[[(E)-4-(dimethylamino)but-2-enoyl]amino]-N-[4-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]benzamide	1189579: Inhibition of JNK3 (unknown origin) after 1 hr incubation	ic50	0.0007	uM
ethyl 3-[2-[[(3R)-1-(cyclopropanecarbonyl)piperidin-3-yl]amino]pyrimidin-4-yl]-2-naphthalen-2-yl-5,6-dihydro-4H-cyclopenta[d]imidazole-5-carboxylate	2032526: Inhibition of JNK3 (unknown origin) using ATF2 as substrate incubated for 40 mins in presence of [gamma33P]ATP by scintillation counting analysis	ic50	0.0008	uM
2-[[5-chloro-2-(2-methoxy-4-morpholin-4-ylanilino)pyrimidin-4-yl]amino]benzamide	1189542: Inhibition of JNK3 (unknown origin) by time-resolved fluorescence assay	ic50	0.0008	uM
3-[4-[(2-chlorophenyl)carbamoylamino]pyrazol-1-yl]-N-(1-pyrrolidin-3-ylpyrazol-4-yl)benzamide	1170948: Inhibition of JNK3alpha1 (unknown origin) after 1 hr by homogeneous time-resolved fluorescence assay	ic50	0.0010	uM
4-[[9-[(3S)-oxolan-3-yl]-8-(2,4,6-trifluoroanilino)purin-2-yl]amino]cyclohexan-1-ol	1425057: 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	0.0010	uM
2-[3-[2-[[(3S)-1-(cyclopropanecarbonyl)piperidin-3-yl]amino]pyrimidin-4-yl]-2-naphthalen-2-ylimidazol-4-yl]acetonitrile	1988010: Inhibition of JNK3 (unknown origin) using ATF2 as substrate incubated for 40 mins in presence of [gamma33P]ATP by scintillation counting analysis	ic50	0.0010	uM
4-[5-(2-chloroanilino)-6-fluoroindazol-1-yl]-N-cyclopropylthiophene-2-carboxamide	1780530: Inhibition of JNK3alpha1 (unknown origin) using biotinylated FL-ATF-2 as substrate measured after 22 mins by homogeneous time-resolved fluorescence analysis	ic50	0.0010	uM
4-[5-(2-chloroanilino)indazol-1-yl]-N-[(3S)-1-(trideuteriomethyl)pyrrolidin-3-yl]thiophene-2-carboxamide	1780530: Inhibition of JNK3alpha1 (unknown origin) using biotinylated FL-ATF-2 as substrate measured after 22 mins by homogeneous time-resolved fluorescence analysis	ic50	0.0010	uM
2-[1-[3-[[1-(cyclopropanecarbonyl)piperidin-3-yl]amino]phenyl]-2-naphthalen-2-ylimidazol-4-yl]acetonitrile	2091879: Inhibition of JNK3 (unknown origin)	ic50	0.0010	uM
3-(prop-2-enoylamino)-N-[4-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]benzamide	1799705: JNK Kinase Assay from Article 10.1016/j.chembiol.2011.11.010: “Discovery of potent and selective covalent inhibitors of JNK.”	ic50	0.0010	uM
3-[[(E)-4-(dimethylamino)but-2-enoyl]amino]-N-[3-methyl-4-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]benzamide	1189579: Inhibition of JNK3 (unknown origin) after 1 hr incubation	ic50	0.0010	uM
4-(4-fluorophenyl)-3-[2-(4-morpholin-4-ylanilino)-4-pyridinyl]-2H-1,2-oxazol-5-one	1061729: Inhibition of JNK3 (39 to 402 amino acids) (unknown origin) expressed in Escherichia coli BL21(DE3) using biotinylated ATF2 as substrate after 15 mins by HTRF assay	ic50	0.0010	uM
3-[2-[[(3R)-1-(cyclopropanecarbonyl)piperidin-3-yl]amino]pyrimidin-4-yl]-N-methyl-2-naphthalen-2-yl-5,6-dihydro-4H-cyclopenta[d]imidazole-5-carboxamide	2032526: Inhibition of JNK3 (unknown origin) using ATF2 as substrate incubated for 40 mins in presence of [gamma33P]ATP by scintillation counting analysis	ic50	0.0011	uM
ethyl 3-[2-[[(3S)-1-(cyclopropanecarbonyl)piperidin-3-yl]amino]pyrimidin-4-yl]-2-(3,4-dichlorophenyl)-5,6-dihydro-4H-cyclopenta[d]imidazole-5-carboxylate	2032526: Inhibition of JNK3 (unknown origin) using ATF2 as substrate incubated for 40 mins in presence of [gamma33P]ATP by scintillation counting analysis	ic50	0.0011	uM
2-[2-(2,4-dimethylphenyl)phenyl]-1-ethyl-N-methylbenzimidazole-5-carboxamide	1973687: Binding affinity to JNK3 (unknown origin) assessed as inhibition constant	ki	0.0012	uM
3-[2-[[(3S)-1-(cyclopropanecarbonyl)piperidin-3-yl]amino]pyrimidin-4-yl]-2-(3,4-dichlorophenyl)-N-methyl-5,6-dihydro-4H-cyclopenta[d]imidazole-5-carboxamide	2032526: Inhibition of JNK3 (unknown origin) using ATF2 as substrate incubated for 40 mins in presence of [gamma33P]ATP by scintillation counting analysis	ic50	0.0012	uM
ethyl 2-(1,3-benzodioxol-5-yl)-3-[2-[[(3R)-1-(cyclopropanecarbonyl)piperidin-3-yl]amino]pyrimidin-4-yl]-5,6-dihydro-4H-cyclopenta[d]imidazole-5-carboxylate	2032526: Inhibition of JNK3 (unknown origin) using ATF2 as substrate incubated for 40 mins in presence of [gamma33P]ATP by scintillation counting analysis	ic50	0.0012	uM
3-[6-(2-chloroanilino)-1H-indazol-3-yl]-N-piperidin-4-ylbenzamide	470876: Inhibition of JNK3 by high throughput screening	ic50	0.0013	uM
N-cyclopropyl-4-[5-(3,4-dichlorophenyl)-2-(1-methylpiperidin-4-yl)-3-propylimidazol-4-yl]pyrimidin-2-amine	311015: Inhibition of JNK3	ic50	0.0016	uM
N-cyclohexyl-4-[5-(3,4-dichlorophenyl)-2-piperidin-4-yl-3-propylimidazol-4-yl]pyrimidin-2-amine	1797457: Homogeneous Time-Resolved Fluorescence (HTRF) Enzyme Assay from Article 10.1016/S1074-5521(03)00159-5: “The structure of JNK3 in complex with small molecule inhibitors: structural basis for potency and selectivity.”	ic50	0.0016	uM
3-[2-[[(3R)-1-(cyclopropanecarbonyl)piperidin-3-yl]amino]pyrimidin-4-yl]-2-naphthalen-2-yl-5,6-dihydro-4H-cyclopenta[d]imidazole-5-carboxamide	2032526: Inhibition of JNK3 (unknown origin) using ATF2 as substrate incubated for 40 mins in presence of [gamma33P]ATP by scintillation counting analysis	ic50	0.0017	uM
3-[2-[[(3S)-1-(cyclopropanecarbonyl)piperidin-3-yl]amino]pyrimidin-4-yl]-2-naphthalen-2-yl-5,6-dihydro-4H-cyclopenta[d]imidazole-5-carboxamide	2032526: Inhibition of JNK3 (unknown origin) using ATF2 as substrate incubated for 40 mins in presence of [gamma33P]ATP by scintillation counting analysis	ic50	0.0018	uM
(4-hydroxypiperidin-1-yl)-[4-[[4-[4-(3-methylsulfonylpropoxy)indol-1-yl]pyrimidin-2-yl]amino]cyclohexyl]methanone	769510: Binding affinity to JNK3 (unknown origin)	kd	0.0018	uM
4-[6-(2-chloroanilino)-1H-indazol-3-yl]-N-[2-(dimethylamino)ethyl]benzamide	254829: Inhibitory concentration against c-Jun N-terminal kinase 3	ic50	0.0019	uM
4-N-[4-[2-[4-(1H-benzimidazol-2-ylamino)naphthalen-1-yl]oxy-3-pyridinyl]pyrimidin-2-yl]cyclohexane-1,4-diamine	1177295: Inhibition of human wild type JNK3 using biotinylated ATF2 substrate assessed as phosphorylation at thr53 on ATF2 by fluorescent plate reader	ic50	0.0019	uM
4-N-[4-[2-[4-(1H-benzimidazol-2-ylamino)-2-methylnaphthalen-1-yl]oxy-3-pyridinyl]pyrimidin-2-yl]cyclohexane-1,4-diamine	1177295: Inhibition of human wild type JNK3 using biotinylated ATF2 substrate assessed as phosphorylation at thr53 on ATF2 by fluorescent plate reader	ic50	0.0019	uM
N-[4-[[4-[4-(4-fluorophenyl)-2-methylsulfanyl-1H-imidazol-5-yl]-2-pyridinyl]amino]phenyl]-3-(propanoylamino)benzamide	1436104: Inhibition of recombinant 6x-His-tagged JNK3 (39 to 402 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) assessed as reduction in ATF2 phosphorylation measured after 50 mins by ELISA	ic50	0.0020	uM
N-[4-[[4-[5-(4-fluorophenyl)-3-methyl-2-methylsulfanylimidazol-4-yl]-2-pyridinyl]amino]phenyl]-2-methyl-3-(prop-2-enoylamino)benzamide	1436104: Inhibition of recombinant 6x-His-tagged JNK3 (39 to 402 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) assessed as reduction in ATF2 phosphorylation measured after 50 mins by ELISA	ic50	0.0020	uM
N-[4-[[4-(5-methyl-2-methylsulfanyl-1H-imidazol-4-yl)-2-pyridinyl]amino]phenyl]-3-(prop-2-enoylamino)benzamide	1436104: Inhibition of recombinant 6x-His-tagged JNK3 (39 to 402 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) assessed as reduction in ATF2 phosphorylation measured after 50 mins by ELISA	ic50	0.0020	uM
N-[4-[[4-[5-(4-fluorophenyl)-3-methyl-2-methylsulfanylimidazol-4-yl]-2-pyridinyl]amino]-3-methylphenyl]-3-(prop-2-enoylamino)benzamide	1436104: Inhibition of recombinant 6x-His-tagged JNK3 (39 to 402 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) assessed as reduction in ATF2 phosphorylation measured after 50 mins by ELISA	ic50	0.0020	uM
2-[3-[2-[[(3S)-1-(cyclopropanecarbonyl)piperidin-3-yl]amino]pyrimidin-4-yl]-2-(3,4-dichlorophenyl)imidazol-4-yl]acetonitrile	2031914: Inhibition of human JNK3 incubated for 40 mins in presence of ATP and [gamma33P-ATP] by scintillation counting method	ic50	0.0020	uM
4-[5-(2-chloroanilino)-6-fluoroindazol-1-yl]-N-[(3S)-oxolan-3-yl]thiophene-2-carboxamide	1780530: Inhibition of JNK3alpha1 (unknown origin) using biotinylated FL-ATF-2 as substrate measured after 22 mins by homogeneous time-resolved fluorescence analysis	ic50	0.0020	uM
4-[5-(2-chloroanilino)-6-fluoroindazol-1-yl]-N-(oxan-4-yl)thiophene-2-carboxamide	1780530: Inhibition of JNK3alpha1 (unknown origin) using biotinylated FL-ATF-2 as substrate measured after 22 mins by homogeneous time-resolved fluorescence analysis	ic50	0.0020	uM
4-[5-(2-chloroanilino)-6-fluoroindazol-1-yl]-N-propan-2-ylthiophene-2-carboxamide	1780530: Inhibition of JNK3alpha1 (unknown origin) using biotinylated FL-ATF-2 as substrate measured after 22 mins by homogeneous time-resolved fluorescence analysis	ic50	0.0020	uM
4-[5-(2-chloro-6-fluoroanilino)-6-fluoroindazol-1-yl]-N-methylthiophene-2-carboxamide	1780530: Inhibition of JNK3alpha1 (unknown origin) using biotinylated FL-ATF-2 as substrate measured after 22 mins by homogeneous time-resolved fluorescence analysis	ic50	0.0020	uM
4-[5-(2-chloro-6-fluoroanilino)pyrazolo[3,4-b]pyridin-1-yl]-N-methylthiophene-2-carboxamide	1780530: Inhibition of JNK3alpha1 (unknown origin) using biotinylated FL-ATF-2 as substrate measured after 22 mins by homogeneous time-resolved fluorescence analysis	ic50	0.0020	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects expression, decreases expression	5
sodium arsenite	affects methylation, decreases activity, decreases expression	3
Tobacco Smoke Pollution	affects expression, decreases expression, decreases methylation	3
bisphenol A	affects cotreatment, affects methylation, increases methylation, increases phosphorylation	2
trichostatin A	affects cotreatment, decreases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Silicon Dioxide	decreases expression	2
aristolochic acid I	decreases expression	1
beta-N-methylamino-L-alanine	decreases expression	1
methylmercuric chloride	decreases expression	1
mangiferin	increases expression, decreases reaction, increases activity	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
sulindac sulfide	increases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects response to substance	1
pentanal	decreases expression	1
arsenic trichloride	increases expression, increases abundance	1
aluminum maltolate	increases activity, increases expression, decreases reaction	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	increases phosphorylation, increases reaction	1
CGP 52608	affects binding, increases reaction	1
2,4,3’,5’-tetramethoxystilbene	increases phosphorylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Pt(O,O’-acac)(gamma-acac)(DMS)	increases phosphorylation, increases reaction, increases activity	1
bisphenol S	affects methylation	1
(+)-JQ1 compound	decreases expression	1
Bortezomib	affects cotreatment, decreases reaction, increases activity, increases phosphorylation, increases abundance	1

ChEMBL screening assays

900 unique, capped per target: 892 binding, 7 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000440	Binding	Inhibition of human JNK expressed in baculovirus insect cell system	Mixed-lineage kinase 1 and mixed-lineage kinase 3 subtype-selective dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5-ones: optimization, mixed-lineage kinase 1 crystallography, and oral in vivo activity in 1-methyl-4-phenyltetrahydropyridine models. — J Med Chem
CHEMBL853927	Functional	Inhibition of PcJun phosphorylation in HepG2 cells	Aminopyridine carboxamides as c-Jun N-terminal kinase inhibitors: targeting the gatekeeper residue and beyond. — Bioorg Med Chem Lett
CHEMBL4424888	ADMET	Inhibition of full-length human N-terminal His6-tagged JNK3 expressed in baculovirus infected Sf21 insect cells using ATF2 as substrate	Optimization of an azetidine series as inhibitors of colony stimulating factor-1 receptor (CSF-1R) Type II to lead to the clinical candidate JTE-952. — Bioorg Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9JK	Ubigene HEK293 MAPK10 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01370486	PHASE4	WITHDRAWN	Melatonin Versus Placebo in the Lennox-Gastaut Syndrome: Neurophysiological and Neuropsychological Effects
NCT02731300	PHASE4	COMPLETED	Transcranial Direct Current Stimulation, Treatment of Childhood Drug-Resistant Lennox-Gastaut Syndrome, A Pilot Study
NCT04133480	PHASE4	WITHDRAWN	Investigation of Cognitive Outcomes With Cannabidiol Oral Solution
NCT05044819	PHASE4	ACTIVE_NOT_RECRUITING	Assessment of Potential for Chronic Liver Injury in Participants Treated With Epidiolex (Cannabidiol) Oral Solution
NCT06924827	PHASE4	NOT_YET_RECRUITING	A Study to Investigate the Transition of Children From ‘Artisanal Cannabidiol (CBD) to Epidiolex
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer