MAPK9

Summary

MAPK9 (mitogen-activated protein kinase 9, HGNC:6886) is a protein-coding gene on chromosome 5q35.3, encoding Mitogen-activated protein kinase 9 (P45984). Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death.

The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase targets specific transcription factors, and thus mediates immediate-early gene expression in response to various cell stimuli. It is most closely related to MAPK8, both of which are involved in UV radiation induced apoptosis, thought to be related to the cytochrome c-mediated cell death pathway. This gene and MAPK8 are also known as c-Jun N-terminal kinases. This kinase blocks the ubiquitination of tumor suppressor p53, and thus it increases the stability of p53 in nonstressed cells. Studies of this gene’s mouse counterpart suggest a key role in T-cell differentiation. Several alternatively spliced transcript variants encoding distinct isoforms have been reported.

Source: NCBI Gene 5601 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 49 total
• Druggable target: yes — 58 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002752

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6886
Approved symbol	MAPK9
Name	mitogen-activated protein kinase 9
Location	5q35.3
Locus type	gene with protein product
Status	Approved
Aliases	JNK2, p54a, SAPK
Ensembl gene	ENSG00000050748
Ensembl biotype	protein_coding
OMIM	602896
Entrez	5601

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 11 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000343111, ENST00000347470, ENST00000393360, ENST00000393362, ENST00000397072, ENST00000425491, ENST00000452135, ENST00000455781, ENST00000520212, ENST00000523135, ENST00000523583, ENST00000524170, ENST00000539014, ENST00000929130, ENST00000946840

RefSeq mRNA: 13 — MANE Select: NM_002752 NM_001135044, NM_001308244, NM_001364607, NM_001364608, NM_001364609, NM_001364610, NM_001364611, NM_001364612, NM_001364613, NM_002752, NM_139068, NM_139069, NM_139070

CCDS: CCDS43409, CCDS43410, CCDS4453, CCDS4454, CCDS47356, CCDS78103

Canonical transcript exons

ENST00000452135 — 12 exons

Exon	Start	End
ENSE00001391375	180280440	180280608
ENSE00001394598	180238332	180238403
ENSE00002114291	180233143	180236526
ENSE00003466166	180241031	180241155
ENSE00003466247	180248973	180249138
ENSE00003492428	180269280	180269409
ENSE00003492617	180261684	180261822
ENSE00003520516	180242573	180242755
ENSE00003556603	180247439	180247510
ENSE00003560064	180239924	180239987
ENSE00003788751	180264781	180264839
ENSE00003904399	180291848	180292083

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 97.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.7445 / max 237.9970, expressed in 1800 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
65287	8.0354	1757
65286	7.5171	1749
65285	0.1921	58

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	97.06	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.49	gold quality
cerebellum	UBERON:0002037	95.87	gold quality
cerebellar cortex	UBERON:0002129	95.87	gold quality
cerebellar hemisphere	UBERON:0002245	95.86	gold quality
superior frontal gyrus	UBERON:0002661	95.60	gold quality
prefrontal cortex	UBERON:0000451	95.55	gold quality
pons	UBERON:0000988	95.46	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.28	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.27	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.24	gold quality
parietal lobe	UBERON:0001872	95.16	gold quality
postcentral gyrus	UBERON:0002581	95.05	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.94	gold quality
primary visual cortex	UBERON:0002436	94.78	gold quality
occipital lobe	UBERON:0002021	94.54	gold quality
paraflocculus	UBERON:0005351	94.37	gold quality
frontal cortex	UBERON:0001870	94.34	gold quality
neocortex	UBERON:0001950	94.12	gold quality
cingulate cortex	UBERON:0003027	94.11	gold quality
anterior cingulate cortex	UBERON:0009835	94.05	gold quality
superior vestibular nucleus	UBERON:0007227	94.03	gold quality
cerebral cortex	UBERON:0000956	93.96	gold quality
right frontal lobe	UBERON:0002810	93.80	gold quality
cerebellar vermis	UBERON:0004720	93.76	gold quality
endometrium epithelium	UBERON:0004811	93.63	gold quality
frontal pole	UBERON:0002795	93.49	gold quality
substantia nigra pars compacta	UBERON:0001965	93.41	gold quality
telencephalon	UBERON:0001893	93.33	gold quality
orbitofrontal cortex	UBERON:0004167	93.19	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	1586.35
E-MTAB-3929	yes	784.25
E-ANND-3	yes	7.40
E-GEOD-124858	no	186.13

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ARID3B, ATF2, HIF1A, NFATC1, NFKB, NFKBIA, STAT3, TBP, VSX2

miRNA regulators (miRDB)

94 targeting MAPK9, 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-5692A	100.00	74.40	6850
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-579-3P	99.86	71.66	3628

Literature-anchored findings (GeneRIF, showing 40)

• Protein kinase D complexes with C-Jun N-terminal kinase via activation loop phosphorylation and phosphorylates the C-Jun N-terminus. (PMID:11948398)
• involves TRAF4 in oxidative activation (PMID:12023963)
• JNK is required for growth of prostate carcinoma cells in vitro and in vivo (PMID:12538493)
• biochemical pathway exists wherein fluid shear activates cyclooxygenase-2, via a c-Jun N-terminal kinase2/c-Jun-dependent pathway, which in turn elicits downstream prostaglandin EP2 and EP3a1 receptor mRNA synthesis (PMID:12743126)
• activation of JNK is important for the induction of apoptosis following stresses that function at different cell cycle phases, and that basal JNK activity is necessary to promote proliferation and maintain diploidy in breast cancer cells (PMID:14724588)
• JNK2 functions in maintaining the genomic stability of mammalian cells by signaling that is independent of cyclin-dependent kinase 1/cyclin B1 down-regulation. (PMID:15262983)
• SAPKgamma/JNK1 and SAPKalpha/JNK2 may be important mediators of stress-induced responses in early implanting conceptuses that could mediate embryo loss. (PMID:15474087)
• crucial role of JNK signalling pathway in N. meningitidis invasion in human brain microvascular endothelial cells (PMID:15527495)
• analysis of the regions required for JNK2alpha2 autophosphorylation (PMID:15637069)
• ERK1/2 and JNK1/2 signaling is stimulated by radiation and can promote cell cycle progression in human colon cancer cells (PMID:15655348)
• p53 participates in a feedback mechanism with JNK to regulate the apoptotic process and is oppositely regulated by JNK1 and JNK2. (PMID:15778501)
• Some green tea catechins induce pro-MMP-7 production via O2- production and the activation of JNK1/2. (PMID:15860507)
• JIP1 and JIP3, have a cross-talk that leads to the regulation of the ASK1-SEK1-JNK signal during glucose deprivation; cross-talk between JIP3 and JIP1 is mediated through SEK1-JNK2 and Akt1. (PMID:15911620)
• results indicate that the aberrant p-JNK1/2 expression and the co-expressed p-JNK1/2 and p-p38 in breast tissues may play a role in the carcinogenesis of breast IDC (PMID:16381010)
• Data report that cepharanthine induces apoptosis in HuH-7 cells through activation of JNK1/2 and the downregulation of Akt. (PMID:16412424)
• Results showed that certain regulation involved in c-myc, c-fos, and c-jun was present in the apoptosis, and the c-Myc dependent-on and Jun N-terminal kinase (JNK) pathway also play roles. (PMID:16552729)
• JNK1 and JNK2 differentially regulate TBP through Elk-1, controlling c-Jun expression and cell proliferation (PMID:17074809)
• Human Rev7 (hRev7)/MAD2B/MAD2L2 is an interaction partner for Elk-1 and hRev7 acts to promote Elk-1 phosphorylation by the c-Jun N-terminal protein kinase (JNK) MAP kinases. (PMID:17296730)
• we defined the kinetic mechanism for the active form of JNK2alpha2. (PMID:17397142)
• Results indicate that purified JNK2 from transfected nonstressed 293T cells is a mixture of the mono-sites pThr183 and pTyr185 of its activation loop and of pThr386 along its unique C-terminal region. (PMID:17637567)
• Neutrophils from transgenic JNK2 knockout mice (which are devoid of all JNK isoforms) demonstrate a requirement for JNK2 in Toxoplasma gondii infection-induced interleukin-12p40 and CCL2/MCP-1 production. (PMID:17785791)
• JNK1/2 activity is commonly increased in head and neck squamous cell carcinoma (PMID:17908987)
• These findings suggest that JNK1 and JNK2 are involved in TNF-alpha-induced neutrophil apoptosis and GM-CSF-mediated antiapoptotic effect on neutrophils, respectively. (PMID:18439101)
• These findings are consistent with JNK2 signaling playing a protective role in acetaminophen-induced liver injury. (PMID:18586006)
• Player in triglyceride (TG) homeostasis and lipid droplet metabolism and, more specifically, in the regulation of lipolysis. (PMID:18612143)
• Results suggest that the MAP kinase insert of JNK2 plays a role in the regulation of JNK2 activation, possibly by interacting with intracellular binding partners. (PMID:18801372)
• JNK2 is linked, directly or indirectly, with SIRT1 protein stability and that this function is coupled with SIRT1 phosphorylation at serine 27. (PMID:18838864)
• JNK2 alpha2 activity is dependent on a unique mechanism of MAPK activation (PMID:18940813)
• detection of the mutation could characterize a subset of ET patients with distinct phenotype, despite its clinical significance being still undetermined (PMID:19093167)
• These results demonstrated that in A549 cells, activation of p50/p65 heterodimer through sequential activation of PKC alpha-JNK-NIK-IKK beta-NF-kappaB was required for IL-1 beta-induced uPA expression associated with migration of tumor cells. (PMID:19097143)
• important role in oxidative stress response caused by ultrafine particles from diesel vehicle engines (PMID:19154785)
• Knock-down of JNK2 unexpectedly increased the intensity of differentiation intensity in human myeloid leukemia cells. (PMID:19339050)
• Both cell protective (cell cycle progression) and destructive mechanisms (apoptosis) are simultaneously controlled by a single JNK isoform in the same cell system even under the influence of one stimulus. (PMID:19385049)
• Activation of JNK1/2 appears to be involved in serine phosphorylation of IRS1 and subsequently insulin resistance on glucose uptake, a state that can be reversed by liver X receptor agonists. (PMID:19567513)
• This study was designed to investigate the effect of c-Jun N-terminal kinase (JNK) 1 and 2 on TGF-beta(1)-regulated CTGF gene expression and corneal scar formation. (PMID:19589256)
• NAG7 plays a potential role in promoting nasopharyngeal carcinoma invasion by regulation of ERalpha and the H-ras/p-c-Raf and JNK2/AP-1/MMP1 signaling pathways. (PMID:19591174)
• Data demonstrate that hypothermia represses ischemia/reperfusion-induced endothelial cell apoptosis by inhibiting both extrinsic- and intrinsic-dependent apoptotic pathways and activation of JNK1/2. (PMID:19596001)
• The JNKs differentially regulate RNA polymerase III transcription by coordinately modulating the expression of all TFIIIB subunits. (PMID:19620725)
• regulation of p53 multimerization that requires the concerted action of JNK and Ubc13 on polysome-bound p53. (PMID:19651615)
• JNK2 suppression of a novel JNK1/c-Jun/Bcl-3 apoptotic network hasa role in basal cancer cell survival (PMID:19806201)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	mapk9	ENSDARG00000077364
mus_musculus	Mapk9	ENSMUSG00000020366
rattus_norvegicus	Mapk9	ENSRNOG00000002823
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): MAPK6 (ENSG00000069956), MOK (ENSG00000080823), NLK (ENSG00000087095), SRPK1 (ENSG00000096063), MAPK1 (ENSG00000100030), MAPK3 (ENSG00000102882), MAPK8 (ENSG00000107643), MAPK10 (ENSG00000109339), 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 9 — P45984 (reviewed: P45984)

Alternative names: JNK-55, Stress-activated protein kinase 1a, Stress-activated protein kinase JNK2, c-Jun N-terminal kinase 2

All UniProt accessions (5): D7R525, D7R528, E5RJ57, P45984, J3KNK1

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation 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 MAPK9/JNK2. In turn, MAPK9/JNK2 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. In response to oxidative or ribotoxic stresses, inhibits rRNA synthesis by phosphorylating and inactivating the RNA polymerase 1-specific transcription initiation factor RRN3. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including TP53 and YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Upon T-cell receptor (TCR) stimulation, is activated by CARMA1, BCL10, MAP2K7 and MAP3K7/TAK1 to regulate JUN protein levels. Plays an important role in the osmotic stress-induced epithelial tight-junctions disruption. When activated, promotes beta-catenin/CTNNB1 degradation and inhibits the canonical Wnt signaling pathway. Also participates in neurite growth in spiral ganglion neurons. Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the regulation of the circadian clock. Phosphorylates POU5F1, which results in the inhibition of POU5F1’s transcriptional activity and enhances its proteasomal degradation. Phosphorylates ALKBH5 in response to reactive oxygen species (ROS), promoting ALKBH5 sumoylation and inactivation. MAPK9 isoforms display different binding patterns: alpha-1 and alpha-2 preferentially bind to JUN, whereas beta-1 and beta-2 bind to ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms. JUNB is not a substrate for JNK2 alpha-2, and JUND binds only weakly to it.

Subunit / interactions. Interacts with MECOM. Interacts with DCLK2. Binds to at least four scaffolding proteins, MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP-4. These proteins also bind other components of the JNK signaling pathway. Interacts with NFATC4. Interacts with ATF7; the interaction does not phosphorylate ATF7 but acts as a docking site for ATF7-associated partners such as JUN. Interacts with BCL10. Interacts with CTNNB1 and GSK3B. Interacts with MAPKBP1. Interacts with POU5F1; phosphorylates POU5F1 at ‘Ser-355’. Found in a complex with SH3RF1, RAC2, MAP3K7/TAK1, MAP2K7/MKK7, MAPK8IP1/JIP1 and MAPK8/JNK1.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K7 and MAP2K4, which activates the enzyme. Autophosphorylated in vitro.

Activity regulation. Activated by threonine and tyrosine phosphorylation by either of two dual specificity kinases, MAP2K4 and MAP2K7. MAP2K4 shows a strong preference for Tyr-185 while MAP2K7 phosphorylates Tyr-183 preferentially. Inhibited by dual specificity phosphatases, such as DUSP1.

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 (5)

UniProt ID	Names	Canonical?
P45984-1	Alpha-2	yes
P45984-2	Alpha-1
P45984-3	Beta-1
P45984-4	Beta-2
P45984-5	5

RefSeq proteins (13): NP_001128516, NP_001295173, NP_001351536, NP_001351537, NP_001351538, NP_001351539, NP_001351540, NP_001351541, NP_001351542, NP_002743, NP_620707, NP_620708, NP_620709 (=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 (56 total): helix 18, strand 11, turn 6, sequence variant 5, splice variant 4, sequence conflict 2, binding site 2, modified residue 2, chain 1, domain 1, region of interest 1, short sequence motif 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
7N8T	X-RAY DIFFRACTION	1.69
8ELC	X-RAY DIFFRACTION	2.07
3E7O	X-RAY DIFFRACTION	2.14
7CML	X-RAY DIFFRACTION	2.15
3NPC	X-RAY DIFFRACTION	2.35

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P45984-F1	82.71	0.62

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): 151 (proton acceptor)

Ligand- & substrate-binding residues (2): 32–40; 55

Post-translational modifications (2): 183, 185

Function

Pathways and Gene Ontology

Reactome pathways

35 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-9725370	Signaling by ALK fusions and activated point mutants
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1643685	Disease
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-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-8953897	Cellular responses to stimuli

MSigDB gene sets: 451 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GOBP_CIRCADIAN_RHYTHM, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GRUETZMANN_PANCREATIC_CANCER_DN, KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, GOBP_REGULATION_OF_PODOSOME_ASSEMBLY, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, KEGG_MAPK_SIGNALING_PATHWAY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS

GO Biological Process (23): protein phosphorylation (GO:0006468), JNK cascade (GO:0007254), positive regulation of gene expression (GO:0010628), positive regulation of macrophage derived foam cell differentiation (GO:0010744), positive regulation of protein ubiquitination (GO:0031398), positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436), cellular response to reactive oxygen species (GO:0034614), Fc-epsilon receptor signaling pathway (GO:0038095), regulation of circadian rhythm (GO:0042752), response to cadmium ion (GO:0046686), rhythmic process (GO:0048511), modulation of chemical synaptic transmission (GO:0050804), protein localization to tricellular tight junction (GO:0061833), positive regulation of podosome assembly (GO:0071803), cellular senescence (GO:0090398), inflammatory response to wounding (GO:0090594), apoptotic signaling pathway (GO:0097190), positive regulation of cytokine production involved in inflammatory response (GO:1900017), positive regulation of apoptotic signaling pathway (GO:2001235), MAPK cascade (GO:0000165), cellular response to stress (GO:0033554), regulation of mRNA stability (GO:0043488), mRNA destabilization (GO:0061157)

GO Molecular Function (11): protein serine/threonine kinase activity (GO:0004674), JUN kinase activity (GO:0004705), protein serine/threonine/tyrosine kinase activity (GO:0004712), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), MAP kinase activity (GO:0004707), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), plasma membrane (GO:0005886), nuclear speck (GO:0016607), Schaffer collateral - CA1 synapse (GO:0098685)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Toll-like Receptor Cascades	6
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
Signaling by ALK in cancer	1
Toll Like Receptor TLR1:TLR2 Cascade	1
Toll Like Receptor TLR6:TLR2 Cascade	1
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	3
cellular anatomical structure	3
MAPK cascade	2
intracellular membrane-bounded organelle	2
cytoplasm	2
phosphorylation	1
protein modification process	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
macrophage derived foam cell differentiation	1
regulation of macrophage derived foam cell differentiation	1
positive regulation of cell differentiation	1
protein ubiquitination	1
regulation of protein ubiquitination	1
positive regulation of protein modification by small protein conjugation or removal	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
positive regulation of proteasomal protein catabolic process	1
positive regulation of ubiquitin-dependent protein catabolic process	1
response to reactive oxygen species	1
cellular response to oxidative stress	1
cellular response to oxygen-containing compound	1
Fc receptor signaling pathway	1
circadian rhythm	1
regulation of biological process	1
response to metal ion	1
biological_process	1
chemical synaptic transmission	1
regulation of trans-synaptic signaling	1
protein localization to cell-cell junction	1
positive regulation of protein-containing complex assembly	1
podosome assembly	1
regulation of podosome assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
cellular process	1
cellular response to stress	1
inflammatory response	1
response to wounding	1
apoptotic process	1

Protein interactions and networks

STRING

3434 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAPK9	JUN	P05412	988
MAPK9	SH3RF1	Q7Z6J0	936
MAPK9	MAPK8IP1	Q9UQF2	761
MAPK9	JUND	P17535	724
MAPK9	ATF2	P15336	723
MAPK9	POLDIP3	Q9BY77	708
MAPK9	FOS	P01100	707
MAPK9	CASP3	P42574	695
MAPK9	RRN3	Q9NYV6	673
MAPK9	IL6	P05231	669
MAPK9	NFKBIA	P25963	660
MAPK9	TNF	P01375	653
MAPK9	BCL2L11	O43521	652
MAPK9	MAPK8IP2	Q13387	622
MAPK9	INS	P01308	620

IntAct

309 interactions, top by confidence:

A	B	Type	Score
ARRB2	MAPK9	psi-mi:“MI:0915”(physical association)	0.840
MAPK9	ARRB1	psi-mi:“MI:0915”(physical association)	0.840
ARRB1	MAPK9	psi-mi:“MI:0915”(physical association)	0.840
MAPK9	ARRB2	psi-mi:“MI:0915”(physical association)	0.840
WDR62	MAPK9	psi-mi:“MI:0915”(physical association)	0.800
ATF2	MAPK9	psi-mi:“MI:0915”(physical association)	0.780
MAPK9	ATF2	psi-mi:“MI:0915”(physical association)	0.780
SHMT1	MAPK9	psi-mi:“MI:0915”(physical association)	0.780
MEOX1	MAPK9	psi-mi:“MI:0915”(physical association)	0.780
MAPK9	SF3B4	psi-mi:“MI:0915”(physical association)	0.780
EFHC2	MAPK9	psi-mi:“MI:0915”(physical association)	0.780
LNX1	MAPK9	psi-mi:“MI:0915”(physical association)	0.780
MAPK9	CEP44	psi-mi:“MI:0915”(physical association)	0.780
SF3B4	MAPK9	psi-mi:“MI:0915”(physical association)	0.780
MAPK9	EFHC2	psi-mi:“MI:0915”(physical association)	0.780
MAPK9	LNX1	psi-mi:“MI:0915”(physical association)	0.780

BioGRID (320): ATF2 (Biochemical Activity), MAPK9 (Two-hybrid), MAPK9 (Two-hybrid), MAPK9 (Two-hybrid), MAPK9 (Two-hybrid), MAPK9 (Two-hybrid), SHMT1 (Two-hybrid), SF3B4 (Two-hybrid), TEX11 (Two-hybrid), CCDC33 (Two-hybrid), EFHC2 (Two-hybrid), CEP44 (Two-hybrid), L3MBTL3 (Two-hybrid), LNX1 (Two-hybrid), C1orf94 (Two-hybrid)

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

89 interactions.

A	Effect	B	Mechanism
MAPK9	“up-regulates activity”	MAPK8IP1	phosphorylation
MAPK9	“down-regulates activity”	ATN1	phosphorylation
MAPK9	down-regulates	NFATC3	relocalization
anthra[1,9-cd]pyrazol-6(2H)-one	down-regulates	MAPK9	“chemical inhibition”
MAPK9	up-regulates	TP53	phosphorylation
MAPK9	down-regulates	NFATC2	phosphorylation
MAPK9	down-regulates	IRS1	phosphorylation
MAPK9	up-regulates	BAX
MAPK9	down-regulates	SFN	phosphorylation
MAPK9	down-regulates	YWHAZ	phosphorylation
MAPK8IP3	up-regulates	MAPK9	binding
MAPK9	up-regulates	MAPK8IP3	phosphorylation
MAPK9	down-regulates	RRN3	phosphorylation
MAPK9	“down-regulates activity”	RXRA	phosphorylation
MAPK8	up-regulates	MAPK9	phosphorylation
MAPK9	up-regulates	H2AX	phosphorylation
MAPK9	up-regulates	ATF2	phosphorylation
MAPK9	down-regulates	CDC25C	phosphorylation
MAPK9	down-regulates	STMN1	phosphorylation
MAPK9	up-regulates	CTNNB1	phosphorylation
RAC1	up-regulates	MAPK9	binding
MAPK9	down-regulates	PPM1J	phosphorylation
MAPK9	up-regulates	STAT3	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2682 predictions. Top by Δscore:

Variant	Effect	Δscore
5:180239985:TGG:T	acceptor_gain	1.0000
5:180239986:GG:G	acceptor_gain	1.0000
5:180239988:C:CC	acceptor_gain	1.0000
5:180239988:CTA:C	acceptor_loss	1.0000
5:180241025:ACTC:A	donor_loss	1.0000
5:180241027:TCACG:T	donor_loss	1.0000
5:180241028:CACGG:C	donor_loss	1.0000
5:180241029:A:AC	donor_gain	1.0000
5:180241029:ACGG:A	donor_gain	1.0000
5:180241030:C:CC	donor_gain	1.0000
5:180241030:CG:C	donor_gain	1.0000
5:180241030:CGG:C	donor_gain	1.0000
5:180241030:CGGC:C	donor_gain	1.0000
5:180241030:CGGCT:C	donor_gain	1.0000
5:180241152:CTTG:C	acceptor_gain	1.0000
5:180241154:TG:T	acceptor_gain	1.0000
5:180241154:TGCTA:T	acceptor_loss	1.0000
5:180241155:GC:G	acceptor_loss	1.0000
5:180241156:C:CA	acceptor_loss	1.0000
5:180241156:C:CC	acceptor_gain	1.0000
5:180241157:T:G	acceptor_loss	1.0000
5:180241161:G:GC	acceptor_gain	1.0000
5:180248965:ATACT:A	donor_loss	1.0000
5:180248969:TCA:T	donor_loss	1.0000
5:180248971:A:AC	donor_gain	1.0000
5:180248971:ACCGT:A	donor_loss	1.0000
5:180248972:C:CA	donor_loss	1.0000
5:180248972:C:CC	donor_gain	1.0000
5:180248972:CCGTT:C	donor_gain	1.0000
5:180249134:AAATC:A	acceptor_gain	1.0000

AlphaMissense

2802 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:180239930:A:G	W352R	1.000
5:180239930:A:T	W352R	1.000
5:180241057:A:G	W324R	1.000
5:180241057:A:T	W324R	1.000
5:180241080:A:G	L316P	1.000
5:180241084:C:G	A315P	1.000
5:180241137:A:G	L297P	1.000
5:180242665:A:T	V260D	1.000
5:180242743:C:G	W234S	1.000
5:180242744:A:G	W234R	1.000
5:180242744:A:T	W234R	1.000
5:180242746:T:G	Q233P	1.000
5:180247447:C:A	G227V	1.000
5:180247447:C:T	G227D	1.000
5:180247448:C:A	G227C	1.000
5:180247448:C:G	G227R	1.000
5:180247488:G:C	C213W	1.000
5:180247489:C:T	C213Y	1.000
5:180247490:A:G	C213R	1.000
5:180247492:C:A	G212V	1.000
5:180247492:C:T	G212D	1.000
5:180247493:C:G	G212R	1.000
5:180247500:C:A	W209C	1.000
5:180247500:C:G	W209C	1.000
5:180247502:A:G	W209R	1.000
5:180247502:A:T	W209R	1.000
5:180247507:T:A	D207V	1.000
5:180247507:T:G	D207A	1.000
5:180247508:C:A	D207Y	1.000
5:180247508:C:G	D207H	1.000

dbSNP variants (sampled 300 via entrez): RS1000016107 (5:180240174 A>T), RS1000065812 (5:180248897 A>G), RS1000085739 (5:180280541 G>A,C), RS1000130092 (5:180272553 A>C,G), RS1000197632 (5:180271278 G>A,T), RS1000326789 (5:180284782 T>C), RS1000349036 (5:180259395 G>C), RS1000359626 (5:180253964 T>C), RS1000392086 (5:180263662 T>C), RS1000406713 (5:180253683 G>C), RS1000431578 (5:180285936 C>T), RS1000691823 (5:180265423 C>T), RS1000694254 (5:180258724 C>A,T), RS1000801596 (5:180258451 A>C), RS1000824721 (5:180263306 C>T)

Disease associations

OMIM: gene MIM:602896 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006585_660	Blood protein levels	1.000000e-06
GCST90000025_513	Appendicular lean mass	1.000000e-21

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2096667 (PROTEIN FAMILY), CHEMBL3038502 (PROTEIN FAMILY), CHEMBL4179 (SINGLE PROTEIN), CHEMBL4296098 (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: 637,213 (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
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1173655	AFATINIB	4	15,144
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL189963	PALBOCICLIB	4	13,102
CHEMBL2103830	FOSTAMATINIB	4	3,841
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL3301612	ENCORAFENIB	4	4,624
CHEMBL3301622	GILTERITINIB	4	2,395
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL535	SUNITINIB	4	79,020
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL576982	QUIZARTINIB	4	4,432
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL939	GEFITINIB	4	117,814
CHEMBL941	IMATINIB	4	111,611
CHEMBL1091644	LINSITINIB	3	1,446
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL31965	CANERTINIB	3	8,083
CHEMBL603469	LESTAURTINIB	3
CHEMBL1950289	TANZISERTIB	2
CHEMBL103667	DORAMAPIMOD	2
CHEMBL1090089	PAMAPIMOD	2
CHEMBL1090090	VX-702	2
CHEMBL1189513	FURALTADONE	2
CHEMBL1230609	FORETINIB	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 (11 total), top 11:

Ligand	Action	Affinity	Parameter
JNK inhibitor VIII	Inhibition	8.4	pKi
tanzisertib	Inhibition	8.15	pIC50
pamapimod	Inhibition	7.8	pKd
JNK-IN-8	Inhibition	7.73	pIC50
RGB-286638	Inhibition	7.4	pIC50
SP600125	Inhibition	7.4	pIC50
compound 20 [PMID: 30998356]	Inhibition	7.23	pIC50
YL5084	Irreversible inhibition	7.15	pIC50
BOS172722	Inhibition	7.12	pIC50
JNK inhibitor IX	Inhibition	6.5	pIC50
compound 25c [PMID: 36649216]	Inhibition	5.03	pIC50

Binding affinities (BindingDB)

191 measured of 301 human assays (302 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
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
4-(5-{[(4-Amino-5-cyano-6-ethoxy-pyridine-2-carbonyl)-amino]-methyl}-pyridin-2-yl)-benzoic acid	IC50	4 nM
US8937068, 43	IC50	6 nM	US-8937068: Pyridopyrazine derivatives and their use
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-Amino-5-cyano-6-ethoxy-pyridine-2-carboxylic acid 2-sulfamoyl-benzylamide	IC50	12 nM
N-[4-amino-5-cyano-6-(propan-2-yloxy)pyridin-2-yl]-2-(4-methanesulfonyl-2,5-dimethoxyphenyl)acetamide	KI	18 nM
4-amino-5-cyano-6-ethoxy-N-[(4-methanesulfonylphenyl)methyl]pyridine-2-carboxamide	IC50	19 nM
(4-hydroxypiperidin-1-yl)-[4-[[4-[8-(3-methylsulfonylpropoxy)imidazo[1,2-a]pyridin-3-yl]pyrimidin-2-yl]amino]cyclohexyl]methanone	IC50	21.6 nM	US-8569306: JNK modulators
N-[4-[[4-(8-phenylmethoxyimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-yl]amino]cyclohexyl]methanesulfonamide	IC50	23.7 nM	US-8569306: JNK modulators
4-amino-5-chloro-6-ethoxy-N-[(4-methanesulfonylphenyl)methyl]pyridine-2-carboxamide	IC50	24 nM
4-amino-5-cyano-6-ethoxy-N-(pyridin-3-ylmethyl)pyridine-2-carboxamide	IC50	26 nM
4-[[4-(8-phenylmethoxyimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-yl]amino]cyclohexan-1-ol	IC50	26.9 nM	US-8569306: JNK modulators
(4-hydroxypiperidin-1-yl)-[4-[[4-(8-phenylmethoxyimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-yl]amino]cyclohexyl]methanone	IC50	33.3 nM	US-8569306: JNK modulators
N-(4-amino-5-cyano-6-ethoxypyridin-2-yl)-2-(4-acetamido-2,5-dimethoxyphenyl)acetamide	IC50	35 nM
ethyl 4-[[4-(8-phenylmethoxyimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-yl]amino]cyclohexane-1-carboxylate	IC50	48.9 nM	US-8569306: JNK modulators
N-(4-Amino-5-cyano-6-ethoxypyridin-2-yl)-2-(2,5-dimethoxyphenyl)acetamide	KI	52 nM
N-[4-[(4-imidazo[1,2-a]pyridin-3-ylpyrimidin-2-yl)amino]cyclohexyl]methanesulfonamide	IC50	56.7 nM	US-8569306: JNK modulators
N-(4-amino-5-chloro-6-ethoxypyridin-2-yl)-2-(4-methanesulfonyl-2,5-dimethoxyphenyl)acetamide	KI	61 nM
N-(4-Amino-5-cyano-6-ethoxypyridin-2-yl)-2-(2,5-dimethoxy-4-nitrophenyl)acetamide	IC50	69 nM
1-[(4-Amino-5-cyano-6-ethoxypyridin-2-ylcarbamoyl)methyl]-piperidine-4-carboxylic Acid Butylamide	IC50	69 nM
[3H-Benzothiazol-(2Z)-ylidene]-[2-(2-pyridin-3-yl-ethylamino)-pyrimidin-4-yl]-acetonitrile	IC50	70 nM
4-Amino-5-cyano-6-ethoxy-pyridine-2-carboxylic acid 2,5-dimethoxy-benzylamide	IC50	71 nM
N-(4-amino-5-cyano-6-ethoxypyridin-2-yl)-2-(4-methanesulfonyl-2,5-dimethoxyphenyl)acetamide	KI	72 nM
N-[4-Amino-5-cyano-6-(2-hydroxyethoxy)pyridin-2-yl]-2-(2,5-dimethoxyphenyl)acetamide	IC50	74 nM
4-Amino-5-chloro-6-isopropoxy-pyridine-2-carboxylic acid 4-methanesulfonyl-benzylamide	IC50	75 nM
US8937068, 25	IC50	76 nM	US-8937068: Pyridopyrazine derivatives and their use
N-(4-Amino-5-cyano-6-ethoxypyridin-2-yl)-2-(4-bromo-2,5-dimethoxyphenyl)acetamide	IC50	77 nM
1-[3-(4-chloro-2-methoxyphenyl)pyrido[2,3-b]pyrazin-6-yl]-3-ethylurea	IC50	84 nM	US-8937068: Pyridopyrazine derivatives and their use
4-[(4-imidazo[1,2-a]pyridin-3-ylpyrimidin-2-yl)amino]cyclohexan-1-ol	IC50	86.6 nM	US-8569306: JNK modulators
1-[(4-Amino-5-cyano-6-ethoxypyridin-2ylcarbamoyl)methyl]-piperidine-4-carboxylic Acid Isopropyl Amide	IC50	87 nM
US8937068, 170	IC50	103 nM	US-8937068: Pyridopyrazine derivatives and their use
1-ethyl-3-[3-(1-methylpyrazol-4-yl)pyrido[2,3-b]pyrazin-6-yl]urea	IC50	107 nM	US-8937068: Pyridopyrazine derivatives and their use
N-[4-Amino-5-cyano-6-(2-methoxyethoxy)pyridin-2-yl]-2-(2,5-dimethoxyphenyl)acetamide	IC50	110 nM
N-(4-Amino-5-cyano-6-ethoxypyridin-2-yl)-2-(2-methoxyphenyl)acetamide	IC50	120 nM
N-[4-[[4-[8-(2-hydroxypropan-2-yl)imidazo[1,2-a]pyridin-3-yl]pyrimidin-2-yl]amino]cyclohexyl]methanesulfonamide	IC50	123 nM	US-8569306: JNK modulators
3-[2-[[4-(dimethylsulfamoylamino)cyclohexyl]amino]pyrimidin-4-yl]-8-(2-hydroxypropan-2-yl)imidazo[1,2-a]pyridine	IC50	124 nM	US-8569306: JNK modulators
US8937068, 156	IC50	138 nM	US-8937068: Pyridopyrazine derivatives and their use
US8937068, 168	IC50	150 nM	US-8937068: Pyridopyrazine derivatives and their use
1-(4-hydroxybutyl)-3-(3-phenylpyrido[2,3-b]pyrazin-6-yl)urea	IC50	155 nM	US-8937068: Pyridopyrazine derivatives and their use
N-(4-Amino-5-cyano-6-ethoxypyridin-2-yl)-2-[(2-hydroxyethyl)propylamino]acetamide	IC50	160 nM
N-(4-Amino-5-cyano-6-ethoxypyridin-2-yl)-2-(4-methoxyphenyl)acetamide	IC50	180 nM
N-(4-amino-5-cyano-6-ethoxypyridin-2-yl)-2-(4-methylphenyl)acetamide	IC50	190 nM
[4-[6-(ethylcarbamoylamino)pyrido[2,3-b]pyrazin-3-yl]-2-methoxyphenyl] 4-methylbenzenesulfonate	IC50	203 nM	US-8937068: Pyridopyrazine derivatives and their use
N-(4-Amino-5-cyano-6-ethoxypyridin-2-yl)-2-(3-methoxyphenyl)acetamide	IC50	210 nM

ChEMBL bioactivities

1544 potent at pChembl≥5 of 1634 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.23	IC50	0.059	nM	CHEMBL4546504
9.62	IC50	0.24	nM	CHEMBL3220502
9.30	IC50	0.5	nM	CHEMBL3393608
9.29	IC50	0.51	nM	CHEMBL3220499
9.22	IC50	0.6	nM	CHEMBL3220496
9.17	IC50	0.68	nM	CHEMBL3220497
9.16	IC50	0.69	nM	CHEMBL3220498
9.15	IC50	0.71	nM	CHEMBL3220500
9.15	IC50	0.7	nM	CHEMBL3393607
9.00	IC50	1	nM	CHEMBL3220493
9.00	IC50	1	nM	CHEMBL3220494
9.00	IC50	1	nM	CHEMBL2216824
9.00	IC50	1	nM	CHEMBL5415466
9.00	IC50	1	nM	CHEMBL1801376
8.80	Ki	1.585	nM	CHEMBL244378
8.70	Kd	2	nM	TANZISERTIB
8.70	IC50	2	nM	CHEMBL381743
8.70	IC50	1.99	nM	CHEMBL3393607
8.70	IC50	2	nM	CHEMBL5432340
8.70	IC50	2	nM	CHEMBL3393607
8.70	IC50	2	nM	CHEMBL1801373
8.66	IC50	2.203	nM	CHEMBL5564918
8.60	IC50	2.5	nM	CHEMBL3217784
8.60	Ki	2.512	nM	CHEMBL396523
8.52	IC50	3	nM	CHEMBL3220495
8.52	IC50	3	nM	CHEMBL451523
8.50	Ki	3.162	nM	CHEMBL378627
8.40	Ki	4	nM	CHEMBL378627
8.40	Ki	4	nM	CHEMBL210618
8.40	IC50	4	nM	CHEMBL5396061
8.40	IC50	4	nM	CHEMBL5436350
8.40	IC50	4	nM	CHEMBL6172406
8.40	Ki	3.981	nM	CHEMBL210618
8.40	Ki	3.981	nM	CHEMBL377408
8.40	Ki	3.981	nM	CHEMBL243088
8.34	Kd	4.6	nM	DORAMAPIMOD
8.30	IC50	5	nM	CHEMBL245936
8.30	EC50	5	nM	JDTIC
8.30	IC50	5	nM	TANZISERTIB
8.30	IC50	5	nM	CHEMBL4878046
8.30	IC50	5	nM	CHEMBL4847078
8.30	IC50	5	nM	CHEMBL4877560
8.30	IC50	5	nM	CHEMBL5397194
8.30	IC50	5	nM	CHEMBL5410683
8.30	IC50	5	nM	CHEMBL5413843
8.30	IC50	5	nM	CHEMBL5569575
8.30	IC50	5	nM	CHEMBL97162
8.30	IC50	5	nM	CHEMBL1822146
8.30	Ki	5.012	nM	CHEMBL242865
8.25	Kd	5.6	nM	DORAMAPIMOD

PubChem BioAssay actives

1065 with measured affinity, of 3421 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
3-[4-[(2-chlorophenyl)carbamoylamino]pyrazol-1-yl]-N-(1-pyrrolidin-3-ylpyrazol-4-yl)benzamide	2091875: Inhibition of JNK2 (unknown origin) by discoverX kinomescan assay	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	1551599: Inhibition of recombinant human full length His-tagged JNK2 expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.0001	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	1189585: Inhibition of JNK2 (unknown origin) after 1 hr incubation	ic50	0.0005	uM
3-[[(E)-4-(dimethylamino)but-2-enoyl]amino]-N-[4-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]benzamide	1189585: Inhibition of JNK2 (unknown origin) after 1 hr incubation	ic50	0.0007	uM
(E)-4-(dimethylamino)-N-[4-[(3S)-3-[[4-(6-methyl-2-phenylpyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-yl]amino]pyrrolidine-1-carbonyl]phenyl]but-2-enamide	1968160: Inhibition of His-tagged human recombinant JNK2 expressed in baculovirus expression system incubated for 1 hr in presence of ATP by Z’-Lyte assay	ic50	0.0010	uM
4-(3-fluoroanilino)-5,13,16-triazatetracyclo[8.6.0.02,7.011,15]hexadeca-1(10),2,4,6,8,11(15)-hexaen-12-one	604991: Inhibition of JNK2	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	1189585: Inhibition of JNK2 (unknown origin) after 1 hr incubation	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	0.0019	uM
4-[[9-[(3S)-oxolan-3-yl]-8-(2,4,6-trifluoroanilino)purin-2-yl]amino]cyclohexan-1-ol	1425064: 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	0.0020	uM
4-[(E)-2-phenylethenyl]-5,13,16-triazatetracyclo[8.6.0.02,7.011,15]hexadeca-1,3,6,8,10,15-hexaen-12-one	604991: Inhibition of JNK2	ic50	0.0020	uM
(E)-4-(dimethylamino)-N-[4-[(3R)-3-[[4-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-yl]amino]pyrrolidine-1-carbonyl]phenyl]but-2-enamide	1968160: Inhibition of His-tagged human recombinant JNK2 expressed in baculovirus expression system incubated for 1 hr in presence of ATP by Z’-Lyte assay	ic50	0.0020	uM
1-[3-tert-butyl-1-(4-methylphenyl)pyrazol-5-yl]-3-[4-[6-(morpholin-4-ylmethyl)-3-pyridinyl]naphthalen-1-yl]urea	308415: Inhibition of Jnk2	ic50	0.0020	uM
[3-[2-[[(3R)-1-(cyclopropanecarbonyl)piperidin-3-yl]amino]pyrimidin-4-yl]-6-fluoro-2-naphthalen-2-ylbenzimidazol-5-yl] N-methylcarbamate	2091877: Inhibition of JNK2 (unknown origin) by HotSpot assay	ic50	0.0022	uM
1-[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]-3-[4-[6-(morpholin-4-ylmethyl)-3-pyridinyl]naphthalen-1-yl]urea	353511: Inhibition of JNK2alpha2 by by exchange curve binding kinetic analysis	ic50	0.0030	uM
N-(4-amino-5-cyano-6-ethoxy-2-pyridinyl)-2-(2,5-dimethoxyphenyl)acetamide	1797445: Kinase Selectivity Assay from Article 10.1021/jm060199b: “Aminopyridine-based c-Jun N-terminal kinase inhibitors with cellular activity and minimal cross-kinase activity.”	ki	0.0040	uM
N-(4-amino-5-cyano-6-propan-2-yloxy-2-pyridinyl)-2-(2,5-dimethoxy-4-methylsulfonylphenyl)acetamide	1797445: Kinase Selectivity Assay from Article 10.1021/jm060199b: “Aminopyridine-based c-Jun N-terminal kinase inhibitors with cellular activity and minimal cross-kinase activity.”	ki	0.0040	uM
(E)-4-(dimethylamino)-N-[4-[(3S)-3-[[4-[2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]pyrimidin-2-yl]amino]pyrrolidine-1-carbonyl]phenyl]but-2-enamide	1968160: Inhibition of His-tagged human recombinant JNK2 expressed in baculovirus expression system incubated for 1 hr in presence of ATP by Z’-Lyte assay	ic50	0.0040	uM
(E)-N-[4-[(3S)-3-[[4-[2-(3-chlorophenyl)pyrazolo[1,5-a]pyridin-3-yl]pyrimidin-2-yl]amino]pyrrolidine-1-carbonyl]phenyl]-4-(dimethylamino)but-2-enamide	1968160: Inhibition of His-tagged human recombinant JNK2 expressed in baculovirus expression system incubated for 1 hr in presence of ATP by Z’-Lyte assay	ic50	0.0040	uM
1-[3-tert-butyl-1-(4-methylphenyl)pyrazol-5-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	501376: Binding affinity to JNK2	kd	0.0046	uM
(E)-4-(dimethylamino)-N-[4-[(3S,4R)-3-methyl-4-[[4-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-yl]amino]pyrrolidine-1-carbonyl]phenyl]but-2-enamide	1968160: Inhibition of His-tagged human recombinant JNK2 expressed in baculovirus expression system incubated for 1 hr in presence of ATP by Z’-Lyte assay	ic50	0.0050	uM
(E)-4-(dimethylamino)-N-[4-[(3S)-3-[[4-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-yl]amino]pyrrolidine-1-carbonyl]phenyl]but-2-enamide	1968160: Inhibition of His-tagged human recombinant JNK2 expressed in baculovirus expression system incubated for 1 hr in presence of ATP by Z’-Lyte assay	ic50	0.0050	uM
(E)-4-(dimethylamino)-N-[4-[(3S)-3-[[4-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-yl]amino]piperidine-1-carbonyl]phenyl]but-2-enamide	1968160: Inhibition of His-tagged human recombinant JNK2 expressed in baculovirus expression system incubated for 1 hr in presence of ATP by Z’-Lyte assay	ic50	0.0050	uM
4-[5-(2-chloro-6-fluoroanilino)pyrazolo[3,4-b]pyridin-1-yl]-N-(oxetan-3-yl)thiophene-2-carboxamide	2091875: Inhibition of JNK2 (unknown origin) by discoverX kinomescan assay	ic50	0.0050	uM
N-ethyl-4-[[4-(2-phenyl-1H-indol-3-yl)pyrimidin-2-yl]amino]piperidine-1-carboxamide	307565: Inhibition of JNK2	ic50	0.0050	uM
N-[4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl]-2-[2-oxo-6-(trifluoromethyl)quinolin-1-yl]acetamide	617476: Inhibition of recombinant JNK2 using ser73 of c-jun as substrate preincubated for 15 mins measured after 60 mins by TR-FRET assay	ic50	0.0050	uM
4-[4-(4-fluorophenyl)-5-(2-methoxypyrimidin-4-yl)imidazol-1-yl]cyclohexan-1-ol	94574: Inhibition of JNK2-beta-2 kinase	ic50	0.0050	uM
4-anilino-2-[(4-hydroxycyclohexyl)amino]pyrimidine-5-carboxamide	1782601: Inhibition of JNK2 (unknown origin) assessed as reduction in phosphorylated ULight-labeled 4EBP1 peptide measured after 1 hr by time-resolved fluorescence assay	ic50	0.0050	uM
4-[[(1R,3S)-3-hydroxycyclohexyl]amino]-2-[(4-methoxycyclohexyl)amino]pyrimidine-5-carboxamide	1782601: Inhibition of JNK2 (unknown origin) assessed as reduction in phosphorylated ULight-labeled 4EBP1 peptide measured after 1 hr by time-resolved fluorescence assay	ic50	0.0050	uM
2-[(4-methoxycyclohexyl)amino]-4-[[(3R)-oxan-3-yl]amino]pyrimidine-5-carboxamide	1782601: Inhibition of JNK2 (unknown origin) assessed as reduction in phosphorylated ULight-labeled 4EBP1 peptide measured after 1 hr by time-resolved fluorescence assay	ic50	0.0050	uM
(3R)-7-hydroxy-N-[(2S)-1-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethylpiperidin-1-yl]-3-methylbutan-2-yl]-1,2,3,4-tetrahydroisoquinoline-3-carboxamide	381427: Increase of JNK phosphorylation in U50488 treated HEK293 cells expressing GFP tagged kappa opioid receptor	ec50	0.0050	uM
N-[3-[2-[2-ethoxy-4-(4-methylpiperazin-1-yl)anilino]-7-oxo-8-[[(2R)-oxolan-2-yl]methyl]pyrido[2,3-d]pyrimidin-6-yl]phenyl]-3-(trifluoromethyl)benzamide	1988544: Binding affinity to JNK2 (unknown origin) assessed as dissociation constant by KINOME scan assay	kd	0.0058	uM
4-[[4-[1-benzyl-5-(dimethylamino)pyrazol-4-yl]pyrimidin-2-yl]amino]cyclohexan-1-ol	473196: Inhibition of JNK2	ki	0.0060	uM
4-[[(1R,3R)-3-hydroxycyclohexyl]amino]-2-[(4-methoxycyclohexyl)amino]pyrimidine-5-carboxamide	1782601: Inhibition of JNK2 (unknown origin) assessed as reduction in phosphorylated ULight-labeled 4EBP1 peptide measured after 1 hr by time-resolved fluorescence assay	ic50	0.0060	uM
(E)-N-[4-[(3S)-3-[[4-[2-(4-chlorophenyl)pyrazolo[1,5-a]pyridin-3-yl]pyrimidin-2-yl]amino]pyrrolidine-1-carbonyl]phenyl]-4-(dimethylamino)but-2-enamide	1968160: Inhibition of His-tagged human recombinant JNK2 expressed in baculovirus expression system incubated for 1 hr in presence of ATP by Z’-Lyte assay	ic50	0.0070	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	2032527: Inhibition of JNK2 (unknown origin) incubated for 20 mins in presence of 33P-ATP	ic50	0.0076	uM
N-[4-cyano-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl]-2-(2-oxo-3,4-dihydroquinolin-1-yl)acetamide	579421: Inhibition of recombinant JNK2 after 60 mins by TR-FRET assay	ic50	0.0080	uM
N-[4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl]-2-(2-oxo-1,6-naphthyridin-1-yl)acetamide	617476: Inhibition of recombinant JNK2 using ser73 of c-jun as substrate preincubated for 15 mins measured after 60 mins by TR-FRET assay	ic50	0.0080	uM
4-[[(E)-4-(dimethylamino)but-2-enoyl]amino]-N-[3-[[4-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-yl]amino]phenyl]benzamide	1968160: Inhibition of His-tagged human recombinant JNK2 expressed in baculovirus expression system incubated for 1 hr in presence of ATP by Z’-Lyte assay	ic50	0.0083	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	2032527: Inhibition of JNK2 (unknown origin) incubated for 20 mins in presence of 33P-ATP	ic50	0.0086	uM
6-(2,4-difluorophenoxy)-8-methyl-2-(oxan-4-ylamino)pyrido[2,3-d]pyrimidin-7-one	592325: Inhibition of JNK2	kd	0.0090	uM
N-(4-amino-5-cyano-6-ethoxy-2-pyridinyl)-2-(2,5-dimethoxy-4-methylsulfonylphenyl)acetamide	1797445: Kinase Selectivity Assay from Article 10.1021/jm060199b: “Aminopyridine-based c-Jun N-terminal kinase inhibitors with cellular activity and minimal cross-kinase activity.”	ki	0.0090	uM
N-[4-chloro-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl]-2-(2-oxo-3,4-dihydroquinolin-1-yl)acetamide	579421: Inhibition of recombinant JNK2 after 60 mins by TR-FRET assay	ic50	0.0090	uM
2-N-(4-aminocyclohexyl)-9-cyclopentyl-8-N-(2,6-difluorophenyl)purine-2,8-diamine	642737: Inhibition of full length Hexa-His-tagged JNK2 using GST-tagged cJun and [gamma33P]ATP as substrate after 60 mins by scintillation counting	ic50	0.0090	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	700924: Inhibition of JNK2 in OVA-challenged and IgE-sensitized cells	ec50	0.0100	uM
N-[4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl]-2-(7-cyano-2-oxoquinolin-1-yl)acetamide	617476: Inhibition of recombinant JNK2 using ser73 of c-jun as substrate preincubated for 15 mins measured after 60 mins by TR-FRET assay	ic50	0.0100	uM
N-[4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl]-2-(6-cyano-2-oxoquinolin-1-yl)acetamide	617476: Inhibition of recombinant JNK2 using ser73 of c-jun as substrate preincubated for 15 mins measured after 60 mins by TR-FRET assay	ic50	0.0100	uM
4-[[9-cyclopentyl-8-(2-fluoroanilino)purin-2-yl]amino]cyclohexan-1-ol	642737: Inhibition of full length Hexa-His-tagged JNK2 using GST-tagged cJun and [gamma33P]ATP as substrate after 60 mins by scintillation counting	ic50	0.0100	uM
N-methyl-4-[[9-[(3S)-oxolan-3-yl]-8-(2,4,6-trifluoroanilino)purin-2-yl]amino]cyclohexane-1-carboxamide	647583: Inhibition of hexa-His-tagged JNK2 expressed in baculoviral system using GST-tagged cJun as substrate preincubated for 15 mins prior ATP addition measured after 60 mins by scintillation counting	ic50	0.0100	uM
4-[5-[[(4-amino-5-cyano-6-ethoxypyridine-2-carbonyl)amino]methyl]-2-pyridinyl]benzoic acid	1797442: ATF-2 Phosphorylation Assay from Article 10.1021/jm060465l: “Discovery of potent, highly selective, and orally bioavailable pyridine carboxamide c-Jun NH2-terminal kinase inhibitors.”	ic50	0.0110	uM
4-[3-(2-morpholin-4-ylethoxy)phenyl]-5,13,16-triazatetracyclo[8.6.0.02,7.011,15]hexadeca-1(10),2,4,6,8,11(15)-hexaen-12-one	604991: Inhibition of JNK2	ic50	0.0110	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
pyrazolanthrone	increases activity, decreases phosphorylation, increases reaction, decreases activity, decreases reaction (+2 more)	20
Acetylcysteine	increases activity, increases phosphorylation, increases abundance, decreases phosphorylation, affects cotreatment (+1 more)	13
sodium arsenite	affects cotreatment, decreases expression, affects binding, increases reaction, increases activity (+2 more)	10
Tetradecanoylphorbol Acetate	increases phosphorylation, increases reaction, decreases reaction	9
Arsenic Trioxide	affects expression, decreases reaction, increases phosphorylation, increases activity, increases expression (+3 more)	8
Quercetin	affects cotreatment, increases expression, decreases reaction, increases phosphorylation	8
Lipopolysaccharides	decreases reaction, increases phosphorylation, increases abundance, decreases expression, decreases phosphorylation (+2 more)	7
Doxorubicin	decreases reaction, increases phosphorylation, affects cotreatment, decreases expression, increases activity	6
Hydrogen Peroxide	increases phosphorylation, decreases expression, increases reaction, decreases reaction	6
Cadmium Chloride	increases activity, increases phosphorylation, increases expression, affects cotreatment, decreases expression (+1 more)	5
Particulate Matter	increases expression, increases phosphorylation, increases reaction, affects cotreatment	5
deoxynivalenol	decreases activity, increases expression, increases activity, increases phosphorylation	4
Resveratrol	increases expression, decreases reaction, increases phosphorylation, decreases phosphorylation, increases activity (+1 more)	4
Capsaicin	decreases reaction, increases phosphorylation, increases activity	4
Paraquat	increases expression, increases activity, decreases reaction, increases phosphorylation	4
Silicon Dioxide	decreases reaction, increases phosphorylation	4
diphenyleneiodonium	decreases reaction, increases phosphorylation, increases abundance	3
acetovanillone	decreases reaction, increases phosphorylation, increases abundance	3
Bortezomib	affects cotreatment, affects expression, increases phosphorylation, increases reaction, increases response to substance	3
Cadmium	decreases reaction, increases phosphorylation, affects response to substance	3
Valproic Acid	increases expression	3
sanguinarine	decreases reaction, increases phosphorylation, affects cotreatment	2
bisphenol A	increases expression, increases phosphorylation	2
sulforaphane	decreases reaction, increases phosphorylation, affects cotreatment, increases reaction	2
cobaltous chloride	decreases reaction, increases phosphorylation	2
manganese chloride	increases phosphorylation, increases activity	2
nickel sulfate	increases phosphorylation	2
arsenic trichloride	increases phosphorylation, decreases reaction, increases expression	2
1,2-bis(2-aminophenoxy)ethane N,N,N’,N’-tetraacetic acid acetoxymethyl ester	decreases reaction, increases activity, increases phosphorylation, increases expression	2
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases phosphorylation	2

ChEMBL screening assays

935 unique, capped per target: 922 binding, 11 functional, 2 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
CHEMBL4424887	ADMET	Inhibition of full-length human N-terminal His-tagged JNK2alpha2 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

4 cell lines: 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3AS	Abcam HEK293T MAPK9 KO	Transformed cell line	Female
CVCL_D7UQ	Ubigene A-549 MAPK9 KO	Cancer cell line	Male
CVCL_E0HJ	Ubigene HeLa MAPK9 KO	Cancer cell line	Female
CVCL_SX01	HAP1 MAPK9 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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