MAPK1

Summary

MAPK1 (mitogen-activated protein kinase 1, HGNC:6871) is a protein-coding gene on chromosome 22q11.22, encoding Mitogen-activated protein kinase 1 (P28482). Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. In precision oncology, MAPK1 E322K confers sensitivity to Erlotinib in Head And Neck Squamous Cell Carcinoma (CIViC Level C); 1 further curated variant–drug associations are listed below. It is a selective cancer dependency (DepMap: 11.3% of cell lines).

This gene encodes a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), 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. The activation of this kinase requires its phosphorylation by upstream kinases. Upon activation, this kinase translocates to the nucleus of the stimulated cells, where it phosphorylates nuclear targets. One study also suggests that this protein acts as a transcriptional repressor independent of its kinase activity. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Two alternatively spliced transcript variants encoding the same protein, but differing in the UTRs, have been reported for this gene.

Source: NCBI Gene 5594 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Noonan syndrome 13 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 8
• Clinical variants (ClinVar): 82 total — 5 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 120
• Druggable target: yes — 324 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 2 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 4 cancer types
• Cancer dependency (DepMap): dependent in 11.3% of screened cell lines
• MANE Select transcript: NM_002745

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6871
Approved symbol	MAPK1
Name	mitogen-activated protein kinase 1
Location	22q11.22
Locus type	gene with protein product
Status	Approved
Aliases	ERK, ERK2, p41mapk, MAPK2
Ensembl gene	ENSG00000100030
Ensembl biotype	protein_coding
OMIM	176948
Entrez	5594

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000215832, ENST00000398822, ENST00000491588, ENST00000544786, ENST00000879585, ENST00000879586, ENST00000879587, ENST00000962868, ENST00000962869, ENST00000962870, ENST00000962871, ENST00000962872

RefSeq mRNA: 2 — MANE Select: NM_002745 NM_002745, NM_138957

CCDS: CCDS13795

Canonical transcript exons

ENST00000215832 — 9 exons

Exon	Start	End
ENSE00000651101	21772873	21772982
ENSE00000651102	21788257	21788388
ENSE00000879357	21799012	21799128
ENSE00000879358	21805850	21806039
ENSE00000879359	21807664	21807846
ENSE00001135958	21769195	21769320
ENSE00001650159	21788694	21788808
ENSE00001838512	21867322	21867645
ENSE00001857706	21759657	21764240

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 99.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 64.9575 / max 788.3649, expressed in 1827 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193251	64.1789	1827
193250	0.5751	273
193242	0.1729	44
193252	0.0307	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	99.53	gold quality
postcentral gyrus	UBERON:0002581	99.28	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.26	gold quality
parietal lobe	UBERON:0001872	99.06	gold quality
entorhinal cortex	UBERON:0002728	99.04	gold quality
superior frontal gyrus	UBERON:0002661	98.62	gold quality
lateral globus pallidus	UBERON:0002476	98.57	gold quality
pons	UBERON:0000988	97.99	gold quality
visceral pleura	UBERON:0002401	97.98	gold quality
upper leg skin	UBERON:0004262	97.91	gold quality
skin of hip	UBERON:0001554	97.82	gold quality
superior vestibular nucleus	UBERON:0007227	97.69	gold quality
subthalamic nucleus	UBERON:0001906	97.67	gold quality
lower lobe of lung	UBERON:0008949	97.59	gold quality
substantia nigra pars compacta	UBERON:0001965	97.46	gold quality
urethra	UBERON:0000057	97.44	gold quality
mammalian vulva	UBERON:0000997	97.36	gold quality
cauda epididymis	UBERON:0004360	97.35	gold quality
esophagus squamous epithelium	UBERON:0006920	97.34	gold quality
nucleus accumbens	UBERON:0001882	97.28	gold quality
adult organism	UBERON:0007023	97.27	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.17	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.16	gold quality
bronchial epithelial cell	CL:0002328	97.15	gold quality
trigeminal ganglion	UBERON:0001675	97.13	gold quality
temporal lobe	UBERON:0001871	97.11	gold quality
caput epididymis	UBERON:0004358	97.08	gold quality
corpus epididymis	UBERON:0004359	97.04	gold quality
parietal pleura	UBERON:0002400	97.03	gold quality
trabecular bone tissue	UBERON:0002483	97.02	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-CURD-46	yes	20.00
E-CURD-88	yes	18.46
E-HCAD-9	yes	18.22
E-ANND-3	yes	11.24
E-GEOD-135922	yes	6.39

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
SULT1A1	Activation
SULT1A3	Activation

Upstream regulators (CollecTRI, top): AR, ATF3, BCL6, CEBPA, CEBPB, DLL4, DNMT1, E2F1, EGR4, EHF, ELF1, ELF4, ESR1, ETS2, EZH2, GATA6, GFI1, HES1, HESX1, HIF1A, HNF4A, ID1, ID3, IER2, IRF3, IRF6, IRF8, JUND, KLF5, LITAF, MAFB, MAX, MEF2C, MITF, MSC, MYC, MYF6, MYOD1, NCOA1, NFATC1

miRNA regulators (miRDB)

299 targeting MAPK1, 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-3163	100.00	77.23	8605
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-5696	99.98	72.36	4487

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 11.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• MEK1 interacts with and phosphorylates ERK2. This interaction is mediated via a conserved N-terminal docking site in MEK1. Note that this interaction was demonstrated using rat ERK2. (PMID:11134045)
• MEK2 interacts with ERK2. This interaction is mediated via a conserved N-terminal docking site in MEK2. Note that this interaction was demonstrated using rat ERK2. (PMID:11134045)
• Angiogenin induces transient phosphorylation of extracellular signal-related kinase 1/2 (Erk1/2) in cultured human umbilical vein endothelial cells. (PMID:11549292)
• Unregulated activation of STAT-5, ERK1/2 and c-Fos may contribute to the phenotypic transformation from myelodysplastic syndrome to acute leukaemia. Impaired ERK1/2 signalling pathways were activated only by GM-CSF but not by Epo. (PMID:11583024)
• C-terminal halves of ERK2 and ERK3DeltaC are primarily responsible for subcellular localization in resting cells; and the N-terminal folding domain of ERK2 is required for its activation in cells, interaction with MEK1, and accumulation in the nucleus (PMID:11741894)
• suggests that upon activation Ras becomes associated with IRAK, Traf-6, and TAK-1, possibly aiding the assembly of this multiprotein signaling complex required for p38 MAPK activation by IL-1 (PMID:11744690)
• Based on a MEK1-derived peptide, we developed inhibitors of ERK activation in vitro and in vivo. (PMID:11756441)
• Extracellular signal-regulated kinase (ERK1 and ERK2) activation is required for GP Ibalpha-dependent endothelial cell migration. (PMID:11776327)
• residues located at different positions are important for discriminating between ERK and p38 MAPKs (PMID:11786537)
• Cooperativity between the Ras-ERK and Rho-Rho kinase pathways in urokinase-type plasminogen activator-stimulated cell migration (PMID:11805108)
• ERK and p38 MAP kinase pathways cooperate in mediating cytokine-induced proliferation of OCI-AML5 cell line (PMID:11840291)
• mediates regulation of p73 by c-Abl (PMID:11840343)
• ERK1/2 activation is a regulator of progesterone synthesis in hGL cells (PMID:11861509)
• p42/44MAPK regulates baseline permeability and cGMP-induced hyperpermeability in endothelial cells (PMID:11866540)
• Glucocorticoids synergistically enhance nontypeable Haemophilus influenzae-induced Toll-like receptor 2 expression via a negative cross-talk with p38 MAP kinase. (PMID:11867630)
• Hepatitis C virus core protein expression activates extracellular signal-regulated kinase (ERK) (PMID:11878930)
• role of activation in TFF-peptide-stimulated bronchial epithelial cell migration and tumor necrosis factor-alpha-induced interleukin-6 and IL-8 secretion (PMID:11884401)
• ML-1-induced IL-6 and IL-8 production is mediated through the activation of ERK1/2 (PMID:11891214)
• ERK negatively regulates the epidermal growth factor-mediated interaction of Gab1 and the phosphatidylinositol 3-kinase (PMID:11896055)
• The functional role of mitogen-activated protein kinase (MAPK) signaling and c-Jun induction in phorbol 12-myristate 13-acetate (PMA)-induced human 12(S)-lipoxygenase gene expression (PMID:11914583)
• role of activation in IGFBP-5 stimulation of growth and IGF-I secretion in intestinal smooth muscle (PMID:11923300)
• Activation of p38 MAP-kinase and caldesmon phosphorylation are essential for urokinase-induced human smooth muscle cell migration. (PMID:11930938)
• Activation of the p42 MAPK pathway contributes to the underlying mechanism of IL-12 suppression by soluble CD40 ligand. (PMID:11937531)
• mediates activation of neutrophils by lipopolysaccharide (PMID:11943771)
• Down-regulation of ERK1 and ERK2 activity during differentiation of the intestinal cell line HT-29. (PMID:11952164)
• Mechanism of 17-beta-estradiol-induced Erk1/2 activation in breast cancer cells. A role for HER2 AND PKC-delta (PMID:11960991)
• eNOS expression might be regulated by PI-3K and the ERK1/2 signaling pathway (PMID:11961297)
• Results show that oncogenic ras provokes premature senescence by sequentially activating the MEK-ERK and MKK3/6-p38 pathways in normal, primary cells. (PMID:11971971)
• Eicosapentaenoic acid and docosahexaenoic acid modulate MAP kinase enzyme activity in human T-cells (PMID:12030372)
• ERK2 activity and dual-phosphorylation were undetectable in expanding and self-renewing hematopoietic progenitors (HP). Adding IL-3, inducing maturation and cell death in HP, led to sustained high levels of ERK2 activity and dual-phosphorylation. (PMID:12032872)
• The signaling pathway triggered by both 8-iso-PGFalpha and low concentrations of U46619 to induce platelet adhesion and shape change implicates Syk, the p38 MAP kinase, and actin polymerization. (PMID:12038794)
• role in stabilizing p21(Cip1) by phosphorylation (PMID:12058028)
• p38MAPK is activated by phosphorylated ATF6 and induces HSPA5 binding (PMID:12076252)
• NBMPR-sensitive equilibrative nucleoside transporters are targets for p38 MAPK inhibitors (PMID:12077112)
• the NOx-induced cell proliferation via activation of p38 might contribute to lung tissue damage caused by NOx (PMID:12079429)
• Provant Wound Closure System induces activation of p44/42 MAP kinase in normal cultured human fibroblasts (PMID:12081892)
• p38 MAP kinase regulation of AP-2 binding in TGF-beta1-stimulated chondrogenesis of human trabecular bone-derived cells (PMID:12081893)
• ERK activation by cAMP does not require RAP1 (PMID:12082090)
• Formation of an hER alpha-COUP-TFI complex enhances hER alpha AF-1 through Ser118 phosphorylation by ERK2. (PMID:12093745)
• p38 MAP kinase activation appears to be an important upstream signaling event associated with increased endothelial permeability and vascular endothelial cadherin redistribution (PMID:12095140)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mapk1	ENSDARG00000027552
mus_musculus	Mapk1	ENSMUSG00000063358
rattus_norvegicus	Mapk1	ENSRNOG00000001849
drosophila_melanogaster	rl	FBGN0003256
caenorhabditis_elegans		WBGENE00003401

Paralogs (19): MAPK9 (ENSG00000050748), MAPK6 (ENSG00000069956), MOK (ENSG00000080823), NLK (ENSG00000087095), SRPK1 (ENSG00000096063), 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 1 — P28482 (reviewed: P28482)

Alternative names: ERT1, Extracellular signal-regulated kinase 2, MAP kinase isoform p42, Mitogen-activated protein kinase 2

All UniProt accessions (2): P28482, Q1HBJ4

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade also plays a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1 and FXR1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. Mediates phosphorylation of TPR in response to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation. Phosphorylates CDK2AP2. Phosphorylates phosphoglycerate kinase PGK1 under hypoxic conditions to promote its targeting to the mitochondrion and suppress the formation of acetyl-coenzyme A from pyruvate. Phosphorylates GJA1 at ‘Ser-279’ and ‘Ser-282’ resulting in an increase in GJA1 ubiquitination and ultimately lysosomal degradation. Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity.

Subunit / interactions. Binds both upstream activators and downstream substrates in multimolecular complexes. This interaction inhibits its tyrosine-kinase activity. Interacts with ADAM15, ARHGEF2, ARRB2, DAPK1 (via death domain), HSF4, IER3, IPO7, NISCH, SGK1, and isoform 1 of NEK2. Interacts (via phosphorylated form) with TPR (via C-terminal region and phosphorylated form); the interaction requires dimerization of MAPK1/ERK2 and increases following EGF stimulation. Interacts with MAP2K1. Interacts with DUSP6. Interacts (phosphorylated form) with CAV2 (‘Tyr-19’-phosphorylated form); the interaction, promoted by insulin, leads to nuclear location and MAPK1 activation. Interacts with MORG1, PEA15 and MKNK2. MKNK2 isoform 1 binding prevents from dephosphorylation and inactivation. Interacts with DCC. The phosphorylated form interacts with PML (isoform PML-4). Interacts with STYX. Interacts with CDK2AP2. Interacts with CAVIN4. Interacts with DUSP7; the interaction enhances DUSP7 phosphatase activity. Interacts with GIT1; this interaction is necessary for MAPK1 localization to focal adhesions. Interacts with ZNF263. Interacts with phosphoglycerate kinase PGK1; the interaction is direct, occurs under hypoxic conditions, and promotes interaction between PGK1 and PIN1. (Microbial infection) Interacts with HIV-1 Nef through its SH3 domain.

Subcellular location. Cytoplasm. Cytoskeleton. Spindle. Nucleus. Microtubule organizing center. Centrosome. Membrane. Caveola. Cell junction. Focal adhesion.

Post-translational modifications. Phosphorylated upon KIT and FLT3 signaling. Dually phosphorylated on Thr-185 and Tyr-187, which activates the enzyme. Undergoes regulatory phosphorylation on additional residues such as Ser-246 and Ser-248 in the kinase insert domain (KID) These phosphorylations, which are probably mediated by more than one kinase, are important for binding of MAPK1/ERK2 to importin-7 (IPO7) and its nuclear translocation. In addition, autophosphorylation of Thr-190 was shown to affect the subcellular localization of MAPK1/ERK2 as well. Ligand-activated ALK induces tyrosine phosphorylation. Dephosphorylated by PTPRJ at Tyr-187. Phosphorylation on Ser-29 by SGK1 results in its activation by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. DUSP3 and DUSP6 dephosphorylate specifically MAPK1/ERK2 and MAPK3/ERK1 whereas DUSP9 dephosphorylates a broader range of MAPKs. Dephosphorylated by DUSP1 and DUSP2 at Thr-185 and Tyr-187. ISGylated. Ubiquitinated by TRIM15 via ‘Lys-63’-linked ubiquitination; leading to activation. Deubiquitinated by CYLD.

Disease relevance. Noonan syndrome 13 (NS13) [MIM:619087] A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells. NS13 inheritance is autosomal dominant. There is considerable variability in severity. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-185 and Tyr-187 in response to external stimuli like insulin or NGF. Both phosphorylations are required for activity. This phosphorylation causes dramatic conformational changes, which enable full activation and interaction of MAPK1/ERK2 with its substrates. Phosphorylation on Ser-29 by SGK1 results in its activation by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. Dephosphorylated and inactivated by DUSP1, DUSP3, DUSP6 and DUSP9. Inactivated by pyrimidylpyrrole inhibitors.

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 (2)

UniProt ID	Names	Canonical?
P28482-1	1	yes
P28482-2	2

RefSeq proteins (2): NP_002736, NP_620407 (=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
IPR008349	MAPK_ERK1/2	Family
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
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 (79 total): helix 22, strand 15, modified residue 8, mutagenesis site 8, sequence variant 7, turn 7, short sequence motif 3, binding site 2, initiator methionine 1, chain 1, splice variant 1, domain 1, DNA-binding region 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

160 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8AOJ	X-RAY DIFFRACTION	1.12
4ZZN	X-RAY DIFFRACTION	1.33
6SLG	X-RAY DIFFRACTION	1.33
5WP1	X-RAY DIFFRACTION	1.4
4QTA	X-RAY DIFFRACTION	1.45
4QTE	X-RAY DIFFRACTION	1.5
2Y9Q	X-RAY DIFFRACTION	1.55
6QA3	X-RAY DIFFRACTION	1.57
6QAL	X-RAY DIFFRACTION	1.57
6GJD	X-RAY DIFFRACTION	1.58
6QA1	X-RAY DIFFRACTION	1.58
6QAH	X-RAY DIFFRACTION	1.58
6QAQ	X-RAY DIFFRACTION	1.58
3SA0	X-RAY DIFFRACTION	1.59
8AO5	X-RAY DIFFRACTION	1.59
6Q7T	X-RAY DIFFRACTION	1.6
6QA4	X-RAY DIFFRACTION	1.6
8AOH	X-RAY DIFFRACTION	1.6
8AOI	X-RAY DIFFRACTION	1.6
8AOG	X-RAY DIFFRACTION	1.6
8AO7	X-RAY DIFFRACTION	1.61
8AOF	X-RAY DIFFRACTION	1.61
8AOA	X-RAY DIFFRACTION	1.62
8AOC	X-RAY DIFFRACTION	1.62
8AOD	X-RAY DIFFRACTION	1.62
8AOB	X-RAY DIFFRACTION	1.62
8AO9	X-RAY DIFFRACTION	1.62
7NR8	X-RAY DIFFRACTION	1.63
4ZZO	X-RAY DIFFRACTION	1.63
8PT0	X-RAY DIFFRACTION	1.65

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P28482-F1	90.99	0.79

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): 149 (proton acceptor)

Ligand- & substrate-binding residues (2): 31–39; 54

Post-translational modifications (8): 2, 29, 185, 187, 190, 246, 248, 284

Mutagenesis-validated functional residues (8):

Position	Phenotype
54	does not inhibit interaction with map2k1.
176–179	inhibits homodimerization and interaction with tpr.
185	inhibits interaction with tpr; when associated with a-187.
187	inhibits interaction with tpr; when associated with a-185.
234	inhibits interaction with tpr.
318	loss of dephosphorylation by ptprj.
318	inhibits interaction with map2k1 but not with tpr; when associated with n-321.
321	inhibits interaction with map2k1 but not with tpr; when associated with n-318.

Function

Pathways and Gene Ontology

Reactome pathways

172 pathways

ID	Pathway
R-HSA-111995	phospho-PLA2 pathway
R-HSA-112409	RAF-independent MAPK1/3 activation
R-HSA-112411	MAPK1 (ERK2) activation
R-HSA-1181150	Signaling by NODAL
R-HSA-1295596	Spry regulation of FGF signaling
R-HSA-1502540	Signaling by Activin
R-HSA-162658	Golgi Cisternae Pericentriolar Stack Reorganization
R-HSA-170968	Frs2-mediated activation
R-HSA-198753	ERK/MAPK targets
R-HSA-202670	ERKs are inactivated
R-HSA-2029482	Regulation of actin dynamics for phagocytic cup formation
R-HSA-2173795	Downregulation of SMAD2/3:SMAD4 transcriptional activity
R-HSA-2173796	SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription
R-HSA-2559580	Oxidative Stress Induced Senescence
R-HSA-2559582	Senescence-Associated Secretory Phenotype (SASP)
R-HSA-2559585	Oncogene Induced Senescence
R-HSA-2871796	FCERI mediated MAPK activation
R-HSA-3371453	Regulation of HSF1-mediated heat shock response
R-HSA-375165	NCAM signaling for neurite out-growth
R-HSA-437239	Recycling pathway of L1
R-HSA-444257	RSK activation
R-HSA-445144	Signal transduction by L1
R-HSA-450341	Activation of the AP-1 family of transcription factors
R-HSA-456926	Thrombin signalling through proteinase activated receptors (PARs)
R-HSA-5654726	Negative regulation of FGFR1 signaling
R-HSA-5654727	Negative regulation of FGFR2 signaling
R-HSA-5654732	Negative regulation of FGFR3 signaling
R-HSA-5654733	Negative regulation of FGFR4 signaling
R-HSA-5663213	RHO GTPases Activate WASPs and WAVEs
R-HSA-5668599	RHO GTPases Activate NADPH Oxidases

MSigDB gene sets: 1371 (showing top): PID_BCR_5PATHWAY, GOBP_REGULATION_OF_GOLGI_ORGANIZATION, GOBP_CHROMOSOME_ORGANIZATION, BIOCARTA_PTEN_PATHWAY, GOBP_LABYRINTHINE_LAYER_DEVELOPMENT, ELVIDGE_HYPOXIA_DN, REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, BIOCARTA_FMLP_PATHWAY, PID_S1P_S1P1_PATHWAY, REACTOME_INNATE_IMMUNE_SYSTEM

GO Biological Process (62): MAPK cascade (GO:0000165), protein phosphorylation (GO:0006468), apoptotic process (GO:0006915), chemotaxis (GO:0006935), DNA damage response (GO:0006974), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), epidermal growth factor receptor signaling pathway (GO:0007173), chemical synaptic transmission (GO:0007268), learning or memory (GO:0007611), insulin receptor signaling pathway (GO:0008286), positive regulation of macrophage chemotaxis (GO:0010759), positive regulation of peptidyl-threonine phosphorylation (GO:0010800), Schwann cell development (GO:0014044), cytosine metabolic process (GO:0019858), regulation of ossification (GO:0030278), obsolete regulation of cellular pH (GO:0030641), thyroid gland development (GO:0030878), lipopolysaccharide-mediated signaling pathway (GO:0031663), positive regulation of telomere maintenance (GO:0032206), regulation of stress-activated MAPK cascade (GO:0032872), mammary gland epithelial cell proliferation (GO:0033598), cellular response to amino acid starvation (GO:0034198), response to nicotine (GO:0035094), intracellular signal transduction (GO:0035556), ERBB signaling pathway (GO:0038127), ERBB2-ERBB3 signaling pathway (GO:0038133), outer ear morphogenesis (GO:0042473), myelination (GO:0042552), response to exogenous dsRNA (GO:0043330), positive regulation of cholesterol biosynthetic process (GO:0045542), negative regulation of cell differentiation (GO:0045596), insulin-like growth factor receptor signaling pathway (GO:0048009), thymus development (GO:0048538), T cell receptor signaling pathway (GO:0050852), B cell receptor signaling pathway (GO:0050853), stress-activated MAPK cascade (GO:0051403), regulation of cytoskeleton organization (GO:0051493), Bergmann glial cell differentiation (GO:0060020), long-term synaptic potentiation (GO:0060291)

GO Molecular Function (14): phosphotyrosine residue binding (GO:0001784), DNA binding (GO:0003677), protein serine/threonine kinase activity (GO:0004674), MAP kinase activity (GO:0004707), ATP binding (GO:0005524), RNA polymerase II CTD heptapeptide repeat kinase activity (GO:0008353), phosphatase binding (GO:0019902), identical protein binding (GO:0042802), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (27): extracellular region (GO:0005576), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), early endosome (GO:0005769), late endosome (GO:0005770), endoplasmic reticulum lumen (GO:0005788), Golgi apparatus (GO:0005794), centrosome (GO:0005813), cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), caveola (GO:0005901), focal adhesion (GO:0005925), cilium (GO:0005929), microtubule cytoskeleton (GO:0015630), pseudopodium (GO:0031143), azurophil granule lumen (GO:0035578), ciliary basal body (GO:0036064), synapse (GO:0045202), mitotic spindle (GO:0072686), ciliary tip (GO:0097542), ficolin-1-rich granule lumen (GO:1904813), spindle (GO:0005819), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-21 pathways:

Category	Pathways
Cellular Senescence	3
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	2
Ca-dependent events	1
MAPK1/MAPK3 signaling	1
RAF-independent MAPK1/3 activation	1
Developmental Biology	1
Negative regulation of FGFR1 signaling	1
Negative regulation of FGFR2 signaling	1
Negative regulation of FGFR3 signaling	1
Negative regulation of FGFR4 signaling	1
Signaling by TGFB family members	1
Mitotic Prophase	1
Prolonged ERK activation events	1
Nuclear Events (kinase and transcription factor activation)	1
MAPK targets/ Nuclear events mediated by MAP kinases	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular membrane-bounded organelle	3
cytoplasm	3
protein kinase activity	2
protein serine/threonine kinase activity	2
endosome	2
microtubule organizing center	2
plasma membrane bounded cell projection	2
intracellular signaling cassette	1
phosphorylation	1
protein modification process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
response to chemical	1
taxis	1
cellular response to stress	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
signal transduction	1
ERBB signaling pathway	1
anterograde trans-synaptic signaling	1
behavior	1
cognition	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to insulin stimulus	1
positive regulation of leukocyte chemotaxis	1
regulation of macrophage chemotaxis	1
macrophage chemotaxis	1
regulation of granulocyte chemotaxis	1
positive regulation of macrophage migration	1
positive regulation of protein phosphorylation	1
regulation of peptidyl-threonine phosphorylation	1
peptidyl-threonine phosphorylation	1
Schwann cell differentiation	1
glial cell development	1
pyrimidine nucleobase metabolic process	1

Protein interactions and networks

STRING

6760 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAPK1	JUN	P05412	958
MAPK1	STAT3	P40763	951
MAPK1	MAP2K1	Q02750	950
MAPK1	DUSP6	Q16828	928
MAPK1	PTPN7	P35236	919
MAPK1	TP53	P04637	912
MAPK1	IL6	P05231	897
MAPK1	HSP90AA1	P07900	897
MAPK1	AKT1	P31749	872
MAPK1	GRB2	P29354	866
MAPK1	FOS	P01100	864
MAPK1	MAP2K2	P36507	856
MAPK1	ARRB1	P49407	856
MAPK1	IQGAP1	P46940	842
MAPK1	RPS6KA1	Q15418	821

IntAct

380 interactions, top by confidence:

A	B	Type	Score
RPS6KA2	MAPK1	psi-mi:“MI:0914”(association)	0.910
MAPK1	RPS6KA2	psi-mi:“MI:0915”(physical association)	0.910
MAPK1	RPS6KA1	psi-mi:“MI:2364”(proximity)	0.900
MAPK1	PEA15	psi-mi:“MI:0915”(physical association)	0.900
MAPK1	RPS6KA1	psi-mi:“MI:0915”(physical association)	0.900
PEA15	MAPK1	psi-mi:“MI:0407”(direct interaction)	0.900
RPS6KA1	MAPK1	psi-mi:“MI:0407”(direct interaction)	0.900
MAPK1	MKNK1	psi-mi:“MI:0915”(physical association)	0.820
MAPK1	DUSP4	psi-mi:“MI:0915”(physical association)	0.810
DUSP4	MAPK1	psi-mi:“MI:0914”(association)	0.810
PTPN7	MAPK1	psi-mi:“MI:0915”(physical association)	0.770
MAPK1	DUSP6	psi-mi:“MI:0915”(physical association)	0.760
DUSP6	MAPK3	psi-mi:“MI:0914”(association)	0.740
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
DCC	NTN1	psi-mi:“MI:0914”(association)	0.700
ARHGEF26	CASK	psi-mi:“MI:0914”(association)	0.690
spvC	MAPK1	psi-mi:“MI:0203”(dephosphorylation reaction)	0.680
spvC	MAPK1	psi-mi:“MI:0407”(direct interaction)	0.680
PTPDC1	MAPK1	psi-mi:“MI:0915”(physical association)	0.670
MAPK1	LZTS2	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (863): MAPK1 (Biochemical Activity), MAPK1 (Affinity Capture-Western), MAPK1 (Affinity Capture-Western), MAPK1 (Biochemical Activity), MAPK1 (Affinity Capture-Western), RAF1 (Affinity Capture-Western), MAP2K1 (Affinity Capture-Western), MAPK3 (Affinity Capture-Western), Eif4ebp1 (Biochemical Activity), MAPK1 (Affinity Capture-Western), ATF2 (Biochemical Activity), Eif4ebp1 (Biochemical Activity), ZC3HC1 (Biochemical Activity), MAPK1 (Biochemical Activity), HIF1A (Biochemical Activity)

ESM2 similar proteins: A0A5B9GBF0, A1CPG7, A1D2C9, A1IVT7, A2BD05, A2QRF6, B0XR80, D3ZBE5, G1XJZ4, G5EDF7, G5EFM9, M1T7M3, O09110, O75716, O88697, P0CP69, P21708, P26696, P27361, P28482, P45985, P46196, P46734, P47809, P52564, P57760, P59895, P70236, Q0D0P5, Q0U4L8, Q1DUU8, Q1KTF2, Q2WFL5, Q4PC06, Q4W6D3, Q4WSF6, Q52PH6, Q56R42, Q5E9X2, Q63844

Diamond homologs: A0A194WDG1, A0A1S3Z5Y0, A1CPG7, A1D2C9, A2QRF6, A2XFC8, A5PKJ4, A9S9Q8, A9T142, B0XR80, B0Y4X4, B0Y8W7, C4YGK0, G4N0Z0, G4N374, O13352, O23236, O42781, O61443, O94737, P0C865, P0CP66, P0CP67, P0CP68, P0CP69, P14681, P16892, P21708, P26696, P27361, P27638, P28482, P36005, P39745, P40417, P42525, P43068, P46196, P47811, P47812

SIGNOR signaling

200 interactions.

A	Effect	B	Mechanism
PTPRJ	“down-regulates activity”	MAPK1	dephosphorylation
PTPRJ	down-regulates	MAPK1	dephosphorylation
MAPK1	“down-regulates activity”	CASP9	phosphorylation
MAPK1	up-regulates	SMAD4	phosphorylation
MAPK1	“down-regulates activity”	THRB	phosphorylation
MAPK1	“up-regulates activity”	RPS6KA1	phosphorylation
DUSP6	down-regulates	MAPK1	dephosphorylation
PPP1CA	down-regulates	MAPK1	dephosphorylation
PPP2CA	“down-regulates activity”	MAPK1	dephosphorylation
MAPK1	“up-regulates activity”	MAFA	phosphorylation
PEA15	down-regulates	MAPK1
MAPK1	up-regulates	RPS6KB1	phosphorylation
MAPK1	“down-regulates quantity by destabilization”	PPARG	phosphorylation
MAPK1	down-regulates	UBTF	phosphorylation
MAPK1	down-regulates	ESPL1	phosphorylation
MAPK1	down-regulates	EIF4EBP1	phosphorylation
MAPK1	down-regulates	MAPK14
MAPK1	up-regulates	SP1	phosphorylation
MAPK1	up-regulates	RPS6KA5	phosphorylation
MAPK1	up-regulates	SPHK1	phosphorylation
MAPK1	down-regulates	POLR2A	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 128 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
RAF-independent MAPK1/3 activation	7	44.0×	4e-08
MAPK targets/ Nuclear events mediated by MAP kinases	5	26.9×	4e-05
Negative regulation of MAPK pathway	9	23.7×	4e-08
Signaling by RAS mutants	5	20.9×	9e-05
Signaling by high-kinase activity BRAF mutants	6	18.8×	4e-05
MAP kinase activation	6	18.3×	4e-05
Nuclear Events (kinase and transcription factor activation)	5	17.1×	2e-04
MAP2K and MAPK activation	6	17.0×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
MAPK cascade	10	13.0×	6e-06
protein phosphorylation	11	6.3×	9e-04
negative regulation of apoptotic process	13	3.8×	7e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 4 cancer types — CESC, CLLSLL, HCC, HNSC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	6
Uncertain significance	34
Likely benign	13
Benign	3

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
917742	NM_002745.5(MAPK1):c.221T>A (p.Ile74Asn)	Pathogenic
917743	NM_002745.5(MAPK1):c.238C>T (p.His80Tyr)	Pathogenic
917744	NM_002745.5(MAPK1):c.521C>T (p.Ala174Val)	Pathogenic
917746	NM_002745.5(MAPK1):c.953A>G (p.Asp318Gly)	Pathogenic
917749	NM_002745.5(MAPK1):c.968C>G (p.Pro323Arg)	Pathogenic
1804005	NM_002745.5(MAPK1):c.946T>C (p.Tyr316His)	Likely pathogenic
208698	NM_002745.5(MAPK1):c.404G>C (p.Arg135Thr)	Likely pathogenic
3029021	NM_002745.5(MAPK1):c.241G>A (p.Glu81Lys)	Likely pathogenic
3253018	NM_002745.5(MAPK1):c.968C>A (p.Pro323His)	Likely pathogenic
3373126	NM_002745.5(MAPK1):c.357A>C (p.Gln119His)	Likely pathogenic
3587857	NM_002745.5(MAPK1):c.244A>G (p.Asn82Asp)	Likely pathogenic

SpliceAI

2479 predictions. Top by Δscore:

Variant	Effect	Δscore
22:21764010:A:AC	donor_gain	1.0000
22:21764011:C:CC	donor_gain	1.0000
22:21769190:GGTA:G	donor_loss	1.0000
22:21769191:GTA:G	donor_loss	1.0000
22:21769192:TAC:T	donor_loss	1.0000
22:21769193:A:C	donor_loss	1.0000
22:21769194:C:CA	donor_loss	1.0000
22:21769215:AT:A	donor_gain	1.0000
22:21769216:T:TA	donor_gain	1.0000
22:21769265:T:TA	donor_gain	1.0000
22:21769316:ATGGG:A	acceptor_gain	1.0000
22:21769317:TGGG:T	acceptor_gain	1.0000
22:21769318:GGG:G	acceptor_gain	1.0000
22:21769319:GG:G	acceptor_gain	1.0000
22:21769321:C:CC	acceptor_gain	1.0000
22:21769321:CTTTA:C	acceptor_loss	1.0000
22:21769322:T:C	acceptor_gain	1.0000
22:21769322:T:TC	acceptor_gain	1.0000
22:21769323:T:C	acceptor_gain	1.0000
22:21769323:T:TC	acceptor_gain	1.0000
22:21772867:TCTTA:T	donor_loss	1.0000
22:21772868:CTTA:C	donor_loss	1.0000
22:21772869:TTA:T	donor_loss	1.0000
22:21772870:TA:T	donor_loss	1.0000
22:21772871:A:C	donor_loss	1.0000
22:21772872:C:CT	donor_loss	1.0000
22:21772872:CCT:C	donor_gain	1.0000
22:21772978:CAGAG:C	acceptor_gain	1.0000
22:21772979:AGAG:A	acceptor_gain	1.0000
22:21772980:GAG:G	acceptor_gain	1.0000

AlphaMissense

2391 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:21772936:C:A	R301S	1.000
22:21772936:C:G	R301S	1.000
22:21772937:C:A	R301M	1.000
22:21772937:C:G	R301T	1.000
22:21788708:A:G	L237P	1.000
22:21788729:C:T	G230E	1.000
22:21788730:C:A	G230W	1.000
22:21788730:C:G	G230R	1.000
22:21788730:C:T	G230R	1.000
22:21788770:G:C	C216W	1.000
22:21788771:C:T	C216Y	1.000
22:21788774:C:T	G215D	1.000
22:21788775:C:G	G215R	1.000
22:21788782:C:A	W212C	1.000
22:21788782:C:G	W212C	1.000
22:21788784:A:G	W212R	1.000
22:21788784:A:T	W212R	1.000
22:21788789:T:A	D210V	1.000
22:21788790:C:A	D210Y	1.000
22:21788790:C:G	D210H	1.000
22:21799034:G:T	P196Q	1.000
22:21799039:C:A	R194S	1.000
22:21799039:C:G	R194S	1.000
22:21799040:C:A	R194M	1.000
22:21799040:C:G	R194T	1.000
22:21799044:A:G	Y193H	1.000
22:21799047:A:G	W192R	1.000
22:21799047:A:T	W192R	1.000
22:21799050:G:T	R191S	1.000
22:21799052:G:A	T190I	1.000

dbSNP variants (sampled 300 via entrez): RS1000035983 (22:21853987 A>C), RS1000043030 (22:21853391 A>G), RS1000048535 (22:21783210 G>A), RS1000049340 (22:21817378 T>A,C), RS1000050547 (22:21821040 A>G), RS1000052028 (22:21857994 T>C), RS1000057882 (22:21815994 G>C), RS1000109777 (22:21815730 G>C), RS1000152218 (22:21812941 G>A), RS1000154600 (22:21779061 G>A), RS1000157350 (22:21813154 A>G), RS1000163508 (22:21790082 C>T), RS1000223622 (22:21847866 G>A), RS1000225972 (22:21805172 T>C), RS1000239383 (22:21837304 A>T)

Disease associations

OMIM: gene MIM:176948 | disease phenotypes: MIM:619087

GenCC curated gene-disease

Disease	Classification	Inheritance
Noonan syndrome 13	Strong	Autosomal dominant
neurodevelopmental disorder	Strong	Autosomal dominant

Mondo (5): Noonan syndrome 13 (MONDO:0033669), intellectual disability (MONDO:0001071), microcephaly (MONDO:0001149), specific learning disability (MONDO:0016225), neurodevelopmental disorder (MONDO:0700092)

Orphanet (2): Specific learning disability (Orphanet:211047), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

120 total (30 of 120 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000081	Duplicated collecting system
HP:0000154	Wide mouth
HP:0000160	Narrow mouth
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000272	Malar flattening
HP:0000276	Long face
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000307	Pointed chin
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000324	Facial asymmetry
HP:0000341	Narrow forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000363	Abnormal earlobe morphology
HP:0000369	Low-set ears
HP:0000403	Recurrent otitis media
HP:0000407	Sensorineural hearing impairment
HP:0000426	Prominent nasal bridge
HP:0000430	Underdeveloped nasal alae

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001198_31	Multiple sclerosis	5.000000e-09
GCST001725_108	Inflammatory bowel disease	1.000000e-16
GCST005531_71	Multiple sclerosis	6.000000e-16
GCST008103_64	Bipolar disorder	6.000000e-07
GCST009265_12	Superior parietal cortex volume	8.000000e-06
GCST009597_8	Multiple sclerosis	1.000000e-19
GCST010989_163	Body size at age 10	4.000000e-10
GCST011572_1	Serum interleukin-6 concentration in active individuals	1.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009819	comparative body size at age 10, self-reported
EFO:0004810	interleukin-6 measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D065886	Neurodevelopmental Disorders	F03.625
D000067559	Specific Learning Disorder	C10.597.606.150.550.700; C23.888.592.604.150.550.700; F03.625.374.188.700; F03.625.562.700

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL1907606 (PROTEIN FAMILY), CHEMBL3885566 (PROTEIN FAMILY), CHEMBL4040 (SINGLE PROTEIN), CHEMBL6066552 (PROTEIN FAMILY), CHEMBL6195573 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

324 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 660,498 (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
CHEMBL101	PHENYLBUTAZONE	4	59,455
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,194
CHEMBL1017	TELMISARTAN	4	27,457
CHEMBL103	PROGESTERONE	4	162,141
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1051	LATANOPROST	4	14,975
CHEMBL1071	OXAPROZIN	4	51,044
CHEMBL108	CARBAMAZEPINE	4	53,528
CHEMBL1082607	SALMETEROL XINAFOATE	4	15,201
CHEMBL1095292	BRETYLIUM TOSYLATE	4	3,061
CHEMBL110691	CHLORMADINONE ACETATE	4	9,747
CHEMBL1108	DROPERIDOL	4	16,888
CHEMBL1115	PYRIDOSTIGMINE	4	13,658
CHEMBL1117	IDARUBICIN	4	136,065
CHEMBL1165268	IODIPAMIDE	4	2,164
CHEMBL117785	TETRABENAZINE	4	9,645
CHEMBL1198	PRAMOXINE	4	10,295
CHEMBL1200322	ESCITALOPRAM OXALATE	4	2,281
CHEMBL1200326	NICARDIPINE HYDROCHLORIDE	4	3,903
CHEMBL1200334	MORICIZINE HYDROCHLORIDE	4	1,471
CHEMBL1200348	SULCONAZOLE NITRATE	4
CHEMBL1200418	DOBUTAMINE HYDROCHLORIDE	4
CHEMBL1200446	TRIPELENNAMINE HYDROCHLORIDE	4
CHEMBL1200471	PYRITHIONE ZINC	4
CHEMBL1200479	DICYCLOMINE HYDROCHLORIDE	4
CHEMBL1200522	AVOBENZONE	4
CHEMBL1200585	OXYMETHOLONE	4
CHEMBL1200750	PROMETHAZINE HYDROCHLORIDE	4
CHEMBL1200761	CHLOROTRIANISENE	4
CHEMBL1200781	CITALOPRAM HYDROBROMIDE	4

Clinical evidence (CIViC)

Drug × variant × indication: 2 predictive associations from 3 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
MAPK1 E322K	Erlotinib	Head And Neck Squamous Cell Carcinoma	Sensitivity/Response	CIViC C	EID791 +1
MAPK1 Amplification	WZ4002	Lung Non-small Cell Carcinoma	Resistance	CIViC D	EID792

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

PharmGKB variants

5 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6928	MAPK1		0.00	0
rs13515	MAPK1		0.00	0
rs8136867	MAPK1		0.00	0
rs3729910	MAPK1		0.00	0
rs1803545	MAPK1		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — ERK subfamily

Most potent curated ligand interactions (14 total), top 14:

Ligand	Action	Affinity	Parameter
rineterkib	Inhibition	10.58	pIC50
ulixertinib	Inhibition	9.52	pIC50
sonvuterkib	Inhibition	9.27	pIC50
tizaterkib	Inhibition	9.18	pIC50
VTX-11e	Inhibition	8.7	pKi
beroterkib	Inhibition	8.57	pIC50
compound 27 [PMID: 29775310]	Inhibition	8.52	pIC50
ravoxertinib	Inhibition	8.51	pIC50
SCH772984	Inhibition	8.4	pIC50
MK-8353	Inhibition	8.06	pIC50
edaxeterkib	Inhibition	7.3	pIC50
ERK inhibitor II	Inhibition	6.85	pKi
laduviglusib	Inhibition	5.0	pIC50
ERK inhibitor III	Binding	4.89	pKd

Binding affinities (BindingDB)

3712 measured of 4089 human assays (4091 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-[3-amino-6-[(1R,3R,4R)-3,4-dihydroxycyclohexyl]pyrazin-2-yl]-2-fluoro-N-[(1S)-1-(3-fluoro-5-iodophenyl)-2-hydroxyethyl]benzamide	IC50	0.00431 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
4-[3-amino-6-[(1R,3R,4R)-3-fluoro-4-hydroxycyclohexyl]pyrazin-2-yl]-N-[(1S)-2-amino-1-(3-fluoro-5-iodophenyl)ethyl]-2-fluorobenzamide	IC50	0.005 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
4-[3-amino-6-[(1S,3S,4S)-3,4-dihydroxycyclohexyl]pyrazin-2-yl]-2-fluoro-N-[(1S)-1-(3-fluoro-5-iodophenyl)-2-hydroxyethyl]benzamide	IC50	0.0055 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
N-[(1S)-2-amino-1-(3-fluoro-5-iodophenyl)ethyl]-4-[3-amino-6-(oxan-4-yl)pyrazin-2-yl]-2-fluorobenzamide	IC50	0.00612 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
4-[3-amino-6-(4-hydroxycyclohexyl)pyrazin-2-yl]-2-fluoro-N-[(1S)-1-(3-fluoro-5-iodophenyl)-2-(methylamino)ethyl]benzamide	IC50	0.00665 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
N-[(1S)-2-amino-1-(3-bromo-5-fluorophenyl)ethyl]-4-[3-amino-6-(oxan-4-yl)pyrazin-2-yl]-2-fluorobenzamide	IC50	0.00671 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
4-[3-amino-6-(oxan-4-yl)pyrazin-2-yl]-2-fluoro-N-[(1S)-1-(3-fluoro-5-methylsulfanylphenyl)-2-hydroxyethyl]benzamide	IC50	0.00827 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
N-[(1S)-2-amino-1-(3-fluoro-5-iodophenyl)ethyl]-4-[3-amino-6-(4-hydroxycyclohexyl)pyrazin-2-yl]-2-fluorobenzamide	IC50	0.00837 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
4-[2-amino-5-(1,5-dimethylpyrazol-4-yl)-3-pyridinyl]-2-fluoro-N-[(1S)-1-[3-fluoro-5-(fluoromethyl)phenyl]-2-hydroxyethyl]benzamide	IC50	0.00875 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
4-[3-amino-6-[(3R)-6-oxopiperidin-3-yl]pyrazin-2-yl]-2-fluoro-N-[(1S)-1-(3-fluoro-5-iodophenyl)-2-hydroxyethyl]benzamide	IC50	0.009 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
4-[3-amino-6-(oxan-4-yl)pyrazin-2-yl]-N-[(1S)-1-(3-bromophenyl)-2-(methylamino)ethyl]-2-fluorobenzamide	IC50	0.0097 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
4-[3-amino-6-(4-hydroxycyclohexyl)pyrazin-2-yl]-2-fluoro-N-[(1S)-1-(3-fluoro-5-iodophenyl)-2-hydroxyethyl]benzamide	IC50	0.00977 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
4-[3-amino-6-(oxan-4-yl)pyrazin-2-yl]-2-fluoro-N-[(1S)-1-[3-fluoro-5-(fluoromethyl)phenyl]-2-hydroxyethyl]benzamide	IC50	0.01 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
4-[3-amino-6-(oxan-4-yl)pyrazin-2-yl]-2-fluoro-N-[(1S)-2-hydroxy-1-(3-methylsulfanylphenyl)ethyl]benzamide	IC50	0.01 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
N-[(1S)-2-amino-1-(3-bromo-5-fluorophenyl)ethyl]-4-[3-amino-6-[(1R,3S,4R)-3-fluoro-4-hydroxycyclohexyl]pyrazin-2-yl]-2-fluorobenzamide	IC50	0.0103 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
4-[2-amino-5-[1-(difluoromethyl)-3-methylpyrazol-4-yl]-3-pyridinyl]-2-fluoro-N-[(1S)-1-[3-fluoro-5-(fluoromethyl)phenyl]-2-hydroxyethyl]benzamide	IC50	0.0104 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
N-[(1S)-2-amino-1-(3-fluoro-5-iodophenyl)ethyl]-4-[3-amino-6-(4-methoxycyclohexyl)pyrazin-2-yl]-2-fluorobenzamide	IC50	0.0107 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
4-[3-amino-6-(4-hydroxycyclohexyl)pyrazin-2-yl]-N-[(1S)-2-amino-1-(3-iodophenyl)ethyl]-2-fluorobenzamide	IC50	0.011 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
N-[(1S)-2-amino-1-(3-chloro-5-fluorophenyl)ethyl]-4-[3-amino-6-(oxan-4-yl)pyrazin-2-yl]-2-fluorobenzamide	IC50	0.0119 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
4-[2-amino-5-(1,3-dimethylpyrazol-4-yl)-3-pyridinyl]-2-fluoro-N-[(1S)-1-[3-fluoro-5-(fluoromethyl)phenyl]-2-hydroxyethyl]benzamide	IC50	0.0121 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
4-[3-amino-6-(oxan-4-yl)pyrazin-2-yl]-N-[(1S)-1-(3-bromo-5-fluorophenyl)-2-hydroxyethyl]-2-fluorobenzamide	IC50	0.0127 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
N-[(1S)-2-amino-1-(3-bromo-5-fluorophenyl)ethyl]-4-[3-amino-6-[(1R,3R,4R)-3-fluoro-4-hydroxycyclohexyl]pyrazin-2-yl]-2-fluorobenzamide	IC50	0.0139 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
4-[3-amino-6-[(1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl]pyrazin-2-yl]-2-fluoro-N-[(1S)-1-(3-fluoro-5-iodophenyl)-2-hydroxyethyl]benzamide	IC50	0.0139 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
4-[2-amino-5-[1-(difluoromethyl)-5-methylpyrazol-4-yl]-3-pyridinyl]-2-fluoro-N-[(1S)-1-[3-fluoro-5-(fluoromethyl)phenyl]-2-hydroxyethyl]benzamide	IC50	0.014 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
4-[3-amino-6-(oxan-4-yl)pyrazin-2-yl]-N-[(1S)-1-(3-chloro-5-fluorophenyl)-2-(methylamino)ethyl]-2-fluorobenzamide	IC50	0.0143 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
4-[3-amino-6-[(1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl]pyrazin-2-yl]-2-fluoro-N-[(1S)-1-(3-fluoro-5-iodophenyl)-2-(methylamino)ethyl]benzamide	IC50	0.0143 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
4-[3-amino-6-(1,3-dimethylpyrazol-4-yl)pyrazin-2-yl]-2-fluoro-N-[(1S)-1-(3-fluoro-5-methylsulfanylphenyl)-2-hydroxyethyl]benzamide	IC50	0.0153 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
4-[2-amino-5-(3-methyltriazol-4-yl)-3-pyridinyl]-2-fluoro-N-[(1S)-1-(3-fluoro-5-iodophenyl)-2-hydroxyethyl]benzamide	IC50	0.0158 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
4-[2-amino-5-[1-(difluoromethyl)-3-methylpyrazol-4-yl]-3-pyridinyl]-2-fluoro-N-[(1S)-1-[3-(fluoromethyl)phenyl]-2-hydroxyethyl]benzamide	IC50	0.0168 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
4-[3-amino-6-(4-hydroxycyclohexyl)pyrazin-2-yl]-N-[(1S)-1-(3-bromo-5-fluorophenyl)-2-hydroxyethyl]-2-fluorobenzamide	IC50	0.0173 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
4-[3-amino-6-(4-hydroxycyclohexyl)pyrazin-2-yl]-2-fluoro-N-[(1S)-2-hydroxy-1-(3-iodophenyl)ethyl]benzamide	IC50	0.0175 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
4-[3-amino-6-[(1R,3R,4R)-3-fluoro-4-hydroxycyclohexyl]pyrazin-2-yl]-2-fluoro-N-[(1S)-1-(3-fluoro-5-iodophenyl)-2-hydroxyethyl]benzamide	IC50	0.0176 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
4-[3-amino-6-(4-hydroxycyclohexyl)pyrazin-2-yl]-N-[(1S)-1-(3-bromo-5-fluorophenyl)-2-(methylamino)ethyl]-2-fluorobenzamide	IC50	0.0183 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
4-[3-amino-6-[(1R,3R,4R)-3,4-dihydroxycyclohexyl]pyrazin-2-yl]-N-[(1S)-1-(3-bromo-5-fluorophenyl)-2-hydroxyethyl]-2-fluorobenzamide	IC50	0.0187 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
4-[2-amino-5-(1,5-dimethylpyrazol-4-yl)-3-pyridinyl]-N-[(1S)-1-(3-chlorophenyl)-2-hydroxyethyl]-2-fluorobenzamide	IC50	0.0187 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
N-[(1S)-2-amino-1-(3-bromo-5-fluorophenyl)ethyl]-4-[3-amino-6-[(1S,3R,4S)-3-fluoro-4-hydroxycyclohexyl]pyrazin-2-yl]-2-fluorobenzamide	IC50	0.0194 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
4-[3-amino-6-(oxan-4-yl)pyrazin-2-yl]-2-fluoro-N-[(1S)-1-[3-(fluoromethyl)phenyl]-2-hydroxyethyl]benzamide	IC50	0.0197 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
4-[3-amino-6-(4-hydroxycyclohexyl)pyrazin-2-yl]-2-fluoro-N-[(1S)-1-(3-fluoro-5-methylsulfanylphenyl)-2-hydroxyethyl]benzamide	IC50	0.0198 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
4-[2-amino-5-(1-methylpyrazol-4-yl)-3-pyridinyl]-2-fluoro-N-[(1S)-1-[3-fluoro-5-(fluoromethyl)phenyl]-2-hydroxyethyl]benzamide	IC50	0.0199 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
N-[(1S)-2-amino-1-(3-bromophenyl)ethyl]-4-[3-amino-6-(oxan-4-yl)pyrazin-2-yl]-2-fluorobenzamide	IC50	0.02 nM	US-9242996: Aminoheteroaryl benzamides as kinase inhibitors
N-(1-methyl-1H-pyrazol-5- yl)-4-(3-phenyl-4,5-dihydro- 3H-1,2,2a1,5- tetraazaacenaphthylen-7- yl)pyrimidin-2-amine	IC50	0.02 nM	US-10278975: Serine/threonine kinase inhibitors
4-(3-benzyl-3,4-dihydro-5- oxa-1,2,2a1- triazaacenaphthylen-7-yl)-N- (1-methyl-1H-pyrazol-5- yl)pyrimidin-2-amine	IC50	0.02 nM	US-9867833: Serine/threonine kinase inhibitors
3-benzyl-5-methyl-7-(2-((1- methyl-1H-pyrazol-5- yl)amino)pyrimidin-4-yl)- 3H-1,2,2a1,3,5- pentaazaacenaphthylen- 4(5H)-one	IC50	0.02 nM	US-9867833: Serine/threonine kinase inhibitors
4-(3-benzyl-3,4-dihydro-5- oxa-1,2,2a1- triazaacenaphthylen-7-yl)-N- (1-methyl-1H-pyrazol-5- yl)pyridin-2-amine	IC50	0.02 nM	US-9867833: Serine/threonine kinase inhibitors
4-(3-(4-methoxybenzyl)-3,4- dihydro-5-oxa-1,2,2a1- triazaacenaphthylen-7-yl)-N- (1-methyl-1H-pyrazol-5- yl)pyrimidin-2-amine	IC50	0.02 nM	US-9867833: Serine/threonine kinase inhibitors
4-[12-(4-fluorophenoxy)-9-oxa-2,3,13-triazatricyclo[6.4.1.04,13]trideca-1,3,5,7-tetraen-6-yl]-N-(2-methylpyrazol-3-yl)pyrimidin-2-amine	IC50	0.02 nM	US-9867833: Serine/threonine kinase inhibitors
4-(3-benzyl-3,4-dihydro-5- oxa-1,2,2a1- triazaacenaphthylen-7-yl)-N- (1-methyl-1H-pyrazol-5- yl)pyrimidin-2-amine	IC50	0.02 nM	US-10278975: Serine/threonine kinase inhibitors
4-(3-benzyl-3,4-dihydro-5- oxa-1,2,2a1- triazaacenaphthylen-7-yl)-N- (1-methyl-1H-pyrazol-5- yl)pyridin-2-amine	IC50	0.02 nM	US-10278975: Serine/threonine kinase inhibitors
4-(3-(4-methoxybenzyl)-3,4- dihydro-5-oxa-1,2,2a1- triazaacenaphthylen-7-yl)-N- (1-methyl-1H-pyrazol-5- yl)pyrimidin-2-amine	IC50	0.02 nM	US-10278975: Serine/threonine kinase inhibitors
4-[(12S)-12-(4-fluorophenoxy)-9-oxa-2,3,13-triazatricyclo[6.4.1.04,13]trideca-1,3,5,7-tetraen-6-yl]-N-(2-methylpyrazol-3-yl)pyrimidin-2-amine	IC50	0.02 nM	US-10278975: Serine/threonine kinase inhibitors

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CHEMBL3608588
11.00	IC50	0.01	nM	CHEMBL4114147
11.00	IC50	0.01	nM	CHEMBL4108345
11.00	IC50	0.01	nM	CHEMBL318804
10.99	IC50	0.0103	nM	CHEMBL4109252
10.98	IC50	0.0104	nM	CHEMBL3957670
10.97	IC50	0.0107	nM	CHEMBL4107945
10.96	IC50	0.011	nM	CHEMBL4109456
10.92	IC50	0.0119	nM	CHEMBL3923033
10.92	IC50	0.0121	nM	CHEMBL4110508
10.90	IC50	0.0127	nM	CHEMBL4108076
10.86	IC50	0.0139	nM	CHEMBL3956128
10.86	IC50	0.0139	nM	CHEMBL4107980
10.85	IC50	0.014	nM	CHEMBL4109206
10.84	IC50	0.0143	nM	CHEMBL4115307
10.84	IC50	0.0143	nM	CHEMBL3923915
10.82	IC50	0.0153	nM	CHEMBL4109955
10.80	IC50	0.0158	nM	CHEMBL4106909
10.77	IC50	0.0168	nM	CHEMBL4113157
10.76	IC50	0.0173	nM	CHEMBL4107833
10.76	IC50	0.0175	nM	CHEMBL4114947
10.75	IC50	0.0176	nM	CHEMBL3913471
10.74	IC50	0.0183	nM	CHEMBL4108962
10.73	IC50	0.0187	nM	CHEMBL3905175
10.73	IC50	0.0187	nM	CHEMBL4114300
10.72	IC50	0.019	nM	CHEMBL3608589
10.71	IC50	0.0197	nM	CHEMBL4106814
10.71	IC50	0.0194	nM	CHEMBL3930522
10.70	IC50	0.0199	nM	CHEMBL4113452
10.70	IC50	0.0198	nM	CHEMBL4114593
10.70	IC50	0.0201	nM	CHEMBL4108926
10.70	IC50	0.02	nM	CHEMBL4108313
10.70	IC50	0.02	nM	CHEMBL5880878
10.70	IC50	0.02	nM	CHEMBL5904041
10.70	IC50	0.02	nM	CHEMBL6045548
10.70	IC50	0.02	nM	CHEMBL5846324
10.70	IC50	0.02	nM	CHEMBL5797207
10.70	IC50	0.02	nM	CHEMBL5908683
10.70	IC50	0.02	nM	CHEMBL5894810
10.70	IC50	0.02	nM	CHEMBL5852694
10.70	IC50	0.02	nM	CHEMBL5997841
10.70	IC50	0.02	nM	CHEMBL5928779
10.70	IC50	0.02	nM	CHEMBL5806164
10.70	IC50	0.02	nM	CHEMBL5863069
10.70	IC50	0.02	nM	CHEMBL5999003
10.69	IC50	0.0205	nM	CHEMBL4115371
10.69	IC50	0.0205	nM	CHEMBL4108747
10.68	IC50	0.021	nM	CHEMBL3928081
10.68	IC50	0.0209	nM	CHEMBL4107676
10.68	IC50	0.0208	nM	CHEMBL4113751

PubChem BioAssay actives

1256 with measured affinity, of 4497 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
4-[3-chloro-4-(1-methylimidazol-2-yl)sulfanylanilino]-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinoline-3-carbonitrile	102178: Inhibit ion of MAPK phosphorylation in LoVo cells	ic50	<0.0001	uM
N-[(1S)-1-(3-chlorophenyl)-2-hydroxyethyl]-4-[5-chloro-2-(propan-2-ylamino)-4-pyridinyl]-1H-pyrrole-2-carboxamide	1243393: Inhibition of ERK2 (unknown origin)	ic50	<0.0001	uM
2-[(1S)-2-hydroxy-1-phenylethyl]-8-[2-(oxan-4-ylamino)pyrimidin-4-yl]-4,5-dihydro-3H-pyrrolo[1,2-a][1,4]diazepin-1-one	1243393: Inhibition of ERK2 (unknown origin)	ic50	<0.0001	uM
2-[(1S)-2-hydroxy-1-phenylethyl]-8-[2-(2-oxaspiro[3.3]heptan-6-ylamino)pyrimidin-4-yl]-4,5-dihydro-3H-pyrrolo[1,2-a][1,4]diazepin-1-one	1243393: Inhibition of ERK2 (unknown origin)	ic50	<0.0001	uM
2-[(1S)-1-(3-chlorophenyl)-2-hydroxyethyl]-8-[2-[(3-fluorooxan-4-yl)amino]pyrimidin-4-yl]-4,5-dihydro-3H-pyrrolo[1,2-a][1,4]diazepin-1-one	1243393: Inhibition of ERK2 (unknown origin)	ic50	<0.0001	uM
2-[(1S)-1-(3-chlorophenyl)-2-hydroxyethyl]-8-[2-[[(1S,5R)-3-oxabicyclo[3.1.0]hexan-6-yl]amino]pyrimidin-4-yl]-4,5-dihydro-3H-pyrrolo[1,2-a][1,4]diazepin-1-one	1243393: Inhibition of ERK2 (unknown origin)	ic50	<0.0001	uM
2-[(1S)-1-(3-chloro-5-fluorophenyl)-2-hydroxyethyl]-8-[2-(oxan-4-ylamino)pyrimidin-4-yl]-4,5-dihydro-3H-pyrrolo[1,2-a][1,4]diazepin-1-one	1243393: Inhibition of ERK2 (unknown origin)	ic50	<0.0001	uM
2-[(1S)-1-(3-chlorophenyl)-2-hydroxyethyl]-8-[2-(oxan-4-ylamino)pyrimidin-4-yl]-4,5-dihydro-3H-pyrrolo[1,2-a][1,4]diazepin-1-one	1243393: Inhibition of ERK2 (unknown origin)	ic50	<0.0001	uM
6,6-dimethyl-2-[2-[(2-methylpyrazol-3-yl)amino]pyrimidin-4-yl]-5-(2-morpholin-4-ylethyl)thieno[2,3-c]pyrrol-4-one	1896218: Binding affinity to ERK2 (unknown origin)	ki	0.0001	uM
(4R)-2-[(1S)-1-(3-chlorophenyl)-2-hydroxyethyl]-4-fluoro-8-[2-(oxan-4-ylamino)pyrimidin-4-yl]-4,5-dihydro-3H-pyrrolo[1,2-a][1,4]diazepin-1-one	1243393: Inhibition of ERK2 (unknown origin)	ic50	0.0001	uM
(6R)-7-[(3,4-difluorophenyl)methyl]-6-(methoxymethyl)-2-[5-methyl-2-[(2-methylpyrazol-3-yl)amino]pyrimidin-4-yl]-5,6-dihydroimidazo[1,2-a]pyrazin-8-one	1527704: Binding affinity to non-phosphorylated biotinylated ERK2 (unknown origin) by SPR analysis	kd	0.0001	uM
2-[(3-chlorophenyl)methyl]-7-[5-methyl-2-[(2-methylpyrazol-3-yl)amino]pyrimidin-4-yl]-3,4-dihydropyrrolo[1,2-a]pyrazin-1-one	1527682: Inhibition of MEK U911-activated ERK2 (unknown origin) using ERKtide as substrate preincubated for 20 mins followed by substrate addition in presence of 1 mM ATP after 10 mins by rapidfire mass spectrometry analysis	ic50	0.0001	uM
4-[5-chloro-2-[(2-methyl-4-pyridinyl)amino]pyrimidin-4-yl]-N-[(1S)-2-hydroxy-1-phenylethyl]thiophene-2-carboxamide	2083146: Inhibition of ERK2 (unknown origin) assessed as luminescence in presence of ATP incubated for 90 mins by ADP-Glo kinase assay	ic50	0.0001	uM
4-[5-chloro-2-[(2-methylpyrazol-3-yl)amino]pyrimidin-4-yl]-N-[(3-methoxyphenyl)methyl]thiophene-2-carboxamide	2083146: Inhibition of ERK2 (unknown origin) assessed as luminescence in presence of ATP incubated for 90 mins by ADP-Glo kinase assay	ic50	0.0001	uM
N-[(3-chloro-4-fluorophenyl)methyl]-4-[5-chloro-2-[(3-methyl-4-pyridinyl)amino]pyrimidin-4-yl]thiophene-2-carboxamide	2083146: Inhibition of ERK2 (unknown origin) assessed as luminescence in presence of ATP incubated for 90 mins by ADP-Glo kinase assay	ic50	0.0001	uM
4-[5-chloro-2-[(2-methyl-4-pyridinyl)amino]pyrimidin-4-yl]-N-[(1S)-1-(3-chlorophenyl)-2-hydroxyethyl]thiophene-2-carboxamide	2083146: Inhibition of ERK2 (unknown origin) assessed as luminescence in presence of ATP incubated for 90 mins by ADP-Glo kinase assay	ic50	0.0001	uM
(3R)-1-[2-oxo-2-[4-(4-pyrimidin-2-ylphenyl)piperazin-1-yl]ethyl]-N-(3-pyridin-4-yl-1H-indazol-5-yl)pyrrolidine-3-carboxamide	1527704: Binding affinity to non-phosphorylated biotinylated ERK2 (unknown origin) by SPR analysis	kd	0.0001	uM
1-[2-hydroxy-1-(3-methoxyphenyl)ethyl]-4-[2-(oxan-4-ylamino)pyrimidin-4-yl]pyridin-2-one	1197513: Inhibition of 6-His tagged human ERK2 expressed in Escherichia coli measured over 30 mins by competition assay	ki	0.0001	uM
1-[1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl]-4-[5-fluoro-2-(oxan-4-ylamino)pyrimidin-4-yl]pyridin-2-one	1197513: Inhibition of 6-His tagged human ERK2 expressed in Escherichia coli measured over 30 mins by competition assay	ki	0.0001	uM
1-[1-(3-chloro-5-fluorophenyl)-2-hydroxyethyl]-4-[2-(oxan-4-ylamino)pyrimidin-4-yl]pyridin-2-one	1197513: Inhibition of 6-His tagged human ERK2 expressed in Escherichia coli measured over 30 mins by competition assay	ki	0.0001	uM
N-[(1S)-1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl]-2-(oxan-4-ylamino)-6,8-dihydro-5H-pyrido[3,4-d]pyrimidine-7-carboxamide	2015525: Binding affinity to ERK2 (unknown origin) using Ulight-MBP as substrate assessed as inhibition constant preincubated for 30 mins followed by substrate addition measured after 90 mins in presence of ATP by TR-FRET assay	ki	0.0001	uM
1-[1-(4-chlorophenyl)-2-hydroxyethyl]-4-[2-(oxan-4-ylamino)pyrimidin-4-yl]pyridin-2-one	1197513: Inhibition of 6-His tagged human ERK2 expressed in Escherichia coli measured over 30 mins by competition assay	ki	0.0001	uM
1-[(3-bromophenyl)methyl]-4-(3-pyridin-4-yl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl)pyridin-2-one	1239893: Inhibition of ERK2 (unknown origin)	ic50	0.0002	uM
(3R)-3-methyl-7-[5-methyl-2-[(2-methylpyrazol-3-yl)amino]pyrimidin-4-yl]-2-[(6-methyl-2-pyridinyl)methyl]-3,4-dihydropyrrolo[1,2-a]pyrazin-1-one	1527705: Binding affinity to MEK-activated phosphorylated biotinylated ERK2 (unknown origin) by SPR analysis	kd	0.0002	uM
(3R)-2-(2-methoxyethyl)-3-methyl-7-[5-methyl-2-[(2-methylpyrazol-3-yl)amino]pyrimidin-4-yl]-3,4-dihydropyrrolo[1,2-a]pyrazin-1-one	1482242: Inhibition of ERK2 (unknown origin) in the presence of 1 mM ATP	ic50	0.0002	uM
N-[(1S)-1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl]-2-(oxan-4-ylamino)quinazoline-7-carboxamide	2015525: Binding affinity to ERK2 (unknown origin) using Ulight-MBP as substrate assessed as inhibition constant preincubated for 30 mins followed by substrate addition measured after 90 mins in presence of ATP by TR-FRET assay	ki	0.0002	uM
N-[(1S)-1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl]-2-(oxan-4-ylamino)pyrido[2,3-d]pyrimidine-7-carboxamide	2015525: Binding affinity to ERK2 (unknown origin) using Ulight-MBP as substrate assessed as inhibition constant preincubated for 30 mins followed by substrate addition measured after 90 mins in presence of ATP by TR-FRET assay	ki	0.0002	uM
N-[(3-chloro-4-fluorophenyl)methyl]-4-[5-chloro-2-[(2-methylpyrazol-3-yl)amino]pyrimidin-4-yl]thiophene-2-carboxamide	2083146: Inhibition of ERK2 (unknown origin) assessed as luminescence in presence of ATP incubated for 90 mins by ADP-Glo kinase assay	ic50	0.0002	uM
1-[3-(2-methyl-4-pyridinyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea	1626505: Inhibition of human ERK2 preincubated for 15 mins followed by addition of IMAP peptide substrate and ATP measured after 60 mins by IMAP-FP assay	ic50	0.0002	uM
1-[(1S)-1-(3-fluorophenyl)-2-hydroxyethyl]-4-[2-(oxan-4-ylamino)pyrimidin-4-yl]pyridin-2-one	1197513: Inhibition of 6-His tagged human ERK2 expressed in Escherichia coli measured over 30 mins by competition assay	ki	0.0002	uM
1-[1-(3,5-dichlorophenyl)-2-hydroxyethyl]-4-[2-(oxan-4-ylamino)pyrimidin-4-yl]pyridin-2-one	1197513: Inhibition of 6-His tagged human ERK2 expressed in Escherichia coli measured over 30 mins by competition assay	ki	0.0002	uM
1-[1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl]-4-[5-chloro-2-(oxan-4-ylamino)pyrimidin-4-yl]pyridin-2-one	1197513: Inhibition of 6-His tagged human ERK2 expressed in Escherichia coli measured over 30 mins by competition assay	ki	0.0002	uM
8-[2-[[(1R,3S,4S)-3-fluoro-4-hydroxycyclopentyl]amino]pyrimidin-4-yl]-2-[(1S)-2-hydroxy-1-phenylethyl]-4,5-dihydro-3H-pyrrolo[1,2-a][1,4]diazepin-1-one	1243393: Inhibition of ERK2 (unknown origin)	ic50	0.0002	uM
2-[(1S)-1-(3-chlorophenyl)-2-hydroxyethyl]-7-[2-(oxan-4-ylamino)pyrimidin-4-yl]-3,4-dihydropyrrolo[1,2-a]pyrazin-1-one	1243393: Inhibition of ERK2 (unknown origin)	ic50	0.0002	uM
2-[(1S)-1-(3-chlorophenyl)-2-hydroxyethyl]-8-[2-[[(1S,3R)-3-hydroxycyclopentyl]amino]pyrimidin-4-yl]-4,5-dihydro-3H-pyrrolo[1,2-a][1,4]diazepin-1-one	1243393: Inhibition of ERK2 (unknown origin)	ic50	0.0002	uM
Tivozanib	2159224: Inhibition of ERK2 phosphorylation in VEGF-stimulated serum-starved human HUVEC cells by immunoblotting analysis	ic50	0.0002	uM
1-[(3-chlorophenyl)methyl]-4-(3-pyridin-4-yl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl)pyridin-2-one	1239893: Inhibition of ERK2 (unknown origin)	ic50	0.0003	uM
2-[(1S)-1-(3-chlorophenyl)-2-hydroxyethyl]-8-[2-[[(1R,4S)-3,3-difluoro-4-hydroxycyclopentyl]amino]pyrimidin-4-yl]-4,5-dihydro-3H-pyrrolo[1,2-a][1,4]diazepin-1-one	1243393: Inhibition of ERK2 (unknown origin)	ic50	0.0003	uM
(3S)-2-(2-methoxyethyl)-3-methyl-7-[5-methyl-2-[(2-methylpyrazol-3-yl)amino]pyrimidin-4-yl]-3,4-dihydropyrrolo[1,2-a]pyrazin-1-one	1482241: Inhibition of ERK2 (unknown origin) in the presence of 60 uM ATP	ic50	0.0003	uM
7-[5-methyl-2-[(2-methylpyrazol-3-yl)amino]pyrimidin-4-yl]-2-[(6-methyl-2-pyridinyl)methyl]-3,4-dihydropyrrolo[1,2-a]pyrazin-1-one	1482241: Inhibition of ERK2 (unknown origin) in the presence of 60 uM ATP	ic50	0.0003	uM
(3R)-3-(methoxymethyl)-7-[5-methyl-2-[(2-methylpyrazol-3-yl)amino]pyrimidin-4-yl]-2-[(6-methyl-2-pyridinyl)methyl]-3,4-dihydropyrrolo[1,2-a]pyrazin-1-one	1527681: Inhibition of MEK U911-activated ERK2 (unknown origin) using ERKtide as substrate preincubated for 20 mins followed by substrate addition in presence of ATP at Km concentration after 20 mins by rapidfire mass spectrometry analysis	ic50	0.0003	uM
(3S)-3-methyl-7-[5-methyl-2-[(2-methylpyrazol-3-yl)amino]pyrimidin-4-yl]-2-[(6-methyl-2-pyridinyl)methyl]-3,4-dihydropyrrolo[1,2-a]pyrazin-1-one	1482241: Inhibition of ERK2 (unknown origin) in the presence of 60 uM ATP	ic50	0.0003	uM
5-benzyl-2-[2-(oxan-4-ylamino)pyrimidin-4-yl]-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4-one	1482241: Inhibition of ERK2 (unknown origin) in the presence of 60 uM ATP	ic50	0.0003	uM
(6R)-5-(2-methoxyethyl)-6-methyl-2-[5-methyl-2-[(2-methylpyrazol-3-yl)amino]pyrimidin-4-yl]-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4-one	1482241: Inhibition of ERK2 (unknown origin) in the presence of 60 uM ATP	ic50	0.0003	uM
(6S)-5-(2-methoxyethyl)-6-methyl-2-[5-methyl-2-[(2-methylpyrazol-3-yl)amino]pyrimidin-4-yl]-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4-one	1482241: Inhibition of ERK2 (unknown origin) in the presence of 60 uM ATP	ic50	0.0003	uM
7-[(3-chlorophenyl)methyl]-2-[5-methyl-2-[(2-methylpyrazol-3-yl)amino]pyrimidin-4-yl]-5,6-dihydroimidazo[1,2-a]pyrazin-8-one	1527681: Inhibition of MEK U911-activated ERK2 (unknown origin) using ERKtide as substrate preincubated for 20 mins followed by substrate addition in presence of ATP at Km concentration after 20 mins by rapidfire mass spectrometry analysis	ic50	0.0003	uM
(6S)-7-[(3,4-difluorophenyl)methyl]-6-methyl-2-[5-methyl-2-[(2-methylpyrazol-3-yl)amino]pyrimidin-4-yl]-5,6-dihydroimidazo[1,2-a]pyrazin-8-one	1527681: Inhibition of MEK U911-activated ERK2 (unknown origin) using ERKtide as substrate preincubated for 20 mins followed by substrate addition in presence of ATP at Km concentration after 20 mins by rapidfire mass spectrometry analysis	ic50	0.0003	uM
(6S)-5-(2-methoxyethyl)-6-methyl-2-[2-[(2-methylpyrazol-3-yl)amino]pyrimidin-4-yl]-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4-one	1482241: Inhibition of ERK2 (unknown origin) in the presence of 60 uM ATP	ic50	0.0003	uM
2-(2-methoxyethyl)-7-[5-methyl-2-[(2-methylpyrazol-3-yl)amino]pyrimidin-4-yl]-3,4-dihydropyrrolo[1,2-a]pyrazin-1-one	1482241: Inhibition of ERK2 (unknown origin) in the presence of 60 uM ATP	ic50	0.0003	uM
3-methyl-7-[2-[(2-methylpyrazol-3-yl)amino]pyrimidin-4-yl]-2-[(6-methyl-2-pyridinyl)methyl]-3,4-dihydropyrrolo[1,2-a]pyrazin-1-one	1482242: Inhibition of ERK2 (unknown origin) in the presence of 1 mM ATP	ic50	0.0003	uM

CTD chemical–gene interactions

1286 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	increases phosphorylation, increases reaction, increases abundance, affects cotreatment, decreases reaction (+10 more)	180
U 0126	decreases expression, decreases activity, increases phosphorylation, increases abundance, affects localization (+10 more)	156
Tetradecanoylphorbol Acetate	affects localization, increases activity, affects reaction, decreases activity, increases localization (+5 more)	69
Acetylcysteine	increases phosphorylation, decreases expression, decreases activity, decreases reaction, increases activity (+4 more)	65
Resveratrol	affects reaction, affects cotreatment, decreases phosphorylation, decreases reaction, increases activity (+10 more)	62
sodium arsenite	decreases phosphorylation, increases phosphorylation, increases expression, increases abundance, affects cotreatment (+8 more)	58
Arsenic Trioxide	affects cotreatment, decreases phosphorylation, increases reaction, affects expression, decreases activity (+7 more)	52
Cadmium Chloride	increases reaction, increases abundance, affects cotreatment, decreases response to substance, affects activity (+7 more)	45
bisphenol A	decreases activity, decreases expression, decreases phosphorylation, increases reaction, increases expression (+8 more)	44
Estradiol	decreases reaction, increases activity, decreases expression, decreases phosphorylation, increases expression (+7 more)	42
RTKI cpd	decreases reaction, affects cotreatment, increases reaction, increases activity, increases phosphorylation (+3 more)	39
Quercetin	increases activity, affects binding, decreases reaction, increases expression, increases phosphorylation (+4 more)	39
Cadmium	decreases reaction, affects cotreatment, affects phosphorylation, affects uptake, increases abundance (+6 more)	35
Hydrogen Peroxide	decreases phosphorylation, increases abundance, increases localization, decreases reaction, increases activity (+5 more)	30
Particulate Matter	decreases expression, affects localization, increases phosphorylation, increases expression, affects reaction (+6 more)	30
Lipopolysaccharides	increases phosphorylation, increases reaction, decreases reaction, affects reaction, increases abundance (+3 more)	27
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	increases activity, increases phosphorylation, increases reaction, decreases activity, affects cotreatment (+4 more)	25
Sorafenib	decreases response to substance, increases phosphorylation, decreases phosphorylation, affects phosphorylation, affects cotreatment (+4 more)	25
Gefitinib	affects cotreatment, increases expression, affects reaction, decreases reaction, increases reaction (+6 more)	22
Fulvestrant	decreases phosphorylation, affects cotreatment, increases activity, decreases response to substance, decreases reaction (+2 more)	22
Cisplatin	decreases reaction, increases activity, increases phosphorylation, affects activity, decreases response to substance (+5 more)	18
Doxorubicin	affects activity, affects phosphorylation, decreases expression, decreases phosphorylation, decreases response to substance (+8 more)	17
Curcumin	decreases reaction, increases phosphorylation, increases activity, affects cotreatment, increases response to substance (+6 more)	16
Plant Extracts	increases reaction, decreases reaction, increases phosphorylation, affects phosphorylation, affects reaction (+3 more)	16
Wortmannin	affects cotreatment, decreases reaction, increases phosphorylation, increases reaction, increases activity (+2 more)	15
Benzo(a)pyrene	increases expression, decreases reaction, increases phosphorylation, increases reaction, increases abundance (+5 more)	15
Nicotine	increases activity, decreases reaction, increases phosphorylation, increases expression, affects reaction (+5 more)	15
4-((3-bromophenyl)amino)-6,7-dimethoxyquinazoline	decreases activity, decreases phosphorylation, affects cotreatment, decreases reaction, increases phosphorylation (+2 more)	14
4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-3H-cyclopenta(c)quinoline	decreases phosphorylation, decreases reaction, increases activity, increases phosphorylation, increases reaction (+2 more)	14
Tretinoin	decreases reaction, increases phosphorylation, increases activity, affects cotreatment, affects phosphorylation (+4 more)	14

ChEMBL screening assays

1369 unique, capped per target: 1348 binding, 16 functional, 5 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1008211	Binding	Inhibition of ERK1/2 phosphorylation in human MALME3M cells	Potent and selective pyrazole-based inhibitors of B-Raf kinase. — Bioorg Med Chem Lett
CHEMBL4423934	ADMET	Effect on ERK1/2 phosphorylation at T202/Y204 residues in mouse RAW264.7 cells at 5 uM measured after 30 mins by Western blot analysis	Physalactone and 4β-Hydroxywithanolide E Isolated from Physalis peruviana Inhibit LPS-Induced Expression of COX-2 and iNOS Accompanied by Abatement of Akt and STAT1. — J Nat Prod
CHEMBL709032	Functional	Inhibit ion of MAPK phosphorylation in LoVo cells	Synthesis and evaluation of 4-anilino-6,7-dialkoxy-3-quinolinecarbonitriles as inhibitors of kinases of the Ras-MAPK signaling cascade. — Bioorg Med Chem Lett

Cellosaurus cell lines

39 cell lines: 38 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0126	5637	Cancer cell line	Male
CVCL_0179	BT-474	Cancer cell line	Female
CVCL_4V65	BT474-5FU[r]	Cancer cell line	Female
CVCL_4Y08	BT-474/CMV-Luc	Cancer cell line	Female
CVCL_6344	5637 subclone 1A6	Cancer cell line	Male
CVCL_A2GH	LR-BT474	Cancer cell line	Female
CVCL_A4AK	BT-474 Tam2	Cancer cell line	Female
CVCL_A4CL	BT-474 Ecadherin EmGFP	Cancer cell line	Female
CVCL_AQ07	BT-474 Clone 5	Cancer cell line	Female
CVCL_AR86	BT-474 Tam1	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays