RPS6KA5

Summary

RPS6KA5 (ribosomal protein S6 kinase A5, HGNC:10434) is a protein-coding gene on chromosome 14q32.11, encoding Ribosomal protein S6 kinase alpha-5 (O75582). Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factors RELA, STAT3 and ETV1/ER81, and that contributes to gene activation by histone phosph….

Enables ATP binding activity and protein kinase activity. Involved in several processes, including interleukin-1-mediated signaling pathway; protein modification process; and regulation of DNA-templated transcription. Located in cytoplasm and nucleoplasm.

Source: NCBI Gene 9252 — RefSeq curated summary.

At a glance

• GWAS associations: 23
• Clinical variants (ClinVar): 94 total
• Druggable target: yes — 25 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_004755

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10434
Approved symbol	RPS6KA5
Name	ribosomal protein S6 kinase A5
Location	14q32.11
Locus type	gene with protein product
Status	Approved
Aliases	MSK1, RLPK
Ensembl gene	ENSG00000100784
Ensembl biotype	protein_coding
OMIM	603607
Entrez	9252

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 12 protein_coding, 4 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000418736, ENST00000536315, ENST00000554206, ENST00000556178, ENST00000556304, ENST00000556594, ENST00000614987, ENST00000648062, ENST00000886635, ENST00000886636, ENST00000886637, ENST00000886638, ENST00000886639, ENST00000946930, ENST00000946931, ENST00000946932, ENST00000946933

RefSeq mRNA: 14 — MANE Select: NM_004755 NM_001322227, NM_001322228, NM_001322229, NM_001322230, NM_001322231, NM_001322232, NM_001322233, NM_001322234, NM_001322235, NM_001322236, NM_001322237, NM_001322238, NM_004755, NM_182398

CCDS: CCDS45149, CCDS81839, CCDS9893

Canonical transcript exons

ENST00000614987 — 17 exons

Exon	Start	End
ENSE00000659690	90947435	90947550
ENSE00002532615	91060332	91060641
ENSE00003470942	90875201	90875360
ENSE00003499312	90906149	90906299
ENSE00003500697	90923113	90923196
ENSE00003501897	90943078	90943185
ENSE00003525052	90890487	90890678
ENSE00003546891	91001088	91001159
ENSE00003560051	90899329	90899422
ENSE00003564120	90978306	90978524
ENSE00003620587	90873632	90873795
ENSE00003628614	90900108	90900241
ENSE00003677962	90920206	90920309
ENSE00003683166	90894413	90894583
ENSE00003688732	90902808	90902969
ENSE00003688941	90900611	90900736
ENSE00003714652	90847861	90872322

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 95.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.9175 / max 568.3563, expressed in 1275 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
144483	8.5131	1225
144484	0.8440	362
144482	0.5340	239
144481	0.0264	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	95.08	gold quality
cauda epididymis	UBERON:0004360	94.81	gold quality
nipple	UBERON:0002030	93.64	gold quality
corpus callosum	UBERON:0002336	93.57	gold quality
inferior vagus X ganglion	UBERON:0005363	93.05	gold quality
buccal mucosa cell	CL:0002336	92.89	gold quality
Brodmann (1909) area 23	UBERON:0013554	92.61	gold quality
pons	UBERON:0000988	92.39	gold quality
bronchial epithelial cell	CL:0002328	91.16	gold quality
oocyte	CL:0000023	91.00	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	90.79	gold quality
mammary duct	UBERON:0001765	90.65	gold quality
epithelium of mammary gland	UBERON:0003244	90.62	gold quality
skin of hip	UBERON:0001554	90.54	gold quality
epithelium of bronchus	UBERON:0002031	90.54	gold quality
bronchus	UBERON:0002185	90.39	gold quality
body of tongue	UBERON:0011876	90.38	gold quality
orbitofrontal cortex	UBERON:0004167	90.36	gold quality
superior surface of tongue	UBERON:0007371	90.24	gold quality
Brodmann (1909) area 46	UBERON:0006483	90.17	gold quality
superior vestibular nucleus	UBERON:0007227	89.77	gold quality
cranial nerve II	UBERON:0000941	89.76	gold quality
postcentral gyrus	UBERON:0002581	89.60	gold quality
subthalamic nucleus	UBERON:0001906	89.58	gold quality
trabecular bone tissue	UBERON:0002483	89.40	gold quality
sural nerve	UBERON:0015488	89.32	gold quality
jejunal mucosa	UBERON:0000399	89.31	gold quality
parietal lobe	UBERON:0001872	89.18	gold quality
mucosa of urinary bladder	UBERON:0001259	89.10	gold quality
ventral tegmental area	UBERON:0002691	89.00	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-7407	yes	593.17
E-MTAB-5061	yes	272.38
E-MTAB-8142	yes	39.72
E-CURD-112	yes	11.66
E-ANND-3	yes	10.04
E-MTAB-9801	yes	7.83
E-GEOD-150728	no	3267.11
E-MTAB-2983	no	948.18
E-HCAD-6	no	721.78
E-CURD-46	no	5.18
E-MTAB-6678	no	4.10

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR3C1

miRNA regulators (miRDB)

195 targeting RPS6KA5, 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-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-548AJ-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 40)

• IL1beta and TNFalpha activation of MSK1 and CREB and cAMP-response element signaling cascades occurs via ERK/p38 MAP kinases and are crucial aspects of the intracellular mechanisms that mediate MUC5AC gene expression (PMID:12690113)
• acetylation of histones may stimulate transcription by suppressing an inhibitory phosphorylation by MSK1 (PMID:15010469)
• MSK1 has a role in transforming growth factor-beta-mediated responses through p38alpha and Smad signaling pathways (PMID:15133024)
• essential role of the C-terminal domain of MSK1 for its constitutive interaction with group V secretory phospholipase A(2), which appears essential to support VEGF-mediated PAF synthesis (PMID:16479592)
• Plays a positive role in the control of cell proliferation of both HaCaT keratinocytes and the A431 human epidermoid carcinoma line. (PMID:16532028)
• As MSK1 regulates the production of pro-inflammatory cytokines, it may play a role in the pathogenesis of psoriasis. (PMID:16543895)
• MSK1 has a role downstream of p38 in the regulation of As2O3 responses (PMID:16762916)
• Thr700 phosphorylation relieves the inhibition of MSK1 by a C-terminal autoinhibitory helix and helps induce a conformational shift that protects Thr581 from dephosphorylation (PMID:17117922)
• Dimethylfumarate specifically inhibits MSK1 and 2 activations and subsequently inhibits NF-kappaB-induced gene-transcriptions, which are believed to be important in the pathogenesis of psoriasis (PMID:17495961)
• the induction of inflammatory genes by farnesol is mediated by the activation of the NF-kappaB pathway and involves MEK1/2-ERK1/2-MSK1-dependent phosphorylation of p65/RelA(Ser(276)) (PMID:18424438)
• the action of 1,25(OH)(2)D(3) on colon carcinoma cells depends on the dual action of VDR as a transcription factor and a nongenomic activator of RhoA-ROCK and p38MAPK-MSK1. (PMID:19015318)
• This study provides therefore a direct link between MSK1-mediated phosphorylation of Ser276 p65 of NF-kappaB, allowing its binding to the SCF intronic enhancer, and pathophysiological SCF expression in inflammation. (PMID:19197368)
• IL-17F may be involved in airway inflammation and remodeling via the induction of IL-11, and RafI-MEK1/2-ERK1/2-MSK1-CREB is identified as a novel signaling pathway. (PMID:19251839)
• Data reveal that TPA activates transcription of TBX2 through activating MSK1, which leads to an increase in phosphorylated histone H3 and the recruitment of Sp1 to the TBX2 gene. (PMID:19633291)
• Data provide evidence that p38 Map kinase pathway is activated leading to increased upregulation of mixed lineage kinase 3, MKK3/6, MSK1, and Mapkapk2, upon treatment of BCR/ABL expressing cells with dasatinib. (PMID:19672773)
• We conclude that RSV induces RelA activation in the innate inflammatory response via a pathway separate from that controlling RelA cytoplasmic release, mediated by ROS signaling to cytoplasmic MSK1 activation and RelA Ser-276 phosphorylation. (PMID:19706715)
• MSK1 and MSK2 are differentially regulated by CK2 during the UV response and that MSK2 is the major protein kinase responsible for the UV-induced phosphorylation of p65 at Ser(276) that positively regulates NF-kappaB activity in MDA-MB-231 cells (PMID:19933278)
• The MSK1 can be phosphorylated and activated in cells by both ERK1/2 and p38alpha. (PMID:20044958)
• CREB controls MSK1-mediated phosphorylation of histone H3 at the c-fos promoter in vitro (PMID:20089855)
• Bile acid regulates MUC2 transcription in colon cancer cells via positive EGFR/PKC/Ras/ERK/CREB, PI3K/Akt/IkappaB/NF-kappaB and p38/MSK1/CREB pathways and negative JNK/c-Jun/AP-1 pathway. (PMID:20198339)
• MiR-148a attenuates paclitaxel resistance of hormone-refractory, drug-resistant prostate cancer PC3 cells by regulating MSK1 expression (PMID:20406806)
• In this study, by applying a novel method, we have identified the phosphorylation sites in human MSK1 mitogen- and stress-activated protein kinase 1, and show that MRK-beta could also activate MSK1 through direct interaction. (PMID:20408143)
• MSK1- and MSK2-mediated H3K27me3S28 phosphorylation serves as a mechanism to activate a subset of PcG target genes determined by the biological stimuli and thereby modulate the gene expression program determining cell fate. (PMID:20864036)
• MSK1 is a direct and potent transcriptional activator when targeted to c-fos promotor, and when targeted to alpha-globin promoter induces H3 S28 phosphorylation reactivating expression of this polycomb-silenced gene. (PMID:21282660)
• MSK1 is an important downstream kinase involved in CS-induced NF-kappaB activation (PMID:22312446)
• Astaxanthin attenuates the UVB-induced secretion of prostaglandin E2 and interleukin-8 in human keratinocytes by interrupting MSK1 phosphorylation in a ROS depletion-independent manner (PMID:22626465)
• MSK1 plays an important role for hormone-dependent breast cancer growth (PMID:23604116)
• Angiopoietin 2-mediated signaling via survivin/ref-1/MSK-1 pathway promotes doxorubicin resistance in HepG2 cells. (PMID:23643942)
• MSK1 and MSK2 are required for maximal TFF 1 induction. (PMID:23675462)
• Data suggest that MSK1 and MSK2 are the major CREB kinases in fibroblast-like synoviocytes from rheumatoid arthritis patients stimulated with lysophosphatidic acid and that phosphorylation of CREB1 at Ser-133 plays a significant role in IL-8 production. (PMID:24792438)
• These results highlight the relevance of MSK1 in the up-regulation of RARbeta by prostaglandin E2. (PMID:24953041)
• Authors conclude that paramyxoviruses trigger the DNA damage response, a pathway required for MSK1 activation of phospho Ser 276 RelA formation to trigger the IRF7-RIG-I amplification loop necessary for mucosal interferon production. (PMID:25520509)
• Increased MSK1 activity is critically important for Epstein-Barr virus LMP1-promoted cell proliferation and transformation. (PMID:25958199)
• Interrupting MSK1 activation is a new target for antioxidants. (PMID:26030901)
• KSHV activates the MSK1/2-CREB1 pathway during primary infection and that it depends on this pathway for viral lytic replication. I (PMID:26109721)
• Our findings indicate that MSK1/beta-catenin signaling serves as an escape survival signal upon PI3K inhibition and provides a strong rationale for the combined use of PI3K and MSK1/beta-catenin inhibition to induce lethal growth inhibition in human GBM cells. (PMID:27196759)
• Results show that MSK1 phosphorylates H3S10 through p38-MAPK pathway in gastric cancer patients. (PMID:27588146)
• MSK1 was overexpressed in 148 out of 329 colorectal cancer (CRC) patients. CRC patients with high MSK1 expression had shorter overall survival than those with low MSK1, especially among patients with stage III tumors. Overexpression of MSK1 is associated with poor prognosis in CRC and is connected to tumor aggressiveness. (PMID:28314603)
• High MSK1 is associated with improved breast cancer-specific survival in early stage invasive breast cancer patients, and has additional prognostic value in HER2-negative and non-basal like disease. (PMID:29327245)
• We show that MSK1 downregulation impairs the differentiation of breast cancer cells, increasing their bone homing and growth capacities. MSK1 controls the expression of genes required for luminal cell differentiation, including the GATA3 and FOXA1 transcription factors, by modulating their promoter chromatin status. (PMID:29358704)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	rps6ka5	ENSDARG00000060551
mus_musculus	Rps6ka5	ENSMUSG00000021180
rattus_norvegicus	Rps6ka5	ENSRNOG00000004362
drosophila_melanogaster	JIL-1	FBGN0020412
drosophila_melanogaster	S6k	FBGN0283472
caenorhabditis_elegans	rskn-2	WBGENE00008311
caenorhabditis_elegans		WBGENE00012929
caenorhabditis_elegans		WBGENE00017898
caenorhabditis_elegans		WBGENE00044281

Paralogs (7): RPS6KA2 (ENSG00000071242), RPS6KA6 (ENSG00000072133), RPS6KB1 (ENSG00000108443), RPS6KA1 (ENSG00000117676), RPS6KA4 (ENSG00000162302), RPS6KB2 (ENSG00000175634), RPS6KA3 (ENSG00000177189)

Protein

Protein identifiers

Ribosomal protein S6 kinase alpha-5 — O75582 (reviewed: O75582)

Alternative names: 90 kDa ribosomal protein S6 kinase 5, Nuclear mitogen- and stress-activated protein kinase 1, RSK-like protein kinase

All UniProt accessions (5): O75582, A0A3B3ISL8, G3V2D1, G3V4D7, H0YJE1

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factors RELA, STAT3 and ETV1/ER81, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF and upon glucocorticoid, associates in the cytoplasm with the glucocorticoid receptor NR3C1 and contributes to RELA inhibition and repression of inflammatory gene expression. In skeletal myoblasts is required for phosphorylation of RELA at ‘Ser-276’ during oxidative stress. In erythropoietin-stimulated cells, is necessary for the ‘Ser-727’ phosphorylation of STAT3 and regulation of its transcriptional potential. Phosphorylates ETV1/ER81 at ‘Ser-191’ and ‘Ser-216’, and thereby regulates its ability to stimulate transcription, which may be important during development and breast tumor formation. Directly represses transcription via phosphorylation of ‘Ser-1’ of histone H2A. Phosphorylates ‘Ser-10’ of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate ‘Ser-28’ of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors. Plays a role in neuronal cell death by mediating the downstream effects of excitotoxic injury. Phosphorylates TRIM7 at ‘Ser-107’ in response to growth factor signaling via the MEK/ERK pathway, thereby stimulating its ubiquitin ligase activity.

Subunit / interactions. Forms a complex with either MAPK1/ERK2 or MAPK3/ERK1 in quiescent cells which transiently dissociates following mitogenic stimulation. Also associates with MAPK14/p38-alpha. Activated RPS6KA5 associates with and phosphorylates the NF-kappa-B p65 subunit RELA. Interacts with CREBBP and EP300.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Widely expressed with high levels in heart, brain and placenta. Less abundant in lung, kidney and liver.

Post-translational modifications. Ser-376 and Thr-581 phosphorylation is required for kinase activity. Ser-376 and Ser-212 are autophosphorylated by the C-terminal kinase domain, and their phosphorylation is essential for the catalytic activity of the N-terminal kinase domain. Phosphorylated at Ser-360, Thr-581 and Thr-700 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha. Autophosphorylated at Ser-750, Ser-752 and Ser-758 by the N-terminal kinase domain. Ubiquitinated.

Activity regulation. Activated by phosphorylation at Ser-360, Thr-581 and Thr-700 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha, and by further autophosphorylation of Ser-212, Ser-376 and Ser-381 by the activated C-terminal kinase domain. The active N-terminal kinase domain finally phosphorylates downstream substrates, as well as Ser-750, Ser-752 and Ser-758 in its own C-terminal region.

Miscellaneous. Enzyme activity requires the presence of both kinase domains.

Similarity. Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
O75582-1	1	yes
O75582-2	2
O75582-3	3

RefSeq proteins (14): NP_001309156, NP_001309157, NP_001309158, NP_001309159, NP_001309160, NP_001309161, NP_001309162, NP_001309163, NP_001309164, NP_001309165, NP_001309166, NP_001309167, NP_004746, NP_872198 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR000961	AGC-kinase_C	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR016239	Ribosomal_S6_kinase_II	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR017892	Pkinase_C	Domain

Pfam: PF00069, PF00433

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 (105 total): helix 28, strand 22, modified residue 14, turn 8, mutagenesis site 7, binding site 4, sequence variant 4, sequence conflict 4, domain 3, splice variant 3, compositionally biased region 3, active site 2, region of interest 2, chain 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
1VZO	X-RAY DIFFRACTION	1.8
3KN6	X-RAY DIFFRACTION	2
3KN5	X-RAY DIFFRACTION	2.4
7UP6	X-RAY DIFFRACTION	2.6
7UP5	X-RAY DIFFRACTION	2.8
7UP7	X-RAY DIFFRACTION	2.8
7UP8	X-RAY DIFFRACTION	2.9
7UP4	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75582-F1	70.80	0.26

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 (2): 544 (proton acceptor); 177 (proton acceptor)

Ligand- & substrate-binding residues (4): 55–63; 81; 432–440; 455

Post-translational modifications (14): 212, 360, 376, 381, 581, 647, 657, 691, 695, 700, 750, 752, 758, 798

Mutagenesis-validated functional residues (7):

Position	Phenotype
195	loss of kinase activity.
212	inactivates the n-terminal kinase domain.
360	decreases kinase activity by 60% in response to pma and uv-c.
376	loss of kinase activity, and decreases the phosphorylation of s-360 and t-581.
565	loss of kinase activity.
581	loss of kinase activity, and blocks phosphorylation of s-212; s-376 and s-381 in response to pma and uv-c.
700	strongly reduces phosphorylation of t-581 in response to pma and uv-c.

Function

Pathways and Gene Ontology

Reactome pathways

38 pathways

ID	Pathway
R-HSA-198753	ERK/MAPK targets
R-HSA-199920	CREB phosphorylation
R-HSA-375165	NCAM signaling for neurite out-growth
R-HSA-437239	Recycling pathway of L1
R-HSA-5621575	CD209 (DC-SIGN) signaling
R-HSA-1266738	Developmental Biology
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-162582	Signal Transduction
R-HSA-166016	Toll Like Receptor 4 (TLR4) Cascade
R-HSA-166058	MyD88:MAL(TIRAP) cascade initiated on plasma membrane
R-HSA-166166	MyD88-independent TLR4 cascade
R-HSA-166520	Signaling by NTRKs
R-HSA-168138	Toll Like Receptor 9 (TLR9) Cascade
R-HSA-168142	Toll Like Receptor 10 (TLR10) Cascade
R-HSA-168164	Toll Like Receptor 3 (TLR3) Cascade
R-HSA-168176	Toll Like Receptor 5 (TLR5) Cascade
R-HSA-168179	Toll Like Receptor TLR1:TLR2 Cascade
R-HSA-168181	Toll Like Receptor 7/8 (TLR7/8) Cascade
R-HSA-168188	Toll Like Receptor TLR6:TLR2 Cascade
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-168898	Toll-like Receptor Cascades
R-HSA-181438	Toll Like Receptor 2 (TLR2) Cascade
R-HSA-187037	Signaling by NTRK1 (TRKA)
R-HSA-198725	Nuclear Events (kinase and transcription factor activation)
R-HSA-373760	L1CAM interactions
R-HSA-422475	Axon guidance
R-HSA-448424	Interleukin-17 signaling
R-HSA-449147	Signaling by Interleukins
R-HSA-450282	MAPK targets/ Nuclear events mediated by MAP kinases

MSigDB gene sets: 459 (showing top): E2F_Q4, MYAATNNNNNNNGGC_UNKNOWN, E2F_Q4_01, REACTOME_INNATE_IMMUNE_SYSTEM, TGCGCANK_UNKNOWN, E2F4DP1_01, MORF_MSH3, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_CREB_TRANSCRIPTION_FACTOR_ACTIVITY, MORF_BRCA1, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, REACTOME_NCAM_SIGNALING_FOR_NEURITE_OUT_GROWTH

GO Biological Process (15): negative regulation of cytokine production (GO:0001818), regulation of DNA-templated transcription (GO:0006355), protein phosphorylation (GO:0006468), inflammatory response (GO:0006954), axon guidance (GO:0007411), obsolete positive regulation of CREB transcription factor activity (GO:0032793), intracellular signal transduction (GO:0035556), TORC1 signaling (GO:0038202), post-translational protein modification (GO:0043687), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), interleukin-1-mediated signaling pathway (GO:0070498), regulation of postsynapse organization (GO:0099175), chromatin remodeling (GO:0006338)

GO Molecular Function (14): magnesium ion binding (GO:0000287), protein serine/threonine kinase activity (GO:0004674), protein tyrosine kinase activity (GO:0004713), ATP binding (GO:0005524), histone H3S10 kinase activity (GO:0035175), histone H3S28 kinase activity (GO:0044022), histone H2AS1 kinase activity (GO:0044024), 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), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Toll-like Receptor Cascades	6
Nuclear Events (kinase and transcription factor activation)	2
MAPK targets/ Nuclear events mediated by MAP kinases	2
Immune System	2
Toll Like Receptor 4 (TLR4) Cascade	2
Toll Like Receptor 2 (TLR2) Cascade	2
Axon guidance	1
L1CAM interactions	1
C-type lectin receptors (CLRs)	1
Toll Like Receptor TLR1:TLR2 Cascade	1
Toll Like Receptor TLR6:TLR2 Cascade	1
Signaling by Receptor Tyrosine Kinases	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	3
protein serine/threonine kinase activity	3
DNA-templated transcription	2
protein modification process	2
intracellular anatomical structure	2
histone H3 kinase activity	2
cellular anatomical structure	2
cytokine production	1
regulation of cytokine production	1
negative regulation of gene expression	1
negative regulation of multicellular organismal process	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
phosphorylation	1
defense response	1
axonogenesis	1
neuron projection guidance	1
signal transduction	1
TOR signaling	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
cytokine-mediated signaling pathway	1
cellular response to interleukin-1	1
regulation of synapse organization	1
postsynapse organization	1
chromatin organization	1
metal ion binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
histone H2A kinase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1

Protein interactions and networks

STRING

1128 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPS6KA5	ATF1	P18846	783
RPS6KA5	CREB1	P16220	702
RPS6KA5	EP300	Q09472	602
RPS6KA5	YWHAZ	P29213	600
RPS6KA5	H3C1	P02295	586
RPS6KA5	H3-7	Q5TEC6	586
RPS6KA5	H3C14	Q71DI3	585
RPS6KA5	H3-5	Q6NXT2	585
RPS6KA5	H3-4	Q16695	585
RPS6KA5	H3-3A	P06351	584
RPS6KA5	SMARCA4	P51532	517
RPS6KA5	EZH2	Q15910	512
RPS6KA5	PGR	P06401	500
RPS6KA5	CD58	P19256	500
RPS6KA5	JUN	P05412	481

IntAct

75 interactions, top by confidence:

A	B	Type	Score
MAPK14	OBSL1	psi-mi:“MI:0914”(association)	0.790
RPS6KA5	CSNK2B	psi-mi:“MI:0915”(physical association)	0.660
CSNK2B	RPS6KA5	psi-mi:“MI:0914”(association)	0.660
MAPK14	RPS6KA5	psi-mi:“MI:0914”(association)	0.660
CHCHD4	SSNA1	psi-mi:“MI:0914”(association)	0.640
MAP3K20	RPS6KA5	psi-mi:“MI:0915”(physical association)	0.600
RPS6KA5	MAP3K20	psi-mi:“MI:0915”(physical association)	0.600
RPS6KA5	MAP3K20	psi-mi:“MI:0403”(colocalization)	0.600
RPS6KA5	CTNNA3	psi-mi:“MI:0915”(physical association)	0.560
RPS6KA5	RELA	psi-mi:“MI:2364”(proximity)	0.540
RELA	RPS6KA5	psi-mi:“MI:0915”(physical association)	0.540
CLEC4A	SEMA7A	psi-mi:“MI:0914”(association)	0.530
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
LAMP3	METTL15	psi-mi:“MI:0914”(association)	0.530
KDM3A	RPS6KA5	psi-mi:“MI:0915”(physical association)	0.520
	RPS6KA5	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
RPS6KA5	MAPT	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
RPS6KA5	PKM	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
RPS6KA5	HSP90AA4P	psi-mi:“MI:0915”(physical association)	0.400
RPS6KA5	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
RPS6KA5	NR3C1	psi-mi:“MI:0915”(physical association)	0.400
RPA1	RPS6KA5	psi-mi:“MI:0915”(physical association)	0.370
RPS6KA5	IL17RB	psi-mi:“MI:0915”(physical association)	0.370
RPS6KA5	ALG8	psi-mi:“MI:0915”(physical association)	0.370
RPS6KA5	GPRASP2	psi-mi:“MI:0915”(physical association)	0.370
FN1	RPS6KA5	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (145): RPS6KA5 (Affinity Capture-MS), HIST1H2BB (Biochemical Activity), MBP (Biochemical Activity), HIST1H1A (Biochemical Activity), RPS6KA5 (Co-localization), RELA (Co-localization), EGF (Co-localization), ATF2 (Co-localization), ATF1 (Biochemical Activity), MAPK14 (Reconstituted Complex), RPS6KA5 (Affinity Capture-MS), HSP90AA4P (Affinity Capture-MS), RPS6KA5 (Affinity Capture-RNA), RPS6KA5 (Synthetic Lethality), MAPK1 (Phenotypic Enhancement)

ESM2 similar proteins: A2VDV2, A8XJL7, O13310, O75582, O97627, P00518, P07934, P13286, P18652, P18653, P18654, P21146, P23443, P26817, P26818, P26819, P35626, P51812, P54645, P67998, P67999, Q09639, Q12706, Q15208, Q21734, Q2L6W9, Q2LZZ7, Q39030, Q3UYH7, Q54IH8, Q5F3L1, Q5R4K3, Q5R8M1, Q64682, Q6PFQ0, Q6TGC6, Q6TJY3, Q7TPS0, Q7TSE6, Q8BGW6

Diamond homologs: A1Z9X0, A2YBX5, F1M7Y5, F4HPN2, F4HYG2, F4I4F2, F4J6F6, O13310, O15021, O42626, O48963, O60307, O64682, O75582, O75676, P09217, P10666, P15792, P18652, P18654, P25341, P28178, P31034, P34099, P34102, P34103, P38938, P41743, P42818, P47197, P51812, P51817, P53739, P53894, P93025, Q02956, Q05513, Q05999, Q09831, Q0DCT8

SIGNOR signaling

62 interactions.

A	Effect	B	Mechanism
RPS6KA5	up-regulates	STAT3	phosphorylation
MAPK1	up-regulates	RPS6KA5	phosphorylation
RPS6KA5	“down-regulates activity”	H3-3A	phosphorylation
RPS6KA5	“down-regulates activity”	H3C1	phosphorylation
RPS6KA5	up-regulates	H2AC11	phosphorylation
MAPK14	“up-regulates activity”	RPS6KA5	phosphorylation
MAPK3	up-regulates	RPS6KA5	phosphorylation
RPS6KA5	“up-regulates activity”	RPS6KA5	phosphorylation
RPS6KA5	unknown	RPS6KA5	phosphorylation
RPS6KA5	“up-regulates activity”	H3-3A	phosphorylation
RPS6KA5	up-regulates	NfKb-p65/p50	phosphorylation
RPS6KA5	“up-regulates activity”	PLA2G4A	phosphorylation
RPS6KA5	unknown	NR4A1	phosphorylation
ERK1/2	up-regulates	RPS6KA5	phosphorylation
ERK1/2	“up-regulates activity”	RPS6KA5	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 72 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
Interleukin-17 signaling	5	25.9×	3e-04
Toll Like Receptor 10 (TLR10) Cascade	5	22.0×	3e-04
Toll Like Receptor 5 (TLR5) Cascade	5	22.0×	3e-04
MyD88 cascade initiated on plasma membrane	5	20.8×	3e-04
Toll Like Receptor 3 (TLR3) Cascade	5	19.8×	3e-04
TRIF (TICAM1)-mediated TLR4 signaling	5	19.4×	3e-04
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	5	19.4×	3e-04
MyD88 dependent cascade initiated on endosome	5	19.4×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	76
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4668 predictions. Top by Δscore:

Variant	Effect	Δscore
14:90875195:TCTTA:T	donor_loss	1.0000
14:90875196:CTTAC:C	donor_loss	1.0000
14:90875197:TTA:T	donor_loss	1.0000
14:90875198:TACC:T	donor_loss	1.0000
14:90875361:C:CC	acceptor_gain	1.0000
14:90875365:C:CT	acceptor_gain	1.0000
14:90890482:CTCA:C	donor_loss	1.0000
14:90890483:TCAC:T	donor_loss	1.0000
14:90890484:CAC:C	donor_loss	1.0000
14:90890485:A:AC	donor_gain	1.0000
14:90890485:A:T	donor_loss	1.0000
14:90890486:C:CT	donor_gain	1.0000
14:90890486:CCAAA:C	donor_gain	1.0000
14:90890614:CG:C	acceptor_gain	1.0000
14:90890615:G:C	acceptor_gain	1.0000
14:90890674:AAATT:A	acceptor_gain	1.0000
14:90890675:AATT:A	acceptor_gain	1.0000
14:90890676:ATTC:A	acceptor_loss	1.0000
14:90890677:TT:T	acceptor_gain	1.0000
14:90890677:TTC:T	acceptor_loss	1.0000
14:90890678:TC:T	acceptor_loss	1.0000
14:90890679:C:CA	acceptor_loss	1.0000
14:90890679:C:CC	acceptor_gain	1.0000
14:90890680:T:A	acceptor_loss	1.0000
14:90894407:TTATA:T	donor_loss	1.0000
14:90894408:TATA:T	donor_loss	1.0000
14:90894409:ATAC:A	donor_loss	1.0000
14:90894410:TACCT:T	donor_loss	1.0000
14:90894411:A:AT	donor_loss	1.0000
14:90894462:A:AC	donor_gain	1.0000

AlphaMissense

5334 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:90872251:T:A	R744S	1.000
14:90872251:T:G	R744S	1.000
14:90872252:C:G	R744T	1.000
14:90872254:T:A	R743S	1.000
14:90872254:T:G	R743S	1.000
14:90872255:C:G	R743T	1.000
14:90873736:A:G	W686R	1.000
14:90873736:A:T	W686R	1.000
14:90873767:C:A	R675S	1.000
14:90873767:C:G	R675S	1.000
14:90873768:C:A	R675M	1.000
14:90873768:C:G	R675T	1.000
14:90873789:A:G	L668P	1.000
14:90873792:A:G	L667P	1.000
14:90875240:A:G	W653R	1.000
14:90875240:A:T	W653R	1.000
14:90890497:C:T	G609D	1.000
14:90890498:C:G	G609R	1.000
14:90890505:C:A	W606C	1.000
14:90890505:C:G	W606C	1.000
14:90890507:A:G	W606R	1.000
14:90890507:A:T	W606R	1.000
14:90890623:C:T	G567E	1.000
14:90890628:A:C	D565E	1.000
14:90890628:A:T	D565E	1.000
14:90890629:T:A	D565V	1.000
14:90890629:T:C	D565G	1.000
14:90890629:T:G	D565A	1.000
14:90890630:C:G	D565H	1.000
14:90890676:A:C	N549K	1.000

dbSNP variants (sampled 300 via entrez): RS1000001221 (14:91015340 T>C), RS1000005254 (14:91037749 G>C), RS1000009092 (14:90956169 T>C,G), RS1000037221 (14:91057365 T>A), RS1000066331 (14:90907742 G>A,C), RS1000074301 (14:91036355 C>A,G,T), RS1000076188 (14:91029472 T>C), RS1000091206 (14:91000759 G>A), RS1000105359 (14:90903749 C>T), RS1000115997 (14:90936617 A>C), RS1000122676 (14:91012101 T>C), RS1000161743 (14:90879228 T>C,G), RS1000169209 (14:91004749 C>T), RS1000194933 (14:90877208 T>C), RS1000217309 (14:91021427 G>A,C)

Disease associations

OMIM: gene MIM:603607 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

23 associations (top):

Study	Trait	p-value
GCST004097_2	Response to platinum-based neoadjuvant chemotherapy in cervical cancer	7.000000e-06
GCST005795_36	Femoral neck bone mineral density	4.000000e-08
GCST005796_24	Lumbar spine bone mineral density	6.000000e-12
GCST005956_47	Waist-to-hip ratio adjusted for BMI	7.000000e-07
GCST005962_28	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	7.000000e-07
GCST006423_12	Fracture	2.000000e-17
GCST006979_1012	Heel bone mineral density	2.000000e-36
GCST007691_32	Femoral neck bone mineral density	2.000000e-15
GCST008522_92	Bitter alcoholic beverage consumption	8.000000e-06
GCST009597_213	Multiple sclerosis	8.000000e-06
GCST010916_23	Proportion of activated microglia (inferior temporal cortex)	7.000000e-06
GCST010988_543	Adult body size	8.000000e-10
GCST90013406_110	Liver enzyme levels (alkaline phosphatase)	3.000000e-12
GCST90020024_474	A body shape index	5.000000e-08
GCST90020024_773	A body shape index	3.000000e-10
GCST90020025_430	Waist-to-hip ratio adjusted for BMI	1.000000e-14
GCST90020025_431	Waist-to-hip ratio adjusted for BMI	2.000000e-13
GCST90020026_239	Hip index	8.000000e-09
GCST90020026_240	Hip index	2.000000e-10
GCST90020027_683	Waist-hip index	3.000000e-15
GCST90020027_684	Waist-hip index	1.000000e-13
GCST90020028_1871	Hip circumference adjusted for BMI	2.000000e-09
GCST90020029_400	Waist circumference adjusted for body mass index	4.000000e-09

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0007943	response to platinum-based neoadjuvant chemotherapy
EFO:0007785	femoral neck bone mineral density
EFO:0007701	spine bone mineral density
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0009270	heel bone mineral density
EFO:0010092	bitter alcoholic beverage consumption measurement
EFO:0004533	alkaline phosphatase measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3832633 (PROTEIN FAMILY), CHEMBL4237 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

25 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 170,788 (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
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL274654	ORANTINIB	3	3,596
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL38380	FASUDIL	3	11,953
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL1721885	SU-014813	2	363
CHEMBL1980297	ILORASERTIB	2	581
CHEMBL475251	R-406	2	762
CHEMBL495727	AT-9283	2	1,376
CHEMBL513909	BI-2536	2	895
CHEMBL3544960	AT-13148	1	779
CHEMBL1908397	KW-2449	1	622
CHEMBL2140408	AMG-900	1
CHEMBL296468	BMS-387032	1
CHEMBL3128043	PF-03758309	1
CHEMBL494089	GSK-690693	1
CHEMBL574738	AST-487	1

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — MSK subfamily

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
SB-747651A	Inhibition	9.3	pIC50
compound 24 [PMID: 15955699]	Inhibition	8.85	pIC50
compound 23 [PMID: 35816678]	Inhibition	6.84	pIC50

Binding affinities (BindingDB)

23 measured of 24 human assays (24 total across all organisms); most potent 23 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Staurosporine	KD	1.7 nM
4-[2-(4-amino-1,2,5-oxadiazol-3-yl)-7-(3-aminopropoxy)-1-ethyl-1H-imidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol	IC50	6 nM
Pyrrolopyridine, 16	IC50	8.5 nM
JMC502647 Compound 8	IC50	10 nM
4-[1-ethyl-7-(piperidin-4-ylmethoxy)-1H-imidazo[4,5-c]pyridin-2-yl]-1,2,5-oxadiazol-3-amine	IC50	56 nM
Pyrrolopyridine, 9	IC50	66 nM
4-[1-ethyl-7-(piperidin-4-yloxy)-1H-imidazo[4,5-c]pyridin-2-yl]-1,2,5-oxadiazol-3-amine	IC50	79 nM
4-[7-(3-aminopropoxy)-1-ethyl-4-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl]-1,2,5-oxadiazol-3-amine	IC50	79 nM
2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-N-[2-(methylamino)ethyl]-1H-imidazo[4,5-c]pyridine-7-carboxamide	IC50	126 nM
Pyrrolopyridine, 23	IC50	126 nM
PKC-412	KD	190 nM
4-{1-ethyl-7-[(piperidin-4-ylamino)methyl]-1H-imidazo[4,5-c]pyridin-2-yl}-1,2,5-oxadiazol-3-amine	IC50	200 nM
4-(7-{[(3R)-3-aminopyrrolidin-1-yl]carbonyl}-1-ethyl-1H-imidazo[4,5-c]pyridin-2-yl)-1,2,5-oxadiazol-3-amine	IC50	331 nM
4-[7-(3-aminopropoxy)-1-ethyl-4-phenyl-1H-imidazo[4,5-c]pyridin-2-yl]-1,2,5-oxadiazol-3-amine	IC50	331 nM
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methyl-phenyl)urea	KD	450 nM
4-[1-ethyl-7-(piperazin-1-ylcarbonyl)-1H-imidazo[4,5-c]pyridin-2-yl]-1,2,5-oxadiazol-3-amine	IC50	501 nM
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril	KD	520 nM
2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-N-(piperidin-4-yl)-1H-imidazo[4,5-c]pyridine-7-carboxamide	IC50	562 nM
2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-N-(piperidin-3-yl)-1H-imidazo[4,5-c]pyridine-7-carboxamide	IC50	631 nM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.1^{7,14}.0^{2,6}.0^{8,13}.0^{22,27}]nonacosa-1(28),2(6),7(29),8(13),9,11,22(27),23,25-nonaene-3,5-dione	KD	700 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 nM
5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamide	KD	2600 nM
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	KD	3500 nM

ChEMBL bioactivities

332 potent at pChembl≥5 of 345 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.60	IC50	0.2512	nM	CHEMBL5177437
9.37	IC50	0.426	nM	STAUROSPORINE
9.30	IC50	0.5	nM	CHEMBL188434
9.26	IC50	0.553	nM	STAUROSPORINE
9.20	IC50	0.631	nM	CHEMBL5178687
9.10	Ki	0.7943	nM	CHEMBL1970903
9.00	IC50	1	nM	CHEMBL521823
8.90	Ki	1.259	nM	CHEMBL1991063
8.85	IC50	1.4	nM	CHEMBL415770
8.85	IC50	1.4	nM	STAUROSPORINE
8.85	IC50	1.42	nM	STAUROSPORINE
8.82	IC50	1.5	nM	CHEMBL185962
8.74	IC50	1.8	nM	CHEMBL185962
8.70	IC50	2	nM	CHEMBL188806
8.60	IC50	2.5	nM	CHEMBL186317
8.52	IC50	3	nM	CHEMBL189657
8.52	IC50	3	nM	CHEMBL189231
8.52	IC50	3	nM	CHEMBL426440
8.52	IC50	3	nM	CHEMBL523695
8.42	IC50	3.79	nM	CHEMBL3909070
8.40	IC50	4	nM	CHEMBL2347053
8.40	IC50	4	nM	CHEMBL187340
8.40	IC50	4	nM	CHEMBL188268
8.30	IC50	5.012	nM	CHEMBL5178687
8.30	Ki	5.012	nM	CHEMBL1974870
8.30	Ki	5.012	nM	CHEMBL1979883
8.28	Kd	5.3	nM	CHEMBL2023845
8.22	IC50	6	nM	CHEMBL188433
8.20	IC50	6.31	nM	CHEMBL4792347
8.15	IC50	7	nM	CHEMBL360219
8.12	IC50	7.58	nM	CHEMBL3927587
8.10	IC50	8	nM	CHEMBL364413
8.10	IC50	8	nM	CHEMBL188434
8.10	IC50	7.943	nM	CHEMBL5278787
8.10	IC50	8	nM	BISINDOLYLMALEIMIDE IX
8.10	Ki	7.943	nM	CHEMBL1990254
8.05	IC50	9	nM	CHEMBL188620
8.05	IC50	9	nM	CHEMBL365832
8.00	IC50	10	nM	CHEMBL5190298
7.99	IC50	10.3	nM	CHEMBL3924878
7.96	IC50	11	nM	CHEMBL188433
7.96	IC50	11	nM	CHEMBL493067
7.92	Kd	12	nM	CHEMBL2023841
7.92	IC50	12	nM	AT-13148
7.90	IC50	12.7	nM	CHEMBL3911801
7.90	IC50	12.59	nM	CHEMBL5184056
7.89	IC50	13	nM	CHEMBL188457
7.89	IC50	13	nM	CHEMBL363258
7.89	IC50	13	nM	CHEMBL494662
7.85	IC50	14	nM	CHEMBL1956071

PubChem BioAssay actives

206 with measured affinity, of 2474 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
(E)-2-cyano-3-[3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl]prop-2-enamide	1893503: Inhibition of full-length N-terminal His-TEV-tagged inactive form of MSK1 (2 to 802 residues) (unknown origin) expressed in HEK293 cells using FAM-PSKPAATRKRRWSAPESR-NH2 as substrate preincubated for 1 hr followed by activation with ERK2 and substrate addition measured after 2 hrs by microfluidic chip based electrophoresis	ic50	0.0003	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1715258: Inhibition of human MSK1 using GRPRTSSFAEG as substrate by [gamma-33P]-ATP assay	ic50	0.0004	uM
4-[1-ethyl-7-[(piperidin-4-ylamino)methyl]imidazo[4,5-c]pyridin-2-yl]-1,2,5-oxadiazol-3-amine	1933325: Inhibition of MSK-1 (unknown origin)	ic50	0.0005	uM
(E)-2-cyano-N-(1-hydroxy-2-methylpropan-2-yl)-3-[3-(3,4,5-trimethoxyphenyl)-1H-indazol-5-yl]prop-2-enamide	1893515: Inhibition of N-terminal His-Smt-tagged MSK1 C-terminal kinase domain (414 to 738 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) using FAM-PSKPAATRKRRWSAPESR-NH2 as substrate preincubated for 1 hr followed by substrate addition and measured after 70 mins by ADP-Glo kinase assay	ic50	0.0006	uM
4-[1-ethyl-7-(piperidin-4-ylmethoxy)imidazo[4,5-c]pyridin-2-yl]-1,2,5-oxadiazol-3-amine	1798494: In Vitro Kinase Inhibition Assay from Article 10.1021/jm8004527: “Identification of 4-(2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-{[(3S)-3-piperidinylmethyl]oxy}-1H-imidazo[4,5-c]pyridin-4-yl)-2-methyl-3-butyn-2-ol (GSK690693), a novel inhibitor of AKT kinase.”	ic50	0.0010	uM
4-[1-ethyl-7-(piperazin-1-ylmethyl)imidazo[4,5-c]pyridin-2-yl]-1,2,5-oxadiazol-3-amine	240472: Inhibitory concentration against MSK-1	ic50	0.0014	uM
4-(1-cyclopropylimidazo[4,5-c]pyridin-2-yl)-1,2,5-oxadiazol-3-amine	240472: Inhibitory concentration against MSK-1	ic50	0.0015	uM
4-(1-piperidin-3-ylimidazo[4,5-c]pyridin-2-yl)-1,2,5-oxadiazol-3-amine	240472: Inhibitory concentration against MSK-1	ic50	0.0020	uM
4-[1-[3-(aminomethyl)phenyl]imidazo[4,5-c]pyridin-2-yl]-1,2,5-oxadiazol-3-amine	240472: Inhibitory concentration against MSK-1	ic50	0.0025	uM
4-(1-ethylimidazo[4,5-c]pyridin-2-yl)-1,2,5-oxadiazol-3-amine	1933325: Inhibition of MSK-1 (unknown origin)	ic50	0.0030	uM
[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethylimidazo[4,5-c]pyridin-7-yl]-[(3R)-3-aminopyrrolidin-1-yl]methanone	1798494: In Vitro Kinase Inhibition Assay from Article 10.1021/jm8004527: “Identification of 4-(2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-{[(3S)-3-piperidinylmethyl]oxy}-1H-imidazo[4,5-c]pyridin-4-yl)-2-methyl-3-butyn-2-ol (GSK690693), a novel inhibitor of AKT kinase.”	ic50	0.0030	uM
4-(1-cyclohexylimidazo[4,5-c]pyridin-2-yl)-1,2,5-oxadiazol-3-amine	240472: Inhibitory concentration against MSK-1	ic50	0.0030	uM
4-[7-[(4-aminopiperidin-1-yl)methyl]-1-ethylimidazo[4,5-c]pyridin-2-yl]-1,2,5-oxadiazol-3-amine	240472: Inhibitory concentration against MSK-1	ic50	0.0030	uM
4-(4-chloro-1-ethylimidazo[4,5-c]pyridin-2-yl)-1,2,5-oxadiazol-3-amine	240472: Inhibitory concentration against MSK-1	ic50	0.0040	uM
4-[1-[4-(aminomethyl)phenyl]imidazo[4,5-c]pyridin-2-yl]-1,2,5-oxadiazol-3-amine	240472: Inhibitory concentration against MSK-1	ic50	0.0040	uM
(3Z)-3-[[5-(2-nitrophenyl)-1H-pyrazol-4-yl]methylidene]-1H-indol-2-one	739297: Inhibition of MSK1 (unknown origin) after 10 mins by mobility shift assay	ic50	0.0040	uM
3-[[(2R)-6-amino-1-[[N-[(4R)-5-amino-4-[[(2R)-5-carbamimidamido-2-[[(2R)-5-carbamimidamido-2-[[(2R)-5-carbamimidamido-2-[[(2R)-5-carbamimidamido-2-[[(2R)-5-carbamimidamido-2-[6-[2-(isoquinolin-5-ylsulfonylamino)ethylamino]hexanoylamino]pentanoyl]amino]pentanoyl]amino]pentanoyl]amino]pentanoyl]amino]pentanoyl]amino]-5-oxopentyl]carbamimidoyl]amino]-1-oxohexan-2-yl]carbamoyl]-4-[3,6-bis(dimethylamino)-3H-xanthen-9-yl]benzoic acid	659377: Binding affinity to His6-tagged recombinant human MSK1 by fluorescence anisotropy assay	kd	0.0053	uM
4-(1-phenylimidazo[4,5-c]pyridin-2-yl)-1,2,5-oxadiazol-3-amine	240472: Inhibitory concentration against MSK-1	ic50	0.0060	uM
N-cyclopropyl-4-methyl-3-[3-[2-[2-[2-(methylamino)ethoxy]phenyl]propan-2-ylamino]-2-oxopyrazin-1-yl]benzamide	1721565: Inhibition of human MSK1	ic50	0.0063	uM
4-[1-ethyl-7-(piperidin-1-ylmethyl)imidazo[4,5-c]pyridin-2-yl]-1,2,5-oxadiazol-3-amine	240472: Inhibitory concentration against MSK-1	ic50	0.0070	uM
N-[(1S)-2-amino-1-phenylethyl]-4-pyridin-4-ylbenzamide	1948867: Inhibition of RPS6KA5 (unknown origin)	ic50	0.0079	uM
4-(1-ethyl-4-methylimidazo[4,5-c]pyridin-2-yl)-1,2,5-oxadiazol-3-amine	240472: Inhibitory concentration against MSK-1	ic50	0.0080	uM
3-[3-[4-(1-methylindol-3-yl)-2,5-dioxopyrrol-3-yl]indol-1-yl]propyl carbamimidothioate	512454: Inhibition of His-tagged human MSK1 expressed in Sf9 cells	ic50	0.0080	uM
4-(7-bromo-1-ethylimidazo[4,5-c]pyridin-2-yl)-1,2,5-oxadiazol-3-amine	240472: Inhibitory concentration against MSK-1	ic50	0.0090	uM
4-[1-(1-aminopropan-2-yl)imidazo[4,5-c]pyridin-2-yl]-1,2,5-oxadiazol-3-amine	240472: Inhibitory concentration against MSK-1	ic50	0.0090	uM
5-(4-chloropyrimidin-2-yl)pyrrolo[3,2-d]pyrimidine	1893503: Inhibition of full-length N-terminal His-TEV-tagged inactive form of MSK1 (2 to 802 residues) (unknown origin) expressed in HEK293 cells using FAM-PSKPAATRKRRWSAPESR-NH2 as substrate preincubated for 1 hr followed by activation with ERK2 and substrate addition measured after 2 hrs by microfluidic chip based electrophoresis	ic50	0.0100	uM
2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-N-piperidin-3-ylimidazo[4,5-c]pyridine-7-carboxamide	1798494: In Vitro Kinase Inhibition Assay from Article 10.1021/jm8004527: “Identification of 4-(2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-{[(3S)-3-piperidinylmethyl]oxy}-1H-imidazo[4,5-c]pyridin-4-yl)-2-methyl-3-butyn-2-ol (GSK690693), a novel inhibitor of AKT kinase.”	ic50	0.0110	uM
N-[(2R)-1-[[6-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-amino-6-[[2-[24-(hydroxy-methylidene-oxo-lambda6-sulfanyl)-5,5,27,27-tetramethyl-16-oxa-12-aza-20-azoniaheptacyclo[15.11.0.03,15.04,12.06,11.020,28.021,26]octacosa-1,3,6(11),7,9,20(28),21(26),22,24-nonaen-8-yl]acetyl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-6-oxohexyl]amino]-5-carbamimidamido-1-oxopentan-2-yl]-8-[2-(isoquinolin-5-ylsulfonylamino)ethylamino]octanamide	659377: Binding affinity to His6-tagged recombinant human MSK1 by fluorescence anisotropy assay	kd	0.0120	uM
6-chloro-2-pyrrolo[3,2-d]pyrimidin-5-ylpyridine-3-carbonitrile	1893503: Inhibition of full-length N-terminal His-TEV-tagged inactive form of MSK1 (2 to 802 residues) (unknown origin) expressed in HEK293 cells using FAM-PSKPAATRKRRWSAPESR-NH2 as substrate preincubated for 1 hr followed by activation with ERK2 and substrate addition measured after 2 hrs by microfluidic chip based electrophoresis	ic50	0.0126	uM
2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-N-piperidin-4-ylimidazo[4,5-c]pyridine-7-carboxamide	1798494: In Vitro Kinase Inhibition Assay from Article 10.1021/jm8004527: “Identification of 4-(2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-{[(3S)-3-piperidinylmethyl]oxy}-1H-imidazo[4,5-c]pyridin-4-yl)-2-methyl-3-butyn-2-ol (GSK690693), a novel inhibitor of AKT kinase.”	ic50	0.0130	uM
4-[1-(1-aminobutyl)imidazo[4,5-c]pyridin-2-yl]-1,2,5-oxadiazol-3-amine	240487: Inhibitory concentration exhibited towards MSK-1	ic50	0.0130	uM
4-[1-(4-aminobutyl)imidazo[4,5-c]pyridin-2-yl]-1,2,5-oxadiazol-3-amine	240472: Inhibitory concentration against MSK-1	ic50	0.0130	uM
[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethylimidazo[4,5-c]pyridin-7-yl]-[(3S)-3-aminopyrrolidin-1-yl]methanone	649971: Inhibition of MSK1	ic50	0.0140	uM
2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-N-[2-(methylamino)ethyl]imidazo[4,5-c]pyridine-7-carboxamide	1798494: In Vitro Kinase Inhibition Assay from Article 10.1021/jm8004527: “Identification of 4-(2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-{[(3S)-3-piperidinylmethyl]oxy}-1H-imidazo[4,5-c]pyridin-4-yl)-2-methyl-3-butyn-2-ol (GSK690693), a novel inhibitor of AKT kinase.”	ic50	0.0150	uM
2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethylbenzimidazol-5-ol	240487: Inhibitory concentration exhibited towards MSK-1	ic50	0.0170	uM
4-(1-piperidin-4-ylimidazo[4,5-c]pyridin-2-yl)-1,2,5-oxadiazol-3-amine	240472: Inhibitory concentration against MSK-1	ic50	0.0170	uM
Sunitinib	508073: Binding affinity to RPS6KA2(Kin.Dom.1-N-terminal)	kd	0.0170	uM
1-(5-chloro-2-fluoropyrimidin-4-yl)pyrrolo[3,2-b]pyridine	1893503: Inhibition of full-length N-terminal His-TEV-tagged inactive form of MSK1 (2 to 802 residues) (unknown origin) expressed in HEK293 cells using FAM-PSKPAATRKRRWSAPESR-NH2 as substrate preincubated for 1 hr followed by activation with ERK2 and substrate addition measured after 2 hrs by microfluidic chip based electrophoresis	ic50	0.0199	uM
5-(2,5-dichloropyrimidin-4-yl)-7H-pyrrolo[2,3-d]pyrimidine	1893503: Inhibition of full-length N-terminal His-TEV-tagged inactive form of MSK1 (2 to 802 residues) (unknown origin) expressed in HEK293 cells using FAM-PSKPAATRKRRWSAPESR-NH2 as substrate preincubated for 1 hr followed by activation with ERK2 and substrate addition measured after 2 hrs by microfluidic chip based electrophoresis	ic50	0.0199	uM
3-(1-ethylimidazo[4,5-c]pyridin-2-yl)pyrazin-2-amine	1933325: Inhibition of MSK-1 (unknown origin)	ic50	0.0200	uM
4-(1-ethyl-7-piperidin-4-yloxyimidazo[4,5-c]pyridin-2-yl)-1,2,5-oxadiazol-3-amine	1798494: In Vitro Kinase Inhibition Assay from Article 10.1021/jm8004527: “Identification of 4-(2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-{[(3S)-3-piperidinylmethyl]oxy}-1H-imidazo[4,5-c]pyridin-4-yl)-2-methyl-3-butyn-2-ol (GSK690693), a novel inhibitor of AKT kinase.”	ic50	0.0210	uM
4-[1-(3-aminopropyl)imidazo[4,5-c]pyridin-2-yl]-1,2,5-oxadiazol-3-amine	240472: Inhibitory concentration against MSK-1	ic50	0.0220	uM
N-[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-6-[2-(isoquinolin-5-ylsulfonylamino)ethylamino]hexanamide	659387: Displacement of fluorescent-ARC-583/ARC-1042/ARC-1059 from His6-tagged recombinant human MSK1 by fluorescence anisotropy assay	kd	0.0260	uM
N-[2-hydroxy-3-[C-phenyl-N-[4-(piperidin-1-ylmethyl)phenyl]carbonimidoyl]-1H-indol-5-yl]ethanesulfonamide	389045: Binding affinity to human MSK1	kd	0.0310	uM
5-(5-bromo-2-chloropyrimidin-4-yl)pyrrolo[3,2-d]pyrimidine	1893503: Inhibition of full-length N-terminal His-TEV-tagged inactive form of MSK1 (2 to 802 residues) (unknown origin) expressed in HEK293 cells using FAM-PSKPAATRKRRWSAPESR-NH2 as substrate preincubated for 1 hr followed by activation with ERK2 and substrate addition measured after 2 hrs by microfluidic chip based electrophoresis	ic50	0.0316	uM
5-(2,5-dichloropyrimidin-4-yl)pyrrolo[3,2-d]pyrimidine	1893503: Inhibition of full-length N-terminal His-TEV-tagged inactive form of MSK1 (2 to 802 residues) (unknown origin) expressed in HEK293 cells using FAM-PSKPAATRKRRWSAPESR-NH2 as substrate preincubated for 1 hr followed by activation with ERK2 and substrate addition measured after 2 hrs by microfluidic chip based electrophoresis	ic50	0.0316	uM
4-(1-ethyl-5-fluorobenzimidazol-2-yl)-1,2,5-oxadiazol-3-amine	240487: Inhibitory concentration exhibited towards MSK-1	ic50	0.0380	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	624736: Binding constant for RPS6KA5(Kin.Dom.1-N-terminal) kinase domain	kd	0.0420	uM
[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethylimidazo[4,5-c]pyridin-7-yl]-piperazin-1-ylmethanone	1798494: In Vitro Kinase Inhibition Assay from Article 10.1021/jm8004527: “Identification of 4-(2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-{[(3S)-3-piperidinylmethyl]oxy}-1H-imidazo[4,5-c]pyridin-4-yl)-2-methyl-3-butyn-2-ol (GSK690693), a novel inhibitor of AKT kinase.”	ic50	0.0470	uM
N-[3-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethylimidazo[4,5-c]pyridin-6-yl]oxyphenyl]-4-(2-morpholin-4-ylethoxy)benzamide	649971: Inhibition of MSK1	ic50	0.0490	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation, affects cotreatment, increases expression	6
sodium arsenite	decreases reaction, increases activity, decreases expression, increases expression, affects cotreatment	4
trichostatin A	affects cotreatment, increases expression	3
N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide	decreases activity	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases methylation	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
decabromobiphenyl ether	increases expression	1
dodecyldimethylamine oxide	increases expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
avermectin	decreases phosphorylation	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
nickel sulfate	increases expression	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	increases expression	1
N-benzyloxycarbonylprolylprolinal	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
fasudil	decreases activity	1
ML 9	decreases activity	1
di-n-butylphosphoric acid	affects expression	1
ML 7	decreases activity	1
SB 203580	decreases reaction, increases activity, affects cotreatment	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases phosphorylation	1
Y 27632	decreases activity	1
U 0126	decreases reaction, increases activity, affects cotreatment	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
obeticholic acid	decreases expression	1
Mangifera indica extract	decreases reaction, increases phosphorylation	1
ormosil	increases expression, affects binding	1

ChEMBL screening assays

659 unique, capped per target: 656 binding, 2 admet, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3734183	Binding	Inhibition of RPS6 kinase phosphorylation in cells (unknown origin) incubated for 6 hrs by Western blot based cell based method	3-(aryl or heteroaryl) methyleneindolin-2-one derivatives as inhibitors of cancer stem cell pathway kinases for the treatment of cancer
CHEMBL4424897	ADMET	Inhibition of human full-length N-terminal His-tagged p70S6K expressed in baculovirus infected Sf21 insect cells using CKRRRLASLR 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
CHEMBL1963744	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: RPS6KA5	PubChem BioAssay data set

Cellosaurus cell lines

7 cell lines: 6 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8UU	Ubigene HCT 116 RPS6KA5 KO	Cancer cell line	Male
CVCL_D9QY	Ubigene HEK293 RPS6KA5 KO	Transformed cell line	Female
CVCL_DX53	HAP1 RPS6KA4 (-) RPS6KA5 (-) 1	Cancer cell line	Male
CVCL_DX54	HAP1 RPS6KA4 (-) RPS6KA5 (-) 2	Cancer cell line	Male
CVCL_DX55	HAP1 RPS6KA4 (-) RPS6KA5 (-) 3	Cancer cell line	Male
CVCL_TJ66	HAP1 RPS6KA5 (-) 1	Cancer cell line	Male
CVCL_TJ67	HAP1 RPS6KA5 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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