RPS6KB1

Summary

RPS6KB1 (ribosomal protein S6 kinase B1, HGNC:10436) is a protein-coding gene on chromosome 17q23.1, encoding Ribosomal protein S6 kinase beta-1 (P23443). Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression.

This gene encodes a member of the ribosomal S6 kinase family of serine/threonine kinases. The encoded protein responds to mTOR (mammalian target of rapamycin) signaling to promote protein synthesis, cell growth, and cell proliferation. Activity of this gene has been associated with human cancer. Alternatively spliced transcript variants have been observed. The use of alternative translation start sites results in isoforms with longer or shorter N-termini which may differ in their subcellular localizations. There are two pseudogenes for this gene on chromosome 17.

Source: NCBI Gene 6198 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypertrophic cardiomyopathy (Moderate, GenCC)
• GWAS associations: 10
• Clinical variants (ClinVar): 40 total
• Druggable target: yes — 39 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_003161

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10436
Approved symbol	RPS6KB1
Name	ribosomal protein S6 kinase B1
Location	17q23.1
Locus type	gene with protein product
Status	Approved
Aliases	S6K1, p70(S6K)-alpha, PS6K, S6K
Ensembl gene	ENSG00000108443
Ensembl biotype	protein_coding
OMIM	608938
Entrez	6198

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 15 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000225577, ENST00000393021, ENST00000406116, ENST00000443572, ENST00000472940, ENST00000475155, ENST00000477179, ENST00000489824, ENST00000587061, ENST00000587622, ENST00000590928, ENST00000592726, ENST00000880474, ENST00000880475, ENST00000880476, ENST00000880477, ENST00000928772, ENST00000928773, ENST00000928774, ENST00000961617, ENST00000961618, ENST00000961619

RefSeq mRNA: 16 — MANE Select: NM_003161 NM_001272042, NM_001272043, NM_001272044, NM_001272060, NM_001369669, NM_001369670, NM_001369671, NM_001369672, NM_001369673, NM_001369674, NM_001369675, NM_001369676, NM_001369677, NM_001369678, NM_001369679, NM_003161

CCDS: CCDS11621, CCDS62271, CCDS62272, CCDS62273

Canonical transcript exons

ENST00000225577 — 15 exons

Exon	Start	End
ENSE00001823154	59893121	59893325
ENSE00001921721	59946551	59950574
ENSE00002366529	59936464	59936541
ENSE00002392810	59936215	59936277
ENSE00003473226	59930117	59930174
ENSE00003480640	59931622	59931722
ENSE00003491425	59912684	59912804
ENSE00003499793	59910562	59910611
ENSE00003504295	59934434	59934524
ENSE00003557960	59940836	59940943
ENSE00003567383	59914635	59914703
ENSE00003570426	59935193	59935300
ENSE00003642206	59926435	59926582
ENSE00003664955	59945406	59945518
ENSE00003680143	59934170	59934260

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 94.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 71.6591 / max 1302.9571, expressed in 1820 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
162031	71.6591	1820

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	94.99	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.07	gold quality
calcaneal tendon	UBERON:0003701	93.40	gold quality
middle temporal gyrus	UBERON:0002771	93.23	gold quality
tibia	UBERON:0000979	93.15	gold quality
colonic epithelium	UBERON:0000397	92.79	gold quality
gingival epithelium	UBERON:0001949	92.73	gold quality
gingiva	UBERON:0001828	92.05	gold quality
adrenal tissue	UBERON:0018303	92.02	gold quality
biceps brachii	UBERON:0001507	91.89	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.75	gold quality
esophagus squamous epithelium	UBERON:0006920	91.67	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	91.13	gold quality
sural nerve	UBERON:0015488	90.63	gold quality
tonsil	UBERON:0002372	90.16	gold quality
cartilage tissue	UBERON:0002418	90.16	gold quality
pigmented layer of retina	UBERON:0001782	89.55	gold quality
retina	UBERON:0000966	89.52	gold quality
upper leg skin	UBERON:0004262	89.48	gold quality
cauda epididymis	UBERON:0004360	89.34	gold quality
corpus epididymis	UBERON:0004359	89.26	gold quality
parietal pleura	UBERON:0002400	89.14	gold quality
body of pancreas	UBERON:0001150	88.88	gold quality
primary visual cortex	UBERON:0002436	88.88	gold quality
caput epididymis	UBERON:0004358	88.87	gold quality
squamous epithelium	UBERON:0006914	88.84	gold quality
visceral pleura	UBERON:0002401	88.83	gold quality
gastrocnemius	UBERON:0001388	88.64	gold quality
muscle of leg	UBERON:0001383	88.51	gold quality
skin of hip	UBERON:0001554	88.44	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.83

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DLX4, ELF1, ESR1, HIF1A, SNAI1, UBTF, YBX1

miRNA regulators (miRDB)

204 targeting RPS6KB1, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-186-5P	99.99	70.83	3707
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-548C-3P	99.99	74.01	7587
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4482-3P	99.98	72.50	3147
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

Literature-anchored findings (GeneRIF, showing 40)

• TF cytoplasmic domain-independent stimulation of protein synthesis via activation of S6 kinase contributes to FVIIa effects in pathophysiology. (PMID:12019261)
• Cdc2 provides a signal that triggers inactivation of S6K1 in mitosis. (PMID:12586835)
• both p70S6K and Akt are activated in the majority of human papillary cancer cells (PMID:12733712)
• Muscarinic receptors mediate activation of this enzymme in astrocytoma cells, coupled with pi 3-kinase activation. (PMID:12747804)
• TNF-receptor activation leads to activation of the p70S6K; TRAF4 is a mediator in this TNF-induced signaling pathway; and TRAF4 inhibits Fas-induced apoptosis (PMID:12801526)
• transient expression of the wild type Rheb1 or Rheb2 causes activation of p70S6K, while expression of Rheb1D60K mutant results in inhibition of basal level activity of p70S6K (PMID:12869548)
• PI3K mediates G(1) progression and cyclin expression through activation of an AKT/mTOR/p70S6K1 signaling pathway in the ovarian cancer cells. (PMID:15028555)
• the increase in basal phosphorylation of p70S6K upon granulocytic differentiation of myeloid leukemic cells and their responses to GM-CSF that are closely paralleled with tyrosyl phosphorylation of its receptor (PMID:15158097)
• Akt and P70S6K phosphorylation and Gadd45 levels are modulated by GPx-1 in tumor cells (PMID:15203190)
• autocrine TGFalpha regulates cell adhesion function by multiple signaling pathways via specific phosphorylation sites of S6K in cancer cells (PMID:15304500)
• the response of muscle protein synthesis to insulin and amino acid is impaired in elderly humans; a defect in S6K1 pathway activation may be responsible for this alteration (PMID:15319361)
• VEGF and HIF-1alpha expression are inhibited by SU5416 through the inhibition of PI3K/AKT/p70S6K1 pathway in ovarian cancer cells (PMID:15474452)
• REVIEW: negative feedback of the PI3K-Akt pathway; one feedback loop composed of mTOR and ribosomal S6 kinase blocks further activation of the pathway through inhibition of insulin receptor substrate function (PMID:15533996)
• Overexpression of ribosomal protein S6 kinase, 70kDa is associated with liver neoplasms (PMID:15623621)
• RSPRR motif interacts with a negative regulator of S6K1 that is normally suppressed by mTOR. (PMID:15659381)
• Ability of hyperinsulinaemia to increase mTOR/p70 S6K pathway activity and IRS-1/2 serine phosphorylation in a tissue-specific fashion. (PMID:15692808)
• identified p70 S6 kinase as a major signal transduction pathway activated by OPN-1 during the migratory response in JAR cells (PMID:15696579)
• S6 kinase 1 is essential for the control of muscle cytoplasmic volume by Akt and mTOR (PMID:15723049)
• interferon alpha has a role in regulating the p70 S6 kinase pathway in chronic myelogenous leukemia cells (PMID:15790787)
• Although zinc could induce cell proliferation and cell growth, and increased phosphorylation of neurofilaments, only cell growth appeared to be related to p7056kinase activation. (PMID:15812314)
• p70S6 kinase is a major effector of mTOR phosphorylation at Ser-2448 in response to both mitogen- and nutrient-derived stimuli (PMID:15899889)
• The mainly anti-apoptotic p70S6k signalling is downregulated in cellular and transgenic models of Alzheimer’s disease and in peripheral cells of patients, and could contribute to the pathogenesis of the disease. (PMID:15953364)
• hVps34 is a nutrient-regulated lipid kinase that integrates amino acid and glucose inputs to mTOR and S6K1 (PMID:16049009)
• These data suggest that PI3K-dependent T389/T229 phosphorylation is limiting in late-phase p70S6K activation by EGF and contributes to the cooperative effect of GPCRs on p70S6K activity and cell growth. (PMID:16262259)
• S6K1 maneuvers on and off the eukaryotic initiation factor 3 translation initiation complex. (PMID:16286006)
• mTOR nuclear import is required for its cytoplasmic signaling to S6K1 (PMID:16407298)
• We conclude that resistance exercise effectively increases the phosphorylation of S6K1 on Thr421/Ser424, which is not associated with a substantial increase in S6 phosphorylation in a fasted state. (PMID:16434552)
• p70S6K activation induces expression of MMP-9 associated with hepatocyte growth factor-mediated invasion in human ovarian cancer cells (PMID:16469801)
• both S6K1 and eukaryotic translation initiation factor 4E binding protein 1 pathways, regulated by TORC1, are required for cell motility (PMID:16715128)
• The higher expressions of p-p70S6K was associated with worse outcome in glioblastoma. (PMID:16818690)
• In the presence of urokinase plasminogen activator, overexpression of ganglioside GM3 paradoxically increases proliferation of carcinoma cells by augmenting ERK-independent p70S6 kinase activation. (PMID:16826166)
• Inhibition of p70S6K1 activity by its siRNA also decreased cell migration, invasion, and proliferation associated with the induction of p27(KIP1) levels, and with the inhibition of cell cycle-associated proteins. (PMID:16839745)
• These results suggest that p70S6K1 regulates turnover of HDM2 protein for cancer development. (PMID:16883576)
• These studies suggest that, through serine phosphorylation, Raptor-mTOR and S6K1 promote the depletion of IRS1 from specific intracellular pools in pathological states of insulin and IGF-I resistance and in lesions associated with tuberous sclerosis. (PMID:16914728)
• Collectively, these data suggested that acetaldehyde did not adversely affect glucose uptake despite inhibition of insulin signaling cascade at the levels of Akt and mTOR, possibly due to enhanced p70(S6K) phosphorylation. (PMID:16962100)
• This study demonstrates a novel mechanism of EGF-induced VEGF and HIF-1alpha expression through production of H2O2 and activation of AKT and p70S6K1 in human ovarian cancer cells. (PMID:17045920)
• S6K1 regulates GSK3 under conditions of mTOR-dependent feedback inhibition of Akt (PMID:17052453)
• in response to mitogens, PDCD4 was rapidly phosphorylated by protein kinase S6K1 & then degraded by ubiquitin ligase SCF(betaTRCP); it is proposed that regulated degradation of PDCD4 in response to mitogens allows efficient protein synthesis & cell growth (PMID:17053147)
• p70 S6 kinase activates PAK1 and contributes to phosphatidylinositol 3-kinase- and ERK-mediated regulation of HCV RNA replication (PMID:17255101)
• Monitoring P70(S6K) phosphorylation can help predict and monitor the biological effectiveness of rapamycin in renal transplant recipients with Kaposi sarcoma. (PMID:17336708)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rps6kb1	ENSMUSG00000020516
rattus_norvegicus	Rps6kb1	ENSRNOG00000003919
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), RPS6KA5 (ENSG00000100784), RPS6KA1 (ENSG00000117676), RPS6KA4 (ENSG00000162302), RPS6KB2 (ENSG00000175634), RPS6KA3 (ENSG00000177189)

Protein

Protein identifiers

Ribosomal protein S6 kinase beta-1 — P23443 (reviewed: P23443)

Alternative names: 70 kDa ribosomal protein S6 kinase 1, Ribosomal protein S6 kinase I, Serine/threonine-protein kinase 14A, p70 ribosomal S6 kinase alpha

All UniProt accessions (4): P23443, K7EIM2, K7EMM2, K7ER06

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression. Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD. Under conditions of nutrient depletion, the inactive form associates with the EIF3 translation initiation complex. Upon mitogenic stimulation, phosphorylation by the mechanistic target of rapamycin complex 1 (mTORC1) leads to dissociation from the EIF3 complex and activation. The active form then phosphorylates and activates several substrates in the pre-initiation complex, including the EIF2B complex and the cap-binding complex component EIF4B. Also controls translation initiation by phosphorylating a negative regulator of EIF4A, PDCD4, targeting it for ubiquitination and subsequent proteolysis. Promotes initiation of the pioneer round of protein synthesis by phosphorylating POLDIP3/SKAR. In response to IGF1, activates translation elongation by phosphorylating EEF2 kinase (EEF2K), which leads to its inhibition and thus activation of EEF2. Also plays a role in feedback regulation of mTORC2 by mTORC1 by phosphorylating MAPKAP1/SIN1, MTOR and RICTOR, resulting in the inhibition of mTORC2 and AKT1 signaling. Also involved in feedback regulation of mTORC1 and mTORC2 by phosphorylating DEPTOR. Mediates cell survival by phosphorylating the pro-apoptotic protein BAD and suppressing its pro-apoptotic function. Phosphorylates mitochondrial URI1 leading to dissociation of a URI1-PPP1CC complex. The free mitochondrial PPP1CC can then dephosphorylate RPS6KB1 at Thr-412, which is proposed to be a negative feedback mechanism for the RPS6KB1 anti-apoptotic function. Mediates TNF-induced insulin resistance by phosphorylating IRS1 at multiple serine residues, resulting in accelerated degradation of IRS1. In cells lacking functional TSC1-2 complex, constitutively phosphorylates and inhibits GSK3B. May be involved in cytoskeletal rearrangement through binding to neurabin. Phosphorylates and activates the pyrimidine biosynthesis enzyme CAD, downstream of MTOR. Following activation by mTORC1, phosphorylates EPRS and thereby plays a key role in fatty acid uptake by adipocytes and also most probably in interferon-gamma-induced translation inhibition.

Subunit / interactions. Interacts with PPP1R9A/neurabin-1. Interacts with RPTOR. Interacts with IRS1. Interacts with EIF3B and EIF3C. Interacts with TRAF4. Interacts with POLDIP3. Interacts (via N-terminus) with IER5. (Microbial infection) Interacts with Mumps virus phosphoprotein; this interaction may play a role in the viral replication and transcription.

Subcellular location. Synapse. Synaptosome. Mitochondrion outer membrane. Mitochondrion Nucleus. Cytoplasm Cytoplasm.

Tissue specificity. Widely expressed.

Post-translational modifications. Phosphorylation at Thr-412 is regulated by mTORC1. The phosphorylation at this site is maintained by an agonist-dependent autophosphorylation mechanism. Activated by phosphorylation at Thr-252 by PDPK1. Dephosphorylation by PPP1CC at Thr-412 in mitochondrion.

Activity regulation. Activation requires multiple phosphorylation events on serine/threonine residues. Activation appears to be first mediated by phosphorylation of multiple sites in the autoinhibitory domain, which facilitates phosphorylation at Thr-412, disrupting the autoinhibitory mechanism and allowing phosphorylation of Thr-252 by PDPK1. The active conformation of the kinase is believed to be stabilized by a mechanism involving three conserved phosphorylation sites located in the kinase domain activation loop (Thr-252) and in the AGC-kinase C-terminal domain (Ser-394 in the middle of the tail/linker region and Thr-412 within a hydrophobic motif at its end). Activated by mTORC1; isoform Alpha I and isoform Alpha II are sensitive to rapamycin, which inhibits activating phosphorylation at Thr-412. Activated by PDPK1.

Domain organisation. The autoinhibitory domain is believed to block phosphorylation within the AGC-kinase C-terminal domain and the activation loop. The TOS (TOR signaling) motif is essential for activation by mTORC1.

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

Isoforms (5)

UniProt ID	Names	Canonical?
P23443-1	Alpha I, p80-S6K 1	yes
P23443-2	Alpha II
P23443-3	2
P23443-5	4
P23443-4	3

RefSeq proteins (16): NP_001258971, NP_001258972, NP_001258973, NP_001258989, NP_001356598, NP_001356599, NP_001356600, NP_001356601, NP_001356602, NP_001356603, NP_001356604, NP_001356605, NP_001356606, NP_001356607, NP_001356608, NP_003152* (*=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
IPR016238	Ribosomal_S6_kinase	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR017892	Pkinase_C	Domain

Pfam: PF00069, PF00433

Enzyme classification (BRENDA):

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

Substrate kinetics (BRENDA)

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

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

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (75 total): helix 19, strand 12, modified residue 9, mutagenesis site 7, sequence variant 5, turn 5, splice variant 4, region of interest 3, domain 2, binding site 2, sequence conflict 2, compositionally biased region 2, chain 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

22 structures.

PDB	Method	Resolution (Å)
5WBH	X-RAY DIFFRACTION	1.75
3WF7	X-RAY DIFFRACTION	1.85
3WF8	X-RAY DIFFRACTION	1.98
3WE4	X-RAY DIFFRACTION	2
3WF6	X-RAY DIFFRACTION	2.03
3WF9	X-RAY DIFFRACTION	2.04
3WF5	X-RAY DIFFRACTION	2.1
4L3J	X-RAY DIFFRACTION	2.1
4L3L	X-RAY DIFFRACTION	2.1
3A62	X-RAY DIFFRACTION	2.35
4RLO	X-RAY DIFFRACTION	2.53
7N93	X-RAY DIFFRACTION	2.74
4RLP	X-RAY DIFFRACTION	2.79
3A60	X-RAY DIFFRACTION	2.8
4L42	X-RAY DIFFRACTION	2.8
4L44	X-RAY DIFFRACTION	2.9
4L45	X-RAY DIFFRACTION	2.9
4L43	X-RAY DIFFRACTION	3
7N91	X-RAY DIFFRACTION	3
4L46	X-RAY DIFFRACTION	3.01
5WBK	X-RAY DIFFRACTION	3.11
3A61	X-RAY DIFFRACTION	3.43

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P23443-F1	72.54	0.48

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): 218 (proton acceptor)

Ligand- & substrate-binding residues (2): 97–105; 123

Post-translational modifications (9): 252, 394, 412, 434, 441, 444, 447, 452, 516

Mutagenesis-validated functional residues (7):

Position	Phenotype
167	greatly reduces activity. greatly reduces phosphorylation at t-412 and moderately reduces phosphorylation at t-252.
394	loss of activity. loss of phosphorylation at t-412.
412	mimics phosphorylation. facilitates phosphorylation of t-252 by pdpk1; when associated with e-434; e-441; e-444 and e-44
434	facilitates phosphorylation of t-252 by pdpk1; when associated with e-412; e-441; e-444 and e-447.
441	facilitates phosphorylation of t-252 by pdpk1; when associated with e-412; e-434; e-444 and e-447.
444	facilitates phosphorylation of t-252 by pdpk1; when associated with e-412; e-434; e-441 and e-447.
447	facilitates phosphorylation of t-252 by pdpk1; when associated with e-412; e-434; e-441 and e-444.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-166208	mTORC1-mediated signalling
R-HSA-162582	Signal Transduction
R-HSA-165159	MTOR signalling

MSigDB gene sets: 513 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_BEHAVIOR, TGCGCANK_UNKNOWN, PID_TELOMERASE_PATHWAY, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_RESPONSE_TO_CORTICOSTEROID, TTTGTAG_MIR520D, AREB6_03, GOBP_PEPTIDYL_SERINE_MODIFICATION, AAGCCAT_MIR135A_MIR135B, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, GOBP_CELL_CYCLE_PHASE_TRANSITION

GO Biological Process (39): G1/S transition of mitotic cell cycle (GO:0000082), behavioral fear response (GO:0001662), apoptotic process (GO:0006915), signal transduction (GO:0007165), germ cell development (GO:0007281), peptidyl-serine phosphorylation (GO:0018105), response to nutrient levels (GO:0031667), cellular response to nutrient (GO:0031670), TOR signaling (GO:0031929), cellular response to insulin stimulus (GO:0032869), TORC1 signaling (GO:0038202), negative regulation of apoptotic process (GO:0043066), long-chain fatty acid import into cell (GO:0044539), positive regulation of translation (GO:0045727), positive regulation of mitotic cell cycle (GO:0045931), positive regulation of translational initiation (GO:0045948), negative regulation of insulin receptor signaling pathway (GO:0046627), phosphatidylinositol-mediated signaling (GO:0048015), modulation of chemical synaptic transmission (GO:0050804), cellular response to type II interferon (GO:0071346), cellular response to growth factor stimulus (GO:0071363), cellular response to dexamethasone stimulus (GO:0071549), negative regulation of TORC2 signaling (GO:1903940), positive regulation of TORC1 signaling (GO:1904263), negative regulation of extrinsic apoptotic signaling pathway (GO:2001237), autophagosome assembly (GO:0000045), cytoplasmic translation (GO:0002181), regulation of translation (GO:0006417), protein phosphorylation (GO:0006468), ubiquitin-dependent protein catabolic process (GO:0006511), insulin receptor signaling pathway (GO:0008286), negative regulation of autophagy (GO:0010507), positive regulation of autophagy (GO:0010508), SCF-dependent proteasomal ubiquitin-dependent protein catabolic process (GO:0031146), cellular response to nutrient levels (GO:0031669), TORC2 signaling (GO:0038203), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), negative regulation of TORC1 signaling (GO:1904262)

GO Molecular Function (9): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), protein serine/threonine/tyrosine kinase activity (GO:0004712), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (10): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), cytosol (GO:0005829), neuron projection (GO:0043005), glutamatergic synapse (GO:0098978), membrane (GO:0016020), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
MTOR signalling	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein kinase activity	3
mitotic cell cycle	2
intracellular signal transduction	2
intracellular membrane-bounded organelle	2
cytoplasm	2
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
behavioral defense response	1
fear response	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
developmental process involved in reproduction	1
gamete generation	1
cellular process involved in reproduction in multicellular organism	1
cell development	1
protein phosphorylation	1
peptidyl-serine modification	1
response to stimulus	1
response to nutrient	1
cellular response to nutrient levels	1
cellular response to chemical stimulus	1
response to insulin	1
cellular response to peptide hormone stimulus	1
TOR signaling	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
long-chain fatty acid transport	1
import into cell	1
lipid import into cell	1
translation	1
regulation of translation	1
positive regulation of gene expression	1

Protein interactions and networks

STRING

5172 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPS6KB1	RPTOR	Q8N122	999
RPS6KB1	EIF4E	P06730	980
RPS6KB1	MTOR	P42345	978
RPS6KB1	EIF4EBP1	Q13541	972
RPS6KB1	RPS6	P08227	971
RPS6KB1	TSC2	P49815	943
RPS6KB1	RHEB	Q15382	923
RPS6KB1	EIF4B	P23588	915
RPS6KB1	MLST8	Q9BVC4	909
RPS6KB1	PTEN	P60484	904
RPS6KB1	RICTOR	Q6R327	903
RPS6KB1	AKT1S1	Q96B36	899
RPS6KB1	DEPTOR	Q8TB45	894
RPS6KB1	TSC1	Q92574	893
RPS6KB1	POLDIP3	Q9BY77	892

IntAct

79 interactions, top by confidence:

A	B	Type	Score
EIF3B	EIF4E	psi-mi:“MI:0914”(association)	0.640
AKT1	RPS6KB1	psi-mi:“MI:0914”(association)	0.640
AKT1	RPS6KB1	psi-mi:“MI:2364”(proximity)	0.640
AKT1	RPS6KB1	psi-mi:“MI:0915”(physical association)	0.640
RPS6KB1	RPTOR	psi-mi:“MI:0915”(physical association)	0.610
RPS6KB1	RPTOR	psi-mi:“MI:0407”(direct interaction)	0.610
EIF3B	RPS6KB1	psi-mi:“MI:0915”(physical association)	0.560
MTOR	RPS6KB1	psi-mi:“MI:0407”(direct interaction)	0.560
APLP2	RPS6KB1	psi-mi:“MI:0915”(physical association)	0.560
UNG	RPS6KB1	psi-mi:“MI:0915”(physical association)	0.560
RPS6KB1	MTOR	psi-mi:“MI:0217”(phosphorylation reaction)	0.560
RPS6KB1	COASY	psi-mi:“MI:0915”(physical association)	0.540
COASY	RPS6KB1	psi-mi:“MI:0915”(physical association)	0.540
COASY	RPS6KB1	psi-mi:“MI:0407”(direct interaction)	0.540
PPP2R2B	RPS6KB1	psi-mi:“MI:0914”(association)	0.500
PPP2R2B	RPS6KB1	psi-mi:“MI:0915”(physical association)	0.500
RPS6KB1	MXD1	psi-mi:“MI:0407”(direct interaction)	0.440
RAPTOR1	RPS6KB1	psi-mi:“MI:0407”(direct interaction)	0.440
AKT1S1	RPS6KB1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
PDK1	RPS6KB1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
RPS6KB1	MAPT	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
MAPT	RPS6KB1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440

BioGRID (223): RPS6KB1 (Affinity Capture-Western), RPS6KB1 (Affinity Capture-Western), RPS6KB1 (Affinity Capture-Western), RHEB (Biochemical Activity), MTOR (Affinity Capture-Western), NR1I2 (Biochemical Activity), RPS6KB1 (Biochemical Activity), IRS1 (Reconstituted Complex), RPS6KB1 (Affinity Capture-Western), EIF3B (Biochemical Activity), EIF3F (Biochemical Activity), RPS6KB1 (Biochemical Activity), RPS6KB1 (Affinity Capture-MS), RPS6KB1 (Co-localization), RPS6KB1 (Co-localization)

ESM2 similar proteins: A1Z9X0, A8WUG4, A8XWC4, F1M7Y5, O13310, O19111, O74536, O97627, P00518, P07934, P09217, P13286, P23443, P26817, P26818, P26819, P31325, P34722, P35626, P41743, P54645, P54646, P67998, P67999, P83099, Q02111, Q02956, Q04759, Q05513, Q09137, Q12706, Q13131, Q16816, Q19266, Q21734, Q28948, Q2KJ16, Q3UYH7, Q5EG47, Q5R4K9

Diamond homologs: A1Z9X0, A7MB74, A8KBH6, A8XNJ6, F1M7Y5, J9W0G9, O00141, O19111, P04409, P05126, P05128, P05129, P05130, P05696, P05771, P05772, P09216, P09217, P10102, P10829, P10830, P11792, P12688, P13678, P16054, P17252, P18961, P20444, P23298, P23443, P24723, P28178, P31748, P31749, P31750, P31751, P34885, P36582, P36583, P41743

SIGNOR signaling

104 interactions.

A	Effect	B	Mechanism
RPS6KB1	“down-regulates activity”	MTOR	phosphorylation
RPS6KB1	“down-regulates activity”	EEF2K	phosphorylation
CDK1	up-regulates	RPS6KB1	phosphorylation
MAPK1	up-regulates	RPS6KB1	phosphorylation
MAPK3	“up-regulates activity”	RPS6KB1	phosphorylation
RPS6KB1	up-regulates	EIF4B	phosphorylation
RPS6KB1	unknown	POLDIP3	phosphorylation
RPS6KB1	“down-regulates activity”	IRS1	phosphorylation
RPS6KB1	down-regulates	MAPK8
RPS6KB1	down-regulates	PDCD4	phosphorylation
RPS6KB1	down-regulates	RICTOR	phosphorylation
PPP2R5C	down-regulates	RPS6KB1	binding
RPS6KB1	down-regulates	DEPTOR	phosphorylation
RPS6KB1	down-regulates	MXD1	phosphorylation
RPS6KB1	down-regulates	TP63	phosphorylation
RPS6KB1	unknown	CCT2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 46 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
VEGFR2 mediated vascular permeability	7	75.1×	2e-09
Constitutive Signaling by AKT1 E17K in Cancer	6	66.8×	5e-08
CD28 dependent PI3K/Akt signaling	5	51.8×	4e-06
Co-stimulation by CD28	5	50.1×	4e-06
Regulation of TP53 Degradation	6	46.2×	4e-07
MTOR signalling	5	34.9×	2e-05
High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells	5	21.2×	2e-04
VEGFA-VEGFR2 Pathway	5	18.3×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
T cell costimulation	5	44.6×	1e-05
positive regulation of stress fiber assembly	5	37.1×	2e-05
epidermal growth factor receptor signaling pathway	6	35.4×	4e-06
positive regulation of cell growth	7	30.5×	2e-06
cellular response to insulin stimulus	5	20.3×	3e-04
regulation of actin cytoskeleton organization	5	18.8×	4e-04
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	8	14.9×	1e-05
protein phosphorylation	7	11.3×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

3634 predictions. Top by Δscore:

Variant	Effect	Δscore
17:59893242:G:T	donor_gain	1.0000
17:59893293:G:GT	donor_gain	1.0000
17:59893308:GA:G	donor_gain	1.0000
17:59893322:GGGG:G	donor_gain	1.0000
17:59893323:G:GT	donor_gain	1.0000
17:59893923:GG:G	donor_gain	1.0000
17:59893924:GG:G	donor_gain	1.0000
17:59910607:GAACT:G	donor_gain	1.0000
17:59910612:G:GG	donor_gain	1.0000
17:59912682:A:AG	acceptor_gain	1.0000
17:59912682:AGT:A	acceptor_gain	1.0000
17:59912683:G:GA	acceptor_gain	1.0000
17:59912683:GT:G	acceptor_gain	1.0000
17:59912683:GTG:G	acceptor_gain	1.0000
17:59912683:GTGGC:G	acceptor_gain	1.0000
17:59914630:TCCA:T	acceptor_loss	1.0000
17:59914632:CAGG:C	acceptor_loss	1.0000
17:59914634:G:GA	acceptor_loss	1.0000
17:59926568:T:G	donor_gain	1.0000
17:59926568:T:TG	donor_gain	1.0000
17:59926580:GTG:G	donor_gain	1.0000
17:59930114:CAGGA:C	acceptor_loss	1.0000
17:59930115:A:AG	acceptor_gain	1.0000
17:59930115:AG:A	acceptor_gain	1.0000
17:59930115:AGGAG:A	acceptor_gain	1.0000
17:59930116:G:GA	acceptor_gain	1.0000
17:59930116:GG:G	acceptor_gain	1.0000
17:59930116:GGA:G	acceptor_gain	1.0000
17:59930116:GGAGG:G	acceptor_gain	1.0000
17:59930175:G:GG	donor_gain	1.0000

AlphaMissense

3467 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:59912764:T:C	F91S	1.000
17:59912782:T:A	L97H	1.000
17:59912784:G:C	G98R	1.000
17:59912785:G:A	G98D	1.000
17:59912785:G:T	G98V	1.000
17:59912790:G:A	G100R	1.000
17:59912790:G:C	G100R	1.000
17:59912790:G:T	G100W	1.000
17:59912791:G:A	G100E	1.000
17:59912799:G:A	G103R	1.000
17:59912799:G:C	G103R	1.000
17:59912800:G:A	G103E	1.000
17:59912800:G:T	G103V	1.000
17:59914684:C:A	A121D	1.000
17:59914689:A:C	K123Q	1.000
17:59914689:A:G	K123E	1.000
17:59914691:G:C	K123N	1.000
17:59914691:G:T	K123N	1.000
17:59914696:T:A	L125H	1.000
17:59914696:T:C	L125P	1.000
17:59914703:G:C	K127N	1.000
17:59914703:G:T	K127N	1.000
17:59926442:T:A	I130K	1.000
17:59926468:C:G	H139D	1.000
17:59926477:G:C	A142P	1.000
17:59926480:G:A	E143K	1.000
17:59926482:A:C	E143D	1.000
17:59926482:A:T	E143D	1.000
17:59926484:G:C	R144P	1.000
17:59926493:T:C	L147P	1.000

dbSNP variants (sampled 300 via entrez): RS1000021445 (17:59891985 A>T), RS1000078566 (17:59899158 C>T), RS1000088639 (17:59899538 A>G), RS1000165924 (17:59930330 G>A), RS1000202174 (17:59919362 G>A), RS1000250066 (17:59944943 C>G,T), RS1000335954 (17:59937979 C>G,T), RS1000336935 (17:59893558 G>A), RS1000433453 (17:59905623 G>A), RS1000477988 (17:59891551 T>C), RS1000486347 (17:59912240 A>G), RS1000603006 (17:59925364 T>C), RS1000657588 (17:59919105 C>G,T), RS1000728850 (17:59923912 A>G), RS1000852170 (17:59900225 C>A,G,T)

Disease associations

OMIM: gene MIM:608938 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
hypertrophic cardiomyopathy	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
hypertrophic cardiomyopathy	Limited	AD

Mondo (1): hypertrophic cardiomyopathy (MONDO:0005045)

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001198_74	Multiple sclerosis	9.000000e-08
GCST001725_56	Inflammatory bowel disease	9.000000e-13
GCST001762_939	Obesity-related traits	3.000000e-06
GCST004132_90	Crohn’s disease	1.000000e-06
GCST005537_35	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	3.000000e-11
GCST006613_35	Triglycerides	1.000000e-09
GCST007615_42	C-reactive protein levels	1.000000e-09
GCST007615_77	C-reactive protein levels	7.000000e-08
GCST008721_6	Chronic lymphocytic leukemia or multiple sclerosis	3.000000e-08
GCST012231_139	A body shape index	9.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005116	urinary metabolite measurement
EFO:0004530	triglyceride measurement
EFO:0004458	C-reactive protein measurement
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2111330 (PROTEIN COMPLEX), CHEMBL3832633 (PROTEIN FAMILY), CHEMBL3885629 (PROTEIN FAMILY), CHEMBL4501 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

39 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 320,932 (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
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL101253	VATALANIB	3	11,319
CHEMBL223360	LINIFANIB	3	3,925
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
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1721885	SU-014813	2	363
CHEMBL1967878	CENISERTIB	2	358
CHEMBL1980297	ILORASERTIB	2	581
CHEMBL1980715	LAUROGUADINE	2
CHEMBL215152	DEFOSBARASERTIB	2
CHEMBL3137336	UPROSERTIB	2
CHEMBL3544911	PREXASERTIB	2
CHEMBL475251	R-406	2
CHEMBL4871106	RUPITASERTIB	2
CHEMBL495727	AT-9283	2
CHEMBL565612	SOTRASTAURIN	2
CHEMBL572878	TOZASERTIB	2
CHEMBL3544960	AT-13148	1

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — p70 subfamily

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

Ligand	Action	Affinity	Parameter
rupitasertib	Inhibition	9.0	pIC50
LY2584702	Inhibition	8.4	pIC50
compound 1 [PMID: 20005102]	Inhibition	8.15	pIC50
compound E22 [PMID: 31298542]	Inhibition	8.05	pIC50
PF-4708671	Inhibition	7.7	pIC50
Sanofi-14h	Inhibition	7.12	pIC50
GNE-3511	Inhibition	5.71	pIC50

Binding affinities (BindingDB)

1410 measured of 1559 human assays (1559 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-[[(1R)-1-[3-[(5-propan-2-yl-1H-pyrazole-3-carbonyl)amino]phenyl]ethyl]amino]quinazoline-8-carboxamide	IC50	0.03 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[(1R)-1-[3-[(5-tert-butyl-1H-pyrazole-3-carbonyl)amino]phenyl]ethyl]amino]quinazoline-8-carboxamide	IC50	0.03 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[1-[3-[(4-bromobenzoyl)amino]phenyl]-3-methoxypropyl]amino]quinazoline-8-carboxamide	IC50	0.05 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[3-methoxy-1-[3-[[4-(trifluoromethoxy)benzoyl]amino]phenyl]propyl]amino]quinazoline-8-carboxamide	IC50	0.05 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[1-[3-[(5-propan-2-yl-1H-pyrazole-3-carbonyl)amino]phenyl]ethylamino]quinazoline-8-carboxamide	IC50	0.06 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[3-[(4-methoxybenzoyl)amino]phenyl]methylamino]-6-(2-methoxyethoxy)quinazoline-8-carboxamide	IC50	0.06 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[(1R)-1-[3-[(6-methoxypyridine-3-carbonyl)amino]phenyl]ethyl]amino]quinazoline-8-carboxamide	IC50	0.07 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[(1R)-1-[3-[[6-(trifluoromethyl)pyridine-3-carbonyl]amino]phenyl]ethyl]amino]quinazoline-8-carboxamide	IC50	0.07 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[1-[3-[(5-tert-butyl-1H-pyrazole-3-carbonyl)amino]phenyl]ethylamino]quinazoline-8-carboxamide	IC50	0.08 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[(1R)-1-[3-[(4-cyano-2-pyridinyl)amino]phenyl]ethyl]amino]quinazoline-8-carboxamide	IC50	0.08 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[1-[3-[(5-fluoro-4-methylcyclohexa-1,5-diene-1-carbonyl)amino]phenyl]ethylamino]quinazoline-8-carboxamide	IC50	0.09 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[3-hydroxy-1-[3-[(4-methoxybenzoyl)amino]phenyl]propyl]amino]quinazoline-8-carboxamide	IC50	0.09 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[3-[[6-[2-methoxyethyl(methyl)amino]pyridine-3-carbonyl]amino]phenyl]methylamino]quinazoline-8-carboxamide	IC50	0.09 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[1-[3-[(6-methoxypyridine-3-carbonyl)amino]phenyl]ethylamino]quinazoline-8-carboxamide	IC50	0.1 nM	US-8637532: Amino azaheterocyclic carboxamides
6-[4-[1-[2-(azetidin-1-yl)ethyl]-4-(4-fluoro-3-methylphenyl)imidazol-2-yl]piperidin-1-yl]-5-bromopyrimidin-4-amine	IC50	0.1 nM	US-9145392: Imidazole amines as modulators of kinase activity
4-[[3-[[4-(dimethylamino)benzoyl]amino]phenyl]methylamino]quinazoline-8-carboxamide	IC50	0.11 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[(1R)-1-[3-[[2-fluoro-5-(trifluoromethyl)benzoyl]amino]phenyl]ethyl]amino]quinazoline-8-carboxamide	IC50	0.11 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[3-[(2,4-dichlorobenzoyl)amino]phenyl]methylamino]quinazoline-8-carboxamide	IC50	0.12 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[1-[3-[(4-bromobenzoyl)amino]phenyl]-3-(dimethylamino)propyl]amino]quinazoline-8-carboxamide	IC50	0.12 nM	US-8637532: Amino azaheterocyclic carboxamides
1-[[(1R)-1-[4-fluoro-3-[(3-fluoro-4-methoxybenzoyl)amino]phenyl]ethyl]amino]isoquinoline-5-carboxamide	IC50	0.12 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[(1R)-1-[3-(cyclopentanecarbonylamino)phenyl]ethyl]amino]quinazoline-8-carboxamide	IC50	0.12 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[(1R)-1-[3-[(3-fluoro-4-methoxybenzoyl)amino]phenyl]ethyl]amino]quinazoline-8-carboxamide	IC50	0.13 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[3-[[2-(methylamino)pyridine-4-carbonyl]amino]phenyl]methylamino]quinazoline-8-carboxamide	IC50	0.15 nM	US-8637532: Amino azaheterocyclic carboxamides
6-[4-[1-[2-(azetidin-1-yl)ethyl]-4-(2-propan-2-yl-4-pyridinyl)imidazol-2-yl]piperidin-1-yl]-5-bromopyrimidin-4-amine	IC50	0.15 nM	US-9145392: Imidazole amines as modulators of kinase activity
4-[[3-[(2,4-difluorobenzoyl)amino]phenyl]methylamino]quinazoline-8-carboxamide	IC50	0.16 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[1-[3-[(4-methoxybenzoyl)amino]phenyl]-3-[methyl(prop-2-enyl)amino]propyl]amino]quinazoline-8-carboxamide	IC50	0.16 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[1-[3-[(4-bromobenzoyl)amino]phenyl]-2-(methylamino)ethyl]amino]quinazoline-8-carboxamide	IC50	0.17 nM	US-8637532: Amino azaheterocyclic carboxamides
10-[[2-(methylamino)-1-[3-[[4-(trifluoromethoxy)benzoyl]amino]phenyl]ethyl]amino]-1,3-diazecine-5-carboxamide	IC50	0.17 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[3-[[[2-fluoro-5-(trifluoromethyl)phenyl]-hydroxymethyl]amino]phenyl]methylamino]quinazoline-8-carboxamide	IC50	0.17 nM	US-8637532: Amino azaheterocyclic carboxamides
6-(3-piperidin-1-ylpropoxy)-4-[[4-(trifluoromethyl)phenyl]methylamino]quinazoline-8-carboxamide	IC50	0.18 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[3-methoxy-1-[3-[[4-(trifluoromethyl)benzoyl]amino]phenyl]propyl]amino]quinazoline-8-carboxamide	IC50	0.18 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[1-[3-[(2-fluoro-4-methoxybenzoyl)amino]phenyl]-3-methoxypropyl]amino]quinazoline-8-carboxamide	IC50	0.18 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[1-[3-[(2,2-difluorocyclopropanecarbonyl)amino]phenyl]ethylamino]quinazoline-8-carboxamide	IC50	0.18 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[1-(3-benzamidophenyl)-3-(dimethylamino)propyl]amino]quinazoline-8-carboxamide	IC50	0.18 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[(1R)-1-[3-[[3-fluoro-4-(trifluoromethoxy)benzoyl]amino]phenyl]ethyl]amino]quinazoline-8-carboxamide	IC50	0.18 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[1-[3-[(4-chloro-3-fluorobenzoyl)amino]phenyl]ethylamino]quinazoline-8-carboxamide	IC50	0.2 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[1-[3-[[5-(difluoromethyl)-1H-pyrazole-3-carbonyl]amino]phenyl]ethylamino]quinazoline-8-carboxamide	IC50	0.2 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[1-[3-[(3,4-difluorobenzoyl)amino]phenyl]-3-methoxypropyl]amino]quinazoline-8-carboxamide	IC50	0.2 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[(5Z)-5-[hydroxy-(4-methoxy-3-methylphenyl)methyl]iminocyclohex-3-en-1-yl]methylamino]quinazoline-8-carboxamide	IC50	0.2 nM	US-8637532: Amino azaheterocyclic carboxamides
6-(4-hydroxybutyl)-4-[[3-[(4-methoxybenzoyl)amino]phenyl]methylamino]quinazoline-8-carboxamide	IC50	0.2 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[(1S)-1-(3-chlorophenyl)-2-(methylamino)ethyl]amino]-6-methoxyquinazoline-8-carboxamide	IC50	0.2 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[1-[3-[(4-bromo-3-fluorobenzoyl)amino]phenyl]ethylamino]quinazoline-8-carboxamide	IC50	0.21 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[1-[3-[[6-(trifluoromethyl)pyridine-3-carbonyl]amino]phenyl]ethylamino]quinazoline-8-carboxamide	IC50	0.21 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[(1R)-3-methoxy-1-[3-[(4-methoxybenzoyl)amino]phenyl]propyl]amino]quinazoline-8-carboxamide	IC50	0.21 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[(1R)-1-[3-[(2-methoxypyridine-4-carbonyl)amino]phenyl]ethyl]amino]quinazoline-8-carboxamide	IC50	0.22 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[3-[[5-(trifluoromethyl)-1H-pyrazole-3-carbonyl]amino]phenyl]methylamino]quinazoline-8-carboxamide	IC50	0.22 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[3-[[2-(2-methylpropylamino)pyridine-4-carbonyl]amino]phenyl]methylamino]quinazoline-8-carboxamide	IC50	0.22 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[3-[[5-(aminomethyl)-1,3-thiazol-2-yl]amino]phenyl]methylamino]quinazoline-8-carboxamide	IC50	0.22 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[4-fluoro-3-[[4-(trifluoromethoxy)benzoyl]amino]phenyl]methylamino]quinazoline-8-carboxamide	IC50	0.22 nM	US-8637532: Amino azaheterocyclic carboxamides
4-[[3-(2,3-dihydro-1-benzofuran-5-carbonylamino)phenyl]methylamino]quinazoline-8-carboxamide	IC50	0.23 nM	US-8637532: Amino azaheterocyclic carboxamides

ChEMBL bioactivities

2196 potent at pChembl≥5 of 2253 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.22	IC50	0.06	nM	CHEMBL3936990
10.00	IC50	0.1	nM	CHEMBL3899716
9.96	IC50	0.11	nM	CHEMBL3966806
9.92	IC50	0.12	nM	CHEMBL3675393
9.85	IC50	0.14	nM	CHEMBL3675394
9.70	IC50	0.2	nM	CHEMBL3685328
9.70	IC50	0.2	nM	CHEMBL3906990
9.70	IC50	0.2	nM	CHEMBL3980521
9.59	IC50	0.26	nM	CHEMBL3981085
9.55	IC50	0.28	nM	CHEMBL3675395
9.44	IC50	0.36	nM	CHEMBL3675396
9.41	IC50	0.39	nM	CHEMBL3675397
9.40	IC50	0.4	nM	CHEMBL3894849
9.38	IC50	0.42	nM	CHEMBL3675398
9.38	IC50	0.42	nM	CHEMBL3675399
9.37	IC50	0.43	nM	STAUROSPORINE
9.36	IC50	0.44	nM	CHEMBL3943127
9.30	IC50	0.5	nM	CHEMBL3670401
9.30	IC50	0.5	nM	CHEMBL3675326
9.30	IC50	0.5	nM	CHEMBL3675331
9.30	IC50	0.5	nM	CHEMBL3977147
9.30	IC50	0.5	nM	CHEMBL3978595
9.30	IC50	0.5	nM	CHEMBL3971598
9.28	IC50	0.53	nM	CHEMBL3675400
9.27	IC50	0.537	nM	STAUROSPORINE
9.26	IC50	0.55	nM	CHEMBL3675401
9.26	IC50	0.553	nM	STAUROSPORINE
9.24	IC50	0.58	nM	CHEMBL3675402
9.22	IC50	0.6	nM	CHEMBL3670404
9.22	IC50	0.6	nM	CHEMBL3670464
9.22	IC50	0.6	nM	CHEMBL3685329
9.22	IC50	0.6	nM	CHEMBL3904322
9.22	IC50	0.6	nM	CHEMBL3910789
9.22	IC50	0.6	nM	CHEMBL3919089
9.22	IC50	0.6	nM	CHEMBL3941283
9.21	IC50	0.61	nM	CHEMBL3675403
9.19	IC50	0.65	nM	CHEMBL3675404
9.18	IC50	0.66	nM	CHEMBL3675405
9.17	IC50	0.68	nM	CHEMBL3675406
9.17	IC50	0.68	nM	CHEMBL3675407
9.15	IC50	0.7	nM	CHEMBL3670495
9.15	IC50	0.7	nM	CHEMBL3965271
9.15	IC50	0.7	nM	CHEMBL3961056
9.15	IC50	0.7	nM	CHEMBL3891980
9.14	IC50	0.72	nM	CHEMBL3675408
9.14	IC50	0.73	nM	CHEMBL3957657
9.12	IC50	0.75	nM	CHEMBL2347053
9.10	IC50	0.79	nM	CHEMBL3675409
9.10	IC50	0.8	nM	CHEMBL3675410
9.10	IC50	0.8	nM	CHEMBL3966203

PubChem BioAssay actives

282 with measured affinity, of 2483 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
(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	1715234: Inhibition of human p70S6K using KKRNRTLTK as substrate by [gamma-33P]-ATP assay	ic50	0.0004	uM
4-[[(1S)-1-(3-fluorophenyl)-2-(methylamino)ethyl]amino]quinazoline-8-carboxamide	1771962: Inhibition of N-terminal His6-tagged human p70S6k T412E mutant (1 to 421 residues) expressed in Sf21 cells using FITC-AHA-AKRRRLSSLRA-OH as substrate incubated for 90 mins by mobility shift assay	ic50	0.0006	uM
4-[[(1S)-2-amino-1-phenylethyl]amino]quinazoline-8-carboxamide	1771962: Inhibition of N-terminal His6-tagged human p70S6k T412E mutant (1 to 421 residues) expressed in Sf21 cells using FITC-AHA-AKRRRLSSLRA-OH as substrate incubated for 90 mins by mobility shift assay	ic50	0.0008	uM
(3Z)-3-[[5-(2-nitrophenyl)-1H-pyrazol-4-yl]methylidene]-1H-indol-2-one	739585: Inhibition of p70S6K (unknown origin) after 10 mins by mobility shift assay	ic50	0.0008	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	659388: Displacement of fluorescent-ARC-583/ARC-1042/ARC-1059 from His6-tagged recombinant human p70S6K by fluorescence anisotropy assay	kd	0.0010	uM
2-(4-amino-1,2,5-oxadiazol-3-yl)-1-cyclobutylbenzimidazol-5-ol	468535: Inhibition of p70S6K assessed as decrease in NADH absorbance at 340 nm in the presence of	ki	0.0010	uM
4-(5-amino-1-cyclobutylbenzimidazol-2-yl)-1,2,5-oxadiazol-3-amine	468535: Inhibition of p70S6K assessed as decrease in NADH absorbance at 340 nm in the presence of	ki	0.0010	uM
N-[5-amino-1-[(4-methoxyphenyl)methyl]pyrazol-4-yl]-5-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]-2-methylbenzamide	578736: inhibition of p70S6K	ic50	0.0010	uM
4-[[1-(3-fluorophenyl)-2-(methylamino)ethyl]amino]quinazoline-8-carboxamide	1771962: Inhibition of N-terminal His6-tagged human p70S6k T412E mutant (1 to 421 residues) expressed in Sf21 cells using FITC-AHA-AKRRRLSSLRA-OH as substrate incubated for 90 mins by mobility shift assay	ic50	0.0010	uM
1-[3-[4-(3-bromo-2H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-5-(2-pyrrolidin-1-ylethylamino)phenyl]propan-1-one	656958: Inhibition of p70S6K after 3 hrs by luciferase based chemiluminescence assay	ic50	0.0010	uM
3-[4-(3-bromo-2H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-(2-methylpropoxy)-N-(2-pyrrolidin-1-ylethyl)aniline	656958: Inhibition of p70S6K after 3 hrs by luciferase based chemiluminescence assay	ic50	0.0010	uM
3-[4-(3-bromo-2H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-(3-methyl-1,2,4-oxadiazol-5-yl)-N-(2-pyrrolidin-1-ylethyl)aniline	656958: Inhibition of p70S6K after 3 hrs by luciferase based chemiluminescence assay	ic50	0.0010	uM
3-[4-(3-bromo-2H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-N-phenyl-5-(2-pyrrolidin-1-ylethylamino)benzamide	656958: Inhibition of p70S6K after 3 hrs by luciferase based chemiluminescence assay	ic50	0.0010	uM
4-[[(1S)-2-(azetidin-1-yl)-1-(3,4-difluorophenyl)ethyl]amino]quinazoline-8-carboxamide	1771962: Inhibition of N-terminal His6-tagged human p70S6k T412E mutant (1 to 421 residues) expressed in Sf21 cells using FITC-AHA-AKRRRLSSLRA-OH as substrate incubated for 90 mins by mobility shift assay	ic50	0.0010	uM
4-[[(1S)-2-(azetidin-1-yl)-1-[4-(trifluoromethyl)phenyl]ethyl]amino]quinazoline-8-carboxamide	1771962: Inhibition of N-terminal His6-tagged human p70S6k T412E mutant (1 to 421 residues) expressed in Sf21 cells using FITC-AHA-AKRRRLSSLRA-OH as substrate incubated for 90 mins by mobility shift assay	ic50	0.0010	uM
1-[(3-hydroxyphenyl)methyl]-3-(4-pyridin-4-yl-1,3-thiazol-2-yl)urea;methanesulfonic acid	1119791: Inhibition of p70S6K (unknown origin)	ic50	0.0010	uM
4-[[(1S)-2-(azetidin-1-yl)-1-[4-chloro-3-(trifluoromethyl)phenyl]ethyl]amino]quinazoline-8-carboxamide	1771962: Inhibition of N-terminal His6-tagged human p70S6k T412E mutant (1 to 421 residues) expressed in Sf21 cells using FITC-AHA-AKRRRLSSLRA-OH as substrate incubated for 90 mins by mobility shift assay	ic50	0.0011	uM
4-[[(1S)-2-(azetidin-1-yl)-1-(3-chlorophenyl)ethyl]amino]quinazoline-8-carboxamide	1771962: Inhibition of N-terminal His6-tagged human p70S6k T412E mutant (1 to 421 residues) expressed in Sf21 cells using FITC-AHA-AKRRRLSSLRA-OH as substrate incubated for 90 mins by mobility shift assay	ic50	0.0013	uM
4-[[(1S)-2-(azetidin-1-yl)-1-[3-(trifluoromethyl)phenyl]ethyl]amino]quinazoline-8-carboxamide	1771962: Inhibition of N-terminal His6-tagged human p70S6k T412E mutant (1 to 421 residues) expressed in Sf21 cells using FITC-AHA-AKRRRLSSLRA-OH as substrate incubated for 90 mins by mobility shift assay	ic50	0.0014	uM
4-[[4-(trifluoromethyl)phenyl]methylamino]quinazoline-8-carboxamide	1771962: Inhibition of N-terminal His6-tagged human p70S6k T412E mutant (1 to 421 residues) expressed in Sf21 cells using FITC-AHA-AKRRRLSSLRA-OH as substrate incubated for 90 mins by mobility shift assay	ic50	0.0020	uM
4-[[(1S)-1-(3-fluorophenyl)-2-(methylamino)ethyl]amino]-2-methylquinazoline-8-carboxamide	1771962: Inhibition of N-terminal His6-tagged human p70S6k T412E mutant (1 to 421 residues) expressed in Sf21 cells using FITC-AHA-AKRRRLSSLRA-OH as substrate incubated for 90 mins by mobility shift assay	ic50	0.0020	uM
2-ethyl-4-[[(1S)-1-(3-fluorophenyl)-2-(methylamino)ethyl]amino]quinazoline-8-carboxamide	1771962: Inhibition of N-terminal His6-tagged human p70S6k T412E mutant (1 to 421 residues) expressed in Sf21 cells using FITC-AHA-AKRRRLSSLRA-OH as substrate incubated for 90 mins by mobility shift assay	ic50	0.0020	uM
1-[3-[4-(3-bromo-2H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-5-(2-pyrrolidin-1-ylethylamino)phenyl]-4,4,4-trifluorobutan-1-one	656958: Inhibition of p70S6K after 3 hrs by luciferase based chemiluminescence assay	ic50	0.0020	uM
N-[5-chloro-3-[4-(3-ethyl-2H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methylphenyl]-N’,N’-dimethylethane-1,2-diamine	654034: Inhibition of human p70S6K D18H and T412E mutant using RRRLSSLRA as substrate after 3 hrs by luciferase-luciferin-coupled chemiluminescence assay	ic50	0.0020	uM
3-[4-(3-bromo-2H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-N-(2-pyrrolidin-1-ylethyl)-5-(2,2,2-trifluoroethoxymethyl)aniline	656958: Inhibition of p70S6K after 3 hrs by luciferase based chemiluminescence assay	ic50	0.0020	uM
methyl 3-[4-(3-bromo-2H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-5-(2-pyrrolidin-1-ylethylamino)benzoate	656958: Inhibition of p70S6K after 3 hrs by luciferase based chemiluminescence assay	ic50	0.0020	uM
4-[4-[5-chloro-2-methyl-3-(3-pyrrolidin-1-ylpropyl)phenyl]piperazin-1-yl]-3-ethyl-2H-pyrazolo[3,4-d]pyrimidine	654034: Inhibition of human p70S6K D18H and T412E mutant using RRRLSSLRA as substrate after 3 hrs by luciferase-luciferin-coupled chemiluminescence assay	ic50	0.0020	uM
3-[4-(3-bromo-2H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-(3,3-dimethylbutyl)-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline	656958: Inhibition of p70S6K after 3 hrs by luciferase based chemiluminescence assay	ic50	0.0020	uM
3-[4-(3-bromo-2H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-chloro-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline	656958: Inhibition of p70S6K after 3 hrs by luciferase based chemiluminescence assay	ic50	0.0020	uM
N-[3-[4-(3-bromo-2H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-chloro-2-methylphenyl]-N’,N’-dimethylethane-1,2-diamine	654034: Inhibition of human p70S6K D18H and T412E mutant using RRRLSSLRA as substrate after 3 hrs by luciferase-luciferin-coupled chemiluminescence assay	ic50	0.0020	uM
3-[4-(3-bromo-2H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-ethoxy-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline	656958: Inhibition of p70S6K after 3 hrs by luciferase based chemiluminescence assay	ic50	0.0020	uM
4-[[(1S)-2-(azetidin-1-yl)-1-(4-chloro-3-fluorophenyl)ethyl]amino]quinazoline-8-carboxamide	1771962: Inhibition of N-terminal His6-tagged human p70S6k T412E mutant (1 to 421 residues) expressed in Sf21 cells using FITC-AHA-AKRRRLSSLRA-OH as substrate incubated for 90 mins by mobility shift assay	ic50	0.0020	uM
4-[[(1S)-2-(azetidin-1-yl)-1-(3-fluorophenyl)ethyl]amino]quinazoline-8-carboxamide	1771962: Inhibition of N-terminal His6-tagged human p70S6k T412E mutant (1 to 421 residues) expressed in Sf21 cells using FITC-AHA-AKRRRLSSLRA-OH as substrate incubated for 90 mins by mobility shift assay	ic50	0.0024	uM
4-[[(1S)-2-(dimethylamino)-1-phenylethyl]amino]quinazoline-8-carboxamide	1771962: Inhibition of N-terminal His6-tagged human p70S6k T412E mutant (1 to 421 residues) expressed in Sf21 cells using FITC-AHA-AKRRRLSSLRA-OH as substrate incubated for 90 mins by mobility shift assay	ic50	0.0026	uM
4-[[2-(methylamino)-1-phenylethyl]amino]quinazoline-8-carboxamide	1771962: Inhibition of N-terminal His6-tagged human p70S6k T412E mutant (1 to 421 residues) expressed in Sf21 cells using FITC-AHA-AKRRRLSSLRA-OH as substrate incubated for 90 mins by mobility shift assay	ic50	0.0029	uM
4-[[(1S)-2-(azetidin-1-yl)-1-[4-fluoro-3-(trifluoromethyl)phenyl]ethyl]amino]quinazoline-8-carboxamide	1771962: Inhibition of N-terminal His6-tagged human p70S6k T412E mutant (1 to 421 residues) expressed in Sf21 cells using FITC-AHA-AKRRRLSSLRA-OH as substrate incubated for 90 mins by mobility shift assay	ic50	0.0029	uM
3-[5-chloro-3-[4-(3-ethyl-2H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methylphenyl]-N,N-diethylpropan-1-amine	654034: Inhibition of human p70S6K D18H and T412E mutant using RRRLSSLRA as substrate after 3 hrs by luciferase-luciferin-coupled chemiluminescence assay	ic50	0.0030	uM
5-chloro-3-[4-(3-ethyl-2H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline	654034: Inhibition of human p70S6K D18H and T412E mutant using RRRLSSLRA as substrate after 3 hrs by luciferase-luciferin-coupled chemiluminescence assay	ic50	0.0030	uM
N-[5-chloro-3-[4-(3-ethyl-2H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methylphenyl]-N’,N’-diethylethane-1,2-diamine	654034: Inhibition of human p70S6K D18H and T412E mutant using RRRLSSLRA as substrate after 3 hrs by luciferase-luciferin-coupled chemiluminescence assay	ic50	0.0030	uM
6-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-5-nitropyrimidin-4-amine	654034: Inhibition of human p70S6K D18H and T412E mutant using RRRLSSLRA as substrate after 3 hrs by luciferase-luciferin-coupled chemiluminescence assay	ic50	0.0030	uM
4-[4-[4-[4-fluoro-3-(trifluoromethyl)phenyl]-1-methylimidazol-2-yl]piperidin-1-yl]-1H-pyrazolo[5,4-d]pyrimidine	1495039: Inhibition of human p70S6K measured at apparent ATP Km level	ic50	0.0040	uM
4-(1-cyclobutylbenzimidazol-2-yl)-1,2,5-oxadiazol-3-amine	468535: Inhibition of p70S6K assessed as decrease in NADH absorbance at 340 nm in the presence of	ki	0.0040	uM
N-[5-chloro-2-methyl-3-[4-[3-(trifluoromethyl)-2H-pyrazolo[3,4-d]pyrimidin-4-yl]piperazin-1-yl]phenyl]-N’,N’-dimethylethane-1,2-diamine	654034: Inhibition of human p70S6K D18H and T412E mutant using RRRLSSLRA as substrate after 3 hrs by luciferase-luciferin-coupled chemiluminescence assay	ic50	0.0040	uM
4-[4-[5-chloro-2-methyl-3-(2-pyrrolidin-1-ylethoxy)phenyl]piperazin-1-yl]-3-ethyl-2H-pyrazolo[3,4-d]pyrimidine	654034: Inhibition of human p70S6K D18H and T412E mutant using RRRLSSLRA as substrate after 3 hrs by luciferase-luciferin-coupled chemiluminescence assay	ic50	0.0050	uM
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-propyl-2H-pyrazolo[3,4-d]pyrimidine	654034: Inhibition of human p70S6K D18H and T412E mutant using RRRLSSLRA as substrate after 3 hrs by luciferase-luciferin-coupled chemiluminescence assay	ic50	0.0060	uM
4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-ethyl-2H-pyrazolo[3,4-d]pyrimidine	654034: Inhibition of human p70S6K D18H and T412E mutant using RRRLSSLRA as substrate after 3 hrs by luciferase-luciferin-coupled chemiluminescence assay	ic50	0.0060	uM
2-[5-chloro-3-[4-(3-ethyl-2H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methylphenoxy]-N,N-dimethylethanamine	654034: Inhibition of human p70S6K D18H and T412E mutant using RRRLSSLRA as substrate after 3 hrs by luciferase-luciferin-coupled chemiluminescence assay	ic50	0.0060	uM
4-[[(1S)-2-(azetidin-1-yl)-1-phenylethyl]amino]quinazoline-8-carboxamide	1771962: Inhibition of N-terminal His6-tagged human p70S6k T412E mutant (1 to 421 residues) expressed in Sf21 cells using FITC-AHA-AKRRRLSSLRA-OH as substrate incubated for 90 mins by mobility shift assay	ic50	0.0062	uM
5-chloro-4-(4-chloro-1-methylpyrazol-5-yl)-N-[(3S,4S)-4-(3,4-difluorophenyl)piperidin-3-yl]furan-2-carboxamide;(2R,3R)-2,3-dihydroxybutanedioic acid	1608045: Inhibition of human P70S6K by mobility shift assay	ic50	0.0070	uM
(2S)-1-[[6-(furan-3-yl)-5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-(1H-indol-3-yl)propan-2-amine	454239: Inhibition of P70S6K	ic50	0.0070	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Sirolimus	affects cotreatment, decreases reaction, increases phosphorylation, decreases phosphorylation, increases activity (+7 more)	54
Resveratrol	decreases phosphorylation, decreases reaction, decreases expression, increases abundance, increases phosphorylation (+4 more)	17
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	increases expression, decreases phosphorylation, increases reaction, affects cotreatment, increases activity (+3 more)	13
sodium arsenite	decreases phosphorylation, affects cotreatment, increases abundance, decreases reaction, increases phosphorylation (+2 more)	7
U 0126	affects cotreatment, decreases phosphorylation, decreases reaction, increases activity, increases reaction (+2 more)	7
Cadmium Chloride	decreases phosphorylation, affects reaction, decreases reaction, increases activity, increases phosphorylation	7
Arsenic Trioxide	decreases reaction, increases phosphorylation, decreases activity, decreases expression, decreases phosphorylation	6
Oxygen	increases reaction, decreases reaction, increases phosphorylation, affects cotreatment, decreases phosphorylation	5
dorsomorphin	decreases reaction, decreases phosphorylation, increases reaction, decreases expression, increases abundance (+2 more)	4
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases phosphorylation, increases response to substance, affects cotreatment	4
Quercetin	decreases reaction, increases phosphorylation, decreases activity, decreases phosphorylation, increases reaction (+2 more)	4
cyanoginosin LR	decreases reaction, increases phosphorylation, increases expression, increases reaction	3
1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo(h)(1,6)naphthyridin-2(1H)-one	decreases phosphorylation	3
Wortmannin	increases phosphorylation, decreases phosphorylation, decreases reaction, increases expression, affects cotreatment (+1 more)	3
Curcumin	decreases reaction, increases phosphorylation, decreases phosphorylation	3
Dexamethasone	affects reaction, affects cotreatment, affects phosphorylation, decreases reaction, increases phosphorylation (+1 more)	3
Estradiol	decreases reaction, increases phosphorylation, affects cotreatment, increases expression	3
Hydrogen Peroxide	increases reaction, decreases phosphorylation, increases expression, decreases reaction, increases phosphorylation	3
Metformin	decreases expression, affects cotreatment, decreases reaction, increases phosphorylation	3
Tretinoin	decreases expression	3
ON123300	decreases phosphorylation	2
gingerenone A	decreases activity, decreases phosphorylation, increases response to substance	2
bisphenol A	increases phosphorylation	2
arsenite	increases abundance, decreases reaction, increases phosphorylation	2
cordycepin	increases phosphorylation, affects cotreatment, decreases phosphorylation	2
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases phosphorylation	2
deguelin	decreases expression, decreases phosphorylation	2
temsirolimus	decreases phosphorylation, increases reaction	2
pyrazolanthrone	decreases activity, decreases reaction, increases phosphorylation	2
quinocetone	decreases phosphorylation, increases reaction, decreases response to substance, increases phosphorylation	2

ChEMBL screening assays

585 unique, capped per target: 582 binding, 2 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL803651	Binding	Inhibition of p70S6K in presence of 10 uM ATP	5-aryl-pyrazolo[3,4-b]pyridines: potent inhibitors of glycogen synthase kinase-3 (GSK-3). — Bioorg Med Chem Lett
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
CHEMBL1963708	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: RPS6KB1	PubChem BioAssay data set

Cellosaurus cell lines

2 cell lines: 1 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9R0	Ubigene HEK293 RPS6KB1 KO	Transformed cell line	Female
CVCL_TJ69	HAP1 RPS6KB1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00879060	PHASE4	COMPLETED	Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy
NCT01721967	PHASE4	COMPLETED	Ranolazine for the Treatment of Chest Pain in HCM Patients
NCT02948998	PHASE4	UNKNOWN	Evaluating the Effect of Spironolactone on Hypertrophic Cardiomyopathy
NCT03249272	PHASE4	TERMINATED	Microvascular Dysfunction in Nonischemic Cardiomyopathy: Insights From CMR Assessment of Coronary Flow Reserve
NCT04133532	PHASE4	COMPLETED	Effect of Metoprolol in Post Alcohol Septal Ablation Patients With Hypertrophic Cardiomyopathy
NCT06401343	PHASE4	RECRUITING	Use of SGLT2i in noHCM With HFpEF
NCT07103655	PHASE4	NOT_YET_RECRUITING	The Therapeutic Value of Mavacamten in Hypertrophic Cardiomyopathy With Mid-to-Apical Left Ventricular Obstruction
NCT07600177	PHASE4	RECRUITING	Mavacamten to Aficamten Transition in Patients With Obstructive Hypertrophic Cardiomyopathy
NCT00317967	PHASE3	COMPLETED	Study to Determine if Atorvastatin Reduces Size and Stiffness of Muscle in the Left Ventricle of the Heart
NCT00698074	PHASE3	UNKNOWN	Diastolic Ventricular Interaction and the Effects of Biventricular Pacing in Hypertrophic Cardiomyopathy
NCT00821353	PHASE3	COMPLETED	Antiarrhythmic Therapy Versus Catheter Ablation for Atrial Fibrillation in Hypertrophic Cardiomyopathy
NCT02431221	PHASE3	WITHDRAWN	Efficacy, Safety, and Tolerability of Perhexiline in Subjects With Hypertrophic Cardiomyopathy and Heart Failure
NCT03470545	PHASE3	COMPLETED	Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy
NCT05174416	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Mavacamten in Chinese Adults With Symptomatic Obstructive HCM
NCT05182658	PHASE3	ACTIVE_NOT_RECRUITING	Empagliflozin in Hypertrophic Cardiomyopathy
NCT05186818	PHASE3	COMPLETED	Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM
NCT05767346	PHASE3	COMPLETED	Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol Succinate in Adults With Symptomatic oHCM
NCT06116968	PHASE3	COMPLETED	An Open-Label Study of Aficamten for Chinese Patients With Symptomatic oHCM
NCT06873828	PHASE3	NOT_YET_RECRUITING	Evaluation of the Efficacy and Safety of Wearable ECG (AT-Patch) in Patients With Hypertrophic Cardiomyopathy Requiring 48-Hour Holter MonitoringEvaluation of the Efficacy and Safety of Wearable ECG (AT-Patch) in Patients With Hypertrophic Cardiomyopathy Requiring 48-Hour Holter Monitoring
NCT07021976	PHASE3	RECRUITING	A Phase III Trial of HRS-1893 in Patients With Obstructive Hypertrophic Cardiomyopathy
NCT07023341	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Learn More About How Well Aficamten Works in Japanese Participants With Symptomatic Obstructive Hypertrophic Cardiomyopathy
NCT07202897	PHASE3	NOT_YET_RECRUITING	LA-HCM Study : Rivaroxaban for Antithrombotic Prevention in Hypertrophic Cardiomyopathy Patients With Abnormal Left Atrial Strain.
NCT00001631	PHASE2	COMPLETED	Study of Blood Flow in Heart Muscle
NCT00001894	PHASE2	COMPLETED	A Comparison of Two Treatments: Pacemaker and Percutaneous Transluminal Septal Ablation for Hypertrophic Cardiomyopathy
NCT00001960	PHASE2	COMPLETED	Studying the Effectiveness of Pacemaker Therapy in Children Who Have Thickened Heart Muscle
NCT00011076	PHASE2	COMPLETED	Pirfenidone to Treat Hypertrophic Cardiomyopathy
NCT00035386	PHASE2	COMPLETED	Alcohol Septal Ablation in Obstructive Hypertrophic Cardiomyopathy: A Pilot Study
NCT00430833	PHASE2	UNKNOWN	CHANCE - Candesartan in Hypertrophic Cardiomyopathy
NCT00500552	PHASE2	COMPLETED	Perhexiline Therapy in Patients With Hypertrophic Cardiomyopathy
NCT01150461	PHASE2	COMPLETED	Effect of Losartan in Patients With Nonobstructive Hypertrophic Cardiomyopathy
NCT01230918	PHASE2	TERMINATED	Study to Develop a Non-invasive Marker for Monitoring Myocardial Fibrosis
NCT01447654	PHASE2	COMPLETED	Inhibition of the Renin Angiotensin System With Losartan in Patients With Hypertrophic Cardiomyopathy
NCT01696370	PHASE2	UNKNOWN	Trimetazidine Therapy in Hypertrophic Cardiomyopathy
NCT01912534	PHASE2	COMPLETED	Valsartan for Attenuating Disease Evolution In Early Sarcomeric HCM
NCT02590809	PHASE2	COMPLETED	Hypertrophic Cardiomyopathy Symptom Release by BX1514M
NCT03496168	PHASE2	COMPLETED	Extension Study of Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Previously Enrolled in PIONEER
NCT03532802	PHASE2	COMPLETED	The Effect of Metoprolol in Patients With Hypertrophic Obstructive Cardiomyopathy.
NCT03832660	PHASE2	COMPLETED	Sacubitril/Valsartan vs Lifestyle in Hypertrophic Cardiomyopathy
NCT04219826	PHASE2	COMPLETED	Dose-finding Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CK-3773274 in Adults With Hypertrophic Cardiomyopathy
NCT04426578	PHASE2	UNKNOWN	Role of Perhexiline in Hypertrophic Cardiomyopathy