Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAELNGX)

DOT Name	Ribosomal protein S6 kinase beta-1 (RPS6KB1)
Synonyms	S6K-beta-1; S6K1; EC 2.7.11.1; 70 kDa ribosomal protein S6 kinase 1; P70S6K1; p70-S6K 1; Ribosomal protein S6 kinase I; Serine/threonine-protein kinase 14A; p70 ribosomal S6 kinase alpha; p70 S6 kinase alpha; p70 S6K-alpha; p70 S6KA
Gene Name	RPS6KB1
Related Disease	Hypertrophic cardiomyopathy ( )
UniProt ID	KS6B1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	3A60; 3A61; 3A62; 3WE4; 3WF5; 3WF6; 3WF7; 3WF8; 3WF9; 4L3J; 4L3L; 4L42; 4L43; 4L44; 4L45; 4L46; 4RLO; 4RLP; 5WBH; 5WBK; 7N91; 7N93
EC Number	2.7.11.1
Pfam ID	PF00069 ; PF00433
Sequence	MRRRRRRDGFYPAPDFRDREAEDMAGVFDIDLDQPEDAGSEDELEEGGQLNESMDHGGVG PYELGMEHCEKFEISETSVNRGPEKIRPECFELLRVLGKGGYGKVFQVRKVTGANTGKIF AMKVLKKAMIVRNAKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYLILEYLSGGEL FMQLEREGIFMEDTACFYLAEISMALGHLHQKGIIYRDLKPENIMLNHQGHVKLTDFGLC KESIHDGTVTHTFCGTIEYMAPEILMRSGHNRAVDWWSLGALMYDMLTGAPPFTGENRKK TIDKILKCKLNLPPYLTQEARDLLKKLLKRNAASRLGAGPGDAGEVQAHPFFRHINWEEL LARKVEPPFKPLLQSEEDVSQFDSKFTRQTPVDSPDDSTLSESANQVFLGFTYVAPSVLE SVKEKFSFEPKIRSPRRFIGSPRTPVSPVKFSPGDFWGRGASASTANPQTPVEYPMETSG IEQMDVTMSGEASAPLPIRQPNSGPYKKQAFPMISKRPEHLRMNL
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 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-alpha-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.
Tissue Specificity	Widely expressed.
KEGG Pathway	EGFR tyrosine ki.se inhibitor resistance (hsa01521 ) Endocrine resistance (hsa01522 ) ErbB sig.ling pathway (hsa04012 ) HIF-1 sig.ling pathway (hsa04066 ) Autophagy - animal (hsa04140 ) mTOR sig.ling pathway (hsa04150 ) PI3K-Akt sig.ling pathway (hsa04151 ) AMPK sig.ling pathway (hsa04152 ) Longevity regulating pathway (hsa04211 ) Longevity regulating pathway - multiple species (hsa04213 ) TGF-beta sig.ling pathway (hsa04350 ) Apelin sig.ling pathway (hsa04371 ) Fc gamma R-mediated phagocytosis (hsa04666 ) Thermogenesis (hsa04714 ) Insulin sig.ling pathway (hsa04910 ) Insulin resistance (hsa04931 ) Shigellosis (hsa05131 ) Human cytomegalovirus infection (hsa05163 ) Human papillomavirus infection (hsa05165 ) Human immunodeficiency virus 1 infection (hsa05170 ) Pathways in cancer (hsa05200 ) Proteoglycans in cancer (hsa05205 ) Chemical carcinogenesis - receptor activation (hsa05207 ) Colorectal cancer (hsa05210 ) Pancreatic cancer (hsa05212 ) Acute myeloid leukemia (hsa05221 ) Breast cancer (hsa05224 ) Hepatocellular carcinoma (hsa05225 ) Gastric cancer (hsa05226 ) Choline metabolism in cancer (hsa05231 ) PD-L1 expression and PD-1 checkpoint pathway in cancer (hsa05235 )
Reactome Pathway	mTORC1-mediated signalling (R-HSA-166208 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance		REF
Hypertrophic cardiomyopathy	DISQG2AI	Limited	Autosomal dominant	[1]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

38 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the activity of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the activity of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[9]
Testosterone	DM7HUNW	Approved	Testosterone increases the activity of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[11]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[12]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[15]
Imatinib	DM7RJXL	Approved	Imatinib decreases the expression of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[24]
Romiplostim	DM3U7SZ	Approved	Romiplostim decreases the activity of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[35]
Momelotinib	DMF98Q0	Approved	Momelotinib decreases the expression of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[36]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the activity of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[39]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[3]
URSOLIC ACID	DM4SOAW	Phase 2	URSOLIC ACID decreases the expression of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[49]
LY294002	DMY1AFS	Phase 1	LY294002 decreases the expression of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[53]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[57]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[58]
Dioscin	DM5H2W9	Preclinical	Dioscin decreases the expression of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[62]
EHT-1864	DMYAMP5	Terminated	EHT-1864 decreases the expression of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[64]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[66]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[67]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the activity of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[69]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[70]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[73]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug decreases the activity of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[75]
acrolein	DMAMCSR	Investigative	acrolein decreases the expression of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[76]
Microcystin-LR	DMTMLRN	Investigative	Microcystin-LR increases the expression of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[77]
OXYBENZONE	DMMZYX6	Investigative	OXYBENZONE increases the expression of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[78]
Apigenin	DMI3491	Investigative	Apigenin decreases the expression of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[79]
Morin	DM2OGZ5	Investigative	Morin increases the expression of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[80]
LICOAGROCHACONE A	DMWY0TN	Investigative	LICOAGROCHACONE A decreases the expression of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[82]
gingerol	DMNXYSM	Investigative	gingerol decreases the expression of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[83]
2,6-Dihydroanthra/1,9-Cd/Pyrazol-6-One	DMDN12L	Investigative	2,6-Dihydroanthra/1,9-Cd/Pyrazol-6-One decreases the activity of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[85]
DIECKOL	DMBCK4G	Investigative	DIECKOL decreases the expression of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[86]
H-89	DM4RVGO	Investigative	H-89 decreases the activity of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[8]
Fasudil	DMTCNOM	Investigative	Fasudil decreases the activity of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[8]
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⏷ Show the Full List of 38 Drug(s)

62 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[10]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[13]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[14]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[16]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[17]
Nicotine	DMWX5CO	Approved	Nicotine increases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[18]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[19]
Daunorubicin	DMQUSBT	Approved	Daunorubicin increases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[20]
Pioglitazone	DMKJ485	Approved	Pioglitazone decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[21]
Sorafenib	DMS8IFC	Approved	Sorafenib decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[22]
Gefitinib	DM15F0X	Approved	Gefitinib decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[23]
Sertraline	DM0FB1J	Approved	Sertraline decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[25]
Cholecalciferol	DMGU74E	Approved	Cholecalciferol decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[26]
Dopamine	DMPGUCF	Approved	Dopamine decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[27]
Glucosamine	DM4ZLFD	Approved	Glucosamine decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[28]
Adenosine	DMM2NSK	Approved	Adenosine increases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[29]
2-deoxyglucose	DMIAHVU	Approved	2-deoxyglucose decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[30]
Teriflunomide	DMQ2FKJ	Approved	Teriflunomide decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[31]
Epirubicin	DMPDW6T	Approved	Epirubicin increases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[32]
Digitoxin	DMWVIGP	Approved	Digitoxin decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[33]
Trametinib	DM2JGQ3	Approved	Trametinib decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[34]
Benzocaine	DMI18HW	Approved	Benzocaine decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[37]
Penfluridol	DMG1DTE	Approved	Penfluridol decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[38]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[40]
Coprexa	DMA0WEK	Phase 3	Coprexa decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[41]
Bardoxolone methyl	DMODA2X	Phase 3	Bardoxolone methyl decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[42]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[43]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[44]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[45]
PEITC	DMOMN31	Phase 2	PEITC decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[46]
Puerarin	DMJIMXH	Phase 2	Puerarin increases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[47]
GDC0941	DM1YAK6	Phase 2	GDC0941 decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[48]
BEZ235	DMKBRDL	Phase 2	BEZ235 decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[50]
INK128	DMGO7QT	Phase 2	INK128 decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[51]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[52]
GSK618334	DMJPXZ4	Phase 1	GSK618334 decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[54]
Adaphostin	DM16QSG	Phase 1	Adaphostin decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[55]
GSK2126458	DMM7ZXR	Phase 1	GSK2126458 decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[50]
BMS-754807	DMPK32V	Phase 1	BMS-754807 decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[56]
ERA-923	DM6NTAS	Discontinued in Phase 2	ERA-923 decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[59]
AZD8055	DM7L8SG	Discontinued in Phase 1/2	AZD8055 decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[60]
MG-132	DMKA2YS	Preclinical	MG-132 decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[61]
Wortmannin	DM8EVK5	Terminated	Wortmannin decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[63]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[65]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[68]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[71]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[72]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[74]
Cordycepin	DM72Y01	Investigative	Cordycepin increases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[29]
BRN-3548355	DM4KXT0	Investigative	BRN-3548355 increases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[18]
Galangin	DM5TQ2O	Investigative	Galangin decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[81]
USNIC ACID	DMGOURX	Investigative	USNIC ACID decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[84]
Tetramethylbutylphenol	DMW9CH2	Investigative	Tetramethylbutylphenol increases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[65]
Sulfate	DMW0ZBF	Investigative	Sulfate affects the methylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[87]
LPA	DMI5XR1	Investigative	LPA increases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[88]
Fascaplysin	DMG5OZP	Investigative	Fascaplysin decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[89]
Alpha-ketoglutaric acid	DM5LFYN	Investigative	Alpha-ketoglutaric acid increases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[90]
Diamide	DMOCQ9J	Investigative	Diamide increases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[30]
torin 1	DMZD0NA	Investigative	torin 1 decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[22]
Thiorphan	DM86LFB	Investigative	Thiorphan decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[91]
Indatraline	DMIP9DN	Investigative	Indatraline decreases the phosphorylation of Ribosomal protein S6 kinase beta-1 (RPS6KB1).	[25]
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⏷ Show the Full List of 62 Drug(s)

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