Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT4D1LN)

• DOT Name: Small ribosomal subunit protein eS6 (RPS6)
• Synonyms: 40S ribosomal protein S6; Phosphoprotein NP33
• Gene Name: RPS6
• Related Disease:
  Acute myelogenous leukaemia
  Stomach cancer
  Alzheimer disease
  Autism spectrum disorder
  B-cell lymphoma
  B-cell neoplasm
  Breast neoplasm
  Carcinoma
  Cardiovascular disease
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Diabetic kidney disease
  Esophageal squamous cell carcinoma
  Gastric neoplasm
  Glioblastoma multiforme
  Glioma
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Hereditary diffuse gastric adenocarcinoma
  Intellectual disability
  Leukemia
  Liver failure
  Lung adenocarcinoma
  Multiple sclerosis
  Neoplasm
  Non-small-cell lung cancer
  Parkinson disease
  Prostate neoplasm
  Renal cell carcinoma
  Sarcoma
  Squamous cell carcinoma
  Systemic lupus erythematosus
  Tuberous sclerosis
  Type-1/2 diabetes
  Vascular dementia
  Advanced cancer
  High blood pressure
  Adult glioblastoma
  Astrocytoma
  Breast cancer
  Breast carcinoma
  Coffin-Lowry syndrome
  Gastric cancer
  Melanoma
  Prostate cancer
  Prostate carcinoma
• UniProt ID: RS6_HUMAN
• PDB ID: 4UG0 ; 4V6X ; 5A2Q ; 5AJ0 ; 5FLX ; 5LKS ; 5OA3 ; 5T2C ; 5VYC ; 6F4P ; 6F4Q ; 6FEC ; 6G18 ; 6G4S ; 6G4W ; 6G51 ; 6G53 ; 6G5H ; 6G5I ; 6IP5 ; 6IP6 ; 6IP8 ; 6OLE ; 6OLF ; 6OLG ; 6OLI ; 6OLZ ; 6OM0 ; 6OM7 ; 6QZP ; 6XA1 ; 6Y0G ; 6Y2L ; 6Y57 ; 6YBW ; 6Z6L ; 6Z6M ; 6Z6N ; 6ZLW ; 6ZM7 ; 6ZME ; 6ZMI ; 6ZMO ; 6ZMT ; 6ZMW ; 6ZN5 ; 6ZOJ ; 6ZOK ; 6ZON ; 6ZP4 ; 6ZUO ; 6ZV6 ; 6ZVH ; 6ZVJ ; 6ZXD ; 6ZXE ; 6ZXF ; 6ZXG ; 6ZXH ; 7A09 ; 7K5I ; 7MQ8 ; 7MQ9 ; 7MQA ; 7QP6 ; 7QP7 ; 7QVP ; 7R4X ; 7TQL ; 7WTS ; 7WTT ; 7WTU ; 7WTV ; 7WTW ; 7WTX ; 7WTZ ; 7WU0 ; 7XNX ; 7XNY ; 7ZJW ; 7ZJX ; 8G5Y ; 8G5Z ; 8G60 ; 8G61 ; 8G6J ; 8GLP ; 8JDJ ; 8JDK ; 8JDL ; 8JDM ; 8PPK ; 8PPL ; 8T4S
• Pfam ID: PF01092
• Sequence:
  MKLNISFPATGCQKLIEVDDERKLRTFYEKRMATEVAADALGEEWKGYVVRISGGNDKQG
  FPMKQGVLTHGRVRLLLSKGHSCYRPRRTGERKRKSVRGCIVDANLSVLNLVIVKKGEKD
  IPGLTDTTVPRRLGPKRASRIRKLFNLSKEDDVRQYVVRKPLNKEGKKPRTKAPKIQRLV
  TPRVLQHKRRRIALKKQRTKKNKEEAAEYAKLLAKRMKEAKEKRQEQIAKRRRLSSLRAS
  TSKSESSQK
• Function: Component of the 40S small ribosomal subunit. Plays an important role in controlling cell growth and proliferation through the selective translation of particular classes of mRNA. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.
• KEGG Pathway:
  EGFR tyrosine ki.se inhibitor resistance (hsa01521)
  Ribosome (hsa03010)
  HIF-1 sig.ling pathway (hsa04066)
  mTOR sig.ling pathway (hsa04150)
  PI3K-Akt sig.ling pathway (hsa04151)
  Apelin sig.ling pathway (hsa04371)
  Thermogenesis (hsa04714)
  Insulin sig.ling pathway (hsa04910)
  Coro.virus disease - COVID-19 (hsa05171)
  Proteoglycans in cancer (hsa05205)
• Reactome Pathway:
  Peptide chain elongation (R-HSA-156902)
  mTORC1-mediated signalling (R-HSA-166208)
  SRP-dependent cotranslational protein targeting to membrane (R-HSA-1799339)
  Viral mRNA Translation (R-HSA-192823)
  Selenocysteine synthesis (R-HSA-2408557)
  rRNA modification in the nucleus and cytosol (R-HSA-6790901)
  Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226)
  Translation initiation complex formation (R-HSA-72649)
  Formation of a pool of free 40S subunits (R-HSA-72689)
  Formation of the ternary complex, and subsequently, the 43S complex (R-HSA-72695)
  Ribosomal scanning and start codon recognition (R-HSA-72702)
  GTP hydrolysis and joining of the 60S ribosomal subunit (R-HSA-72706)
  Eukaryotic Translation Termination (R-HSA-72764)
  Regulation of expression of SLITs and ROBOs (R-HSA-9010553)
  Protein hydroxylation (R-HSA-9629569)
  Response of EIF2AK4 (GCN2) to amino acid deficiency (R-HSA-9633012)
  Nuclear events stimulated by ALK signaling in cancer (R-HSA-9725371)
  SARS-CoV-1 modulates host translation machinery (R-HSA-9735869)
  SARS-CoV-2 modulates host translation machinery (R-HSA-9754678)
  Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) (R-HSA-975956)
  Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) (R-HSA-975957)
  L13a-mediated translational silencing of Ceruloplasmin expression (R-HSA-156827)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Altered Expression	[1]
Stomach cancer	DISKIJSX	Definitive	Altered Expression	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[4]
B-cell lymphoma	DISIH1YQ	Strong	Altered Expression	[5]
B-cell neoplasm	DISVY326	Strong	Biomarker	[6]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[7]
Carcinoma	DISH9F1N	Strong	Biomarker	[8]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[9]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[10]
Colon cancer	DISVC52G	Strong	Altered Expression	[11]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[11]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[12]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[13]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Posttranslational Modification	[14]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[15]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[16]
Glioma	DIS5RPEH	Strong	Biomarker	[17]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[18]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[19]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Strong	Biomarker	[15]
Intellectual disability	DISMBNXP	Strong	Biomarker	[20]
Leukemia	DISNAKFL	Strong	Biomarker	[21]
Liver failure	DISLGEL6	Strong	Biomarker	[22]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[23]
Multiple sclerosis	DISB2WZI	Strong	Altered Expression	[24]
Neoplasm	DISZKGEW	Strong	Biomarker	[25]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[26]
Parkinson disease	DISQVHKL	Strong	Altered Expression	[27]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[28]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[10]
Sarcoma	DISZDG3U	Strong	Altered Expression	[29]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[30]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[13]
Tuberous sclerosis	DISEMUGZ	Strong	Altered Expression	[31]
Type-1/2 diabetes	DISIUHAP	Strong	Altered Expression	[32]
Vascular dementia	DISVO82H	Strong	Therapeutic	[33]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[34]
High blood pressure	DISY2OHH	moderate	Altered Expression	[35]
Adult glioblastoma	DISVP4LU	Limited	Biomarker	[36]
Astrocytoma	DISL3V18	Limited	Biomarker	[16]
Breast cancer	DIS7DPX1	Limited	Biomarker	[37]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[37]
Coffin-Lowry syndrome	DISMTBDA	Limited	Genetic Variation	[38]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[2]
Melanoma	DIS1RRCY	Limited	Genetic Variation	[39]
Prostate cancer	DISF190Y	Limited	Biomarker	[40]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[40]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Artesunate	DMR27C8	Approved	Small ribosomal subunit protein eS6 (RPS6) decreases the response to substance of Artesunate.	[103]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Small ribosomal subunit protein eS6 (RPS6).	[41]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Small ribosomal subunit protein eS6 (RPS6).	[42]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Small ribosomal subunit protein eS6 (RPS6).	[43]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Small ribosomal subunit protein eS6 (RPS6).	[44]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Small ribosomal subunit protein eS6 (RPS6).	[45]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Small ribosomal subunit protein eS6 (RPS6).	[48]
Pioglitazone	DMKJ485	Approved	Pioglitazone decreases the expression of Small ribosomal subunit protein eS6 (RPS6).	[55]
Loratadine	DMF3AN7	Approved	Loratadine decreases the expression of Small ribosomal subunit protein eS6 (RPS6).	[63]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the activity of Small ribosomal subunit protein eS6 (RPS6).	[68]
Bardoxolone methyl	DMODA2X	Phase 3	Bardoxolone methyl decreases the expression of Small ribosomal subunit protein eS6 (RPS6).	[71]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin decreases the expression of Small ribosomal subunit protein eS6 (RPS6).	[73]
Tetrandrine	DMAOJBX	Phase 1	Tetrandrine decreases the expression of Small ribosomal subunit protein eS6 (RPS6).	[81]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Small ribosomal subunit protein eS6 (RPS6).	[84]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Small ribosomal subunit protein eS6 (RPS6).	[85]
Terfenadine	DM4KLPT	Withdrawn from market	Terfenadine decreases the expression of Small ribosomal subunit protein eS6 (RPS6).	[63]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Small ribosomal subunit protein eS6 (RPS6).	[87]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Small ribosomal subunit protein eS6 (RPS6).	[88]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Small ribosomal subunit protein eS6 (RPS6).	[90]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Small ribosomal subunit protein eS6 (RPS6).	[91]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug decreases the expression of Small ribosomal subunit protein eS6 (RPS6).	[94]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl affects the expression of Small ribosomal subunit protein eS6 (RPS6).	[95]
torin 1	DMZD0NA	Investigative	torin 1 decreases the expression of Small ribosomal subunit protein eS6 (RPS6).	[94]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[46]
Testosterone	DM7HUNW	Approved	Testosterone increases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[47]
Niclosamide	DMJAGXQ	Approved	Niclosamide affects the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[49]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[50]
Aspirin	DM672AH	Approved	Aspirin decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[51]
Etoposide	DMNH3PG	Approved	Etoposide increases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[52]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[53]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[54]
Sorafenib	DMS8IFC	Approved	Sorafenib decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[56]
Imatinib	DM7RJXL	Approved	Imatinib decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[57]
Cholecalciferol	DMGU74E	Approved	Cholecalciferol decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[51]
Glucosamine	DM4ZLFD	Approved	Glucosamine decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[59]
Eicosapentaenoic acid/docosa-hexaenoic acid	DMMUCG4	Approved	Eicosapentaenoic acid/docosa-hexaenoic acid decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[60]
2-deoxyglucose	DMIAHVU	Approved	2-deoxyglucose decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[51]
Crizotinib	DM4F29C	Approved	Crizotinib decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[61]
Vandetanib	DMRICNP	Approved	Vandetanib decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[62]
Letrozole	DMH07Y3	Approved	Letrozole decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[64]
SR141716A	DMCO5JZ	Approved	SR141716A decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[65]
AZD5363	DM9SKW8	Approved	AZD5363 decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[66]
Sotorasib	DMLSV74	Approved	Sotorasib decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[67]
Berberine	DMC5Q8X	Phase 4	Berberine decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[51]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[69]
Rigosertib	DMOSTXF	Phase 3	Rigosertib decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[70]
Buparlisib	DM1WEHC	Phase 3	Buparlisib decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[72]
AZD4547	DM3827C	Phase 2/3	AZD4547 decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[66]
PD-0325901	DM27D4J	Phase 2	PD-0325901 decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[74]
ANW-32821	DMMJOZD	Phase 2	ANW-32821 increases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[75]
GDC0941	DM1YAK6	Phase 2	GDC0941 decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[76]
BEZ235	DMKBRDL	Phase 2	BEZ235 decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[77]
MK-2206	DMT1OZ6	Phase 2	MK-2206 decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[78]
PF-04691502	DMS610L	Phase 2	PF-04691502 decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[74]
Azd2014	DMOEARH	Phase 2	Azd2014 decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[66]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[79]
LY294002	DMY1AFS	Phase 1	LY294002 decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[80]
VS-5584	DMMO3G5	Phase 1	VS-5584 decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[82]
GSK2126458	DMM7ZXR	Phase 1	GSK2126458 decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[83]
ZSTK474	DMVIMQX	Phase 1	ZSTK474 decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[70]
Methylthioadenosine	DMC8J6F	Terminated	Methylthioadenosine decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[86]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[89]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[92]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[93]
Microcystin-LR	DMTMLRN	Investigative	Microcystin-LR increases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[96]
U0126	DM31OGF	Investigative	U0126 decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[97]
Dorsomorphin	DMKYXJW	Investigative	Dorsomorphin increases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[98]
ABBV-744	DMTEA9C	Investigative	ABBV-744 decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[99]
Alpha-ketoglutaric acid	DM5LFYN	Investigative	Alpha-ketoglutaric acid increases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[100]
Silmitasertib	DMQIBZD	Investigative	Silmitasertib decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[101]
EPZ015666	DM3INX7	Investigative	EPZ015666 decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[86]
PHA-665752	DMCGX9U	Investigative	PHA-665752 decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[102]
BAG956	DMWC34B	Investigative	BAG956 decreases the phosphorylation of Small ribosomal subunit protein eS6 (RPS6).	[78]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Dihydroartemisinin	DMBXVMZ	Approved	Dihydroartemisinin affects the binding of Small ribosomal subunit protein eS6 (RPS6).	[58]

References

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