Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNO82CU)

• DOT Name: Insulin receptor substrate 1 (IRS1)
• Synonyms: IRS-1
• Gene Name: IRS1
• UniProt ID: IRS1_HUMAN
• PDB ID: 1IRS; 1K3A; 1QQG; 2Z8C; 5U1M; 6BNT; 7PPL; 7PPM
• Pfam ID: PF02174 ; PF00169
• Sequence:
  MASPPESDGFSDVRKVGYLRKPKSMHKRFFVLRAASEAGGPARLEYYENEKKWRHKSSAP
  KRSIPLESCFNINKRADSKNKHLVALYTRDEHFAIAADSEAEQDSWYQALLQLHNRAKGH
  HDGAAALGAGGGGGSCSGSSGLGEAGEDLSYGDVPPGPAFKEVWQVILKPKGLGQTKNLI
  GIYRLCLTSKTISFVKLNSEAAAVVLQLMNIRRCGHSENFFFIEVGRSAVTGPGEFWMQV
  DDSVVAQNMHETILEAMRAMSDEFRPRSKSQSSSNCSNPISVPLRRHHLNNPPPSQVGLT
  RRSRTESITATSPASMVGGKPGSFRVRASSDGEGTMSRPASVDGSPVSPSTNRTHAHRHR
  GSARLHPPLNHSRSIPMPASRCSPSATSPVSLSSSSTSGHGSTSDCLFPRRSSASVSGSP
  SDGGFISSDEYGSSPCDFRSSFRSVTPDSLGHTPPARGEEELSNYICMGGKGPSTLTAPN
  GHYILSRGGNGHRCTPGTGLGTSPALAGDEAASAADLDNRFRKRTHSAGTSPTITHQKTP
  SQSSVASIEEYTEMMPAYPPGGGSGGRLPGHRHSAFVPTRSYPEEGLEMHPLERRGGHHR
  PDSSTLHTDDGYMPMSPGVAPVPSGRKGSGDYMPMSPKSVSAPQQIINPIRRHPQRVDPN
  GYMMMSPSGGCSPDIGGGPSSSSSSSNAVPSGTSYGKLWTNGVGGHHSHVLPHPKPPVES
  SGGKLLPCTGDYMNMSPVGDSNTSSPSDCYYGPEDPQHKPVLSYYSLPRSFKHTQRPGEP
  EEGARHQHLRLSTSSGRLLYAATADDSSSSTSSDSLGGGYCGARLEPSLPHPHHQVLQPH
  LPRKVDTAAQTNSRLARPTRLSLGDPKASTLPRAREQQQQQQPLLHPPEPKSPGEYVNIE
  FGSDQSGYLSGPVAFHSSPSVRCPSQLQPAPREEETGTEEYMKMDLGPGRRAAWQESTGV
  EMGRLGPAPPGAASICRPTRAVPSSRGDYMTMQMSCPRQSYVDTSPAAPVSYADMRTGIA
  AEEVSLPRATMAAASSSSAASASPTGPQGAAELAAHSSLLGGPQGPGGMSAFTRVNLSPN
  RNQSAKVIRADPQGCRRRHSSETFSSTPSATRVGNTVPFGAGAAVGGGGGSSSSSEDVKR
  HSSASFENVWLRPGELGGAPKEPAKLCGAAGGLENGLNYIDLDLVKDFKQCPQECTPEPQ
  PPPPPPPHQPLGSGESSSTRRSSEDLSAYASISFQKQPEDRQ
• Function: May mediate the control of various cellular processes by insulin. When phosphorylated by the insulin receptor binds specifically to various cellular proteins containing SH2 domains such as phosphatidylinositol 3-kinase p85 subunit or GRB2. Activates phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit.
• KEGG Pathway:
  cGMP-PKG sig.ling pathway (hsa04022)
  FoxO sig.ling pathway (hsa04068)
  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)
  Neurotrophin sig.ling pathway (hsa04722)
  Insulin sig.ling pathway (hsa04910)
  Adipocytokine sig.ling pathway (hsa04920)
  Regulation of lipolysis in adipocytes (hsa04923)
  Type II diabetes mellitus (hsa04930)
  Insulin resistance (hsa04931)
  Non-alcoholic fatty liver disease (hsa04932)
  Growth hormone synthesis, secretion and action (hsa04935)
  Aldosterone-regulated sodium reabsorption (hsa04960)
  Alzheimer disease (hsa05010)
  MicroR.s in cancer (hsa05206)
  Diabetic cardiomyopathy (hsa05415)
• Reactome Pathway:
  IRS-mediated signalling (R-HSA-112399)
  SOS-mediated signalling (R-HSA-112412)
  PIP3 activates AKT signaling (R-HSA-1257604)
  Interleukin-7 signaling (R-HSA-1266695)
  PI3K/AKT activation (R-HSA-198203)
  Signaling by ALK (R-HSA-201556)
  Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530)
  IRS-related events triggered by IGF1R (R-HSA-2428928)
  Signaling by Leptin (R-HSA-2586552)
  RAF/MAP kinase cascade (R-HSA-5673001)
  PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558)
  IRS activation (R-HSA-74713)
  Signal attenuation (R-HSA-74749)
  Activated NTRK3 signals through PI3K (R-HSA-9603381)
  Signaling by ALK fusions and activated point mutants (R-HSA-9725370)
  Growth hormone receptor signaling (R-HSA-982772)
  PI3K Cascade (R-HSA-109704)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Ethanol	DMDRQZU	Approved	Insulin receptor substrate 1 (IRS1) increases the Liver injury ADR of Ethanol.	[38]
Aspirin	DM672AH	Approved	Insulin receptor substrate 1 (IRS1) affects the response to substance of Aspirin.	[39]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
ANW-32821	DMMJOZD	Phase 2	Insulin receptor substrate 1 (IRS1) affects the abundance of ANW-32821.	[40]

36 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 Insulin receptor substrate 1 (IRS1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Insulin receptor substrate 1 (IRS1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Insulin receptor substrate 1 (IRS1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Insulin receptor substrate 1 (IRS1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Insulin receptor substrate 1 (IRS1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Insulin receptor substrate 1 (IRS1).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Insulin receptor substrate 1 (IRS1).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Insulin receptor substrate 1 (IRS1).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Insulin receptor substrate 1 (IRS1).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Insulin receptor substrate 1 (IRS1).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Insulin receptor substrate 1 (IRS1).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Insulin receptor substrate 1 (IRS1).	[12]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Insulin receptor substrate 1 (IRS1).	[13]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Insulin receptor substrate 1 (IRS1).	[14]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Insulin receptor substrate 1 (IRS1).	[8]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Insulin receptor substrate 1 (IRS1).	[16]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Insulin receptor substrate 1 (IRS1).	[18]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Insulin receptor substrate 1 (IRS1).	[14]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Insulin receptor substrate 1 (IRS1).	[20]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Insulin receptor substrate 1 (IRS1).	[21]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Insulin receptor substrate 1 (IRS1).	[22]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Insulin receptor substrate 1 (IRS1).	[23]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Insulin receptor substrate 1 (IRS1).	[24]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Insulin receptor substrate 1 (IRS1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Insulin receptor substrate 1 (IRS1).	[25]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Insulin receptor substrate 1 (IRS1).	[26]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Insulin receptor substrate 1 (IRS1).	[27]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Insulin receptor substrate 1 (IRS1).	[28]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the expression of Insulin receptor substrate 1 (IRS1).	[30]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Insulin receptor substrate 1 (IRS1).	[31]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Insulin receptor substrate 1 (IRS1).	[32]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Insulin receptor substrate 1 (IRS1).	[33]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Insulin receptor substrate 1 (IRS1).	[34]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the expression of Insulin receptor substrate 1 (IRS1).	[36]
Cycloheximide	DMGDA3C	Investigative	Cycloheximide decreases the expression of Insulin receptor substrate 1 (IRS1).	[8]
Rutin	DMEHRAJ	Investigative	Rutin decreases the expression of Insulin receptor substrate 1 (IRS1).	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Progesterone	DMUY35B	Approved	Progesterone decreases the phosphorylation of Insulin receptor substrate 1 (IRS1).	[15]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the phosphorylation of Insulin receptor substrate 1 (IRS1).	[19]
Methamphetamine	DMPM4SK	Approved	Methamphetamine decreases the phosphorylation of Insulin receptor substrate 1 (IRS1).	[19]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Insulin receptor substrate 1 (IRS1).	[29]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Insulin receptor substrate 1 (IRS1).	[29]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the phosphorylation of Insulin receptor substrate 1 (IRS1).	[35]
Microcystin-LR	DMTMLRN	Investigative	Microcystin-LR increases the phosphorylation of Insulin receptor substrate 1 (IRS1).	[37]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bortezomib	DMNO38U	Approved	Bortezomib decreases the degradation of Insulin receptor substrate 1 (IRS1).	[17]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug decreases the degradation of Insulin receptor substrate 1 (IRS1).	[17]

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