Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT46MJBE)

• DOT Name: Insulin receptor substrate 2 (IRS2)
• Synonyms: IRS-2
• Gene Name: IRS2
• UniProt ID: IRS2_HUMAN
• PDB ID: 3FQW; 3FQX
• Pfam ID: PF02174 ; PF00169
• Sequence:
  MASPPRHGPPGPASGDGPNLNNNNNNNNHSVRKCGYLRKQKHGHKRFFVLRGPGAGGDEA
  TAGGGSAPQPPRLEYYESEKKWRSKAGAPKRVIALDCCLNINKRADAKHKYLIALYTKDE
  YFAVAAENEQEQEGWYRALTDLVSEGRAAAGDAPPAAAPAASCSASLPGALGGSAGAAGA
  EDSYGLVAPATAAYREVWQVNLKPKGLGQSKNLTGVYRLCLSARTIGFVKLNCEQPSVTL
  QLMNIRRCGHSDSFFFIEVGRSAVTGPGELWMQADDSVVAQNIHETILEAMKALKELFEF
  RPRSKSQSSGSSATHPISVPGARRHHHLVNLPPSQTGLVRRSRTDSLAATPPAAKCSSCR
  VRTASEGDGGAAAGAAAAGARPVSVAGSPLSPGPVRAPLSRSHTLSGGCGGRGSKVALLP
  AGGALQHSRSMSMPVAHSPPAATSPGSLSSSSGHGSGSYPPPPGPHPPLPHPLHHGPGQR
  PSSGSASASGSPSDPGFMSLDEYGSSPGDLRAFCSHRSNTPESIAETPPARDGGGGGEFY
  GYMTMDRPLSHCGRSYRRVSGDAAQDLDRGLRKRTYSLTTPARQRPVPQPSSASLDEYTL
  MRATFSGSAGRLCPSCPASSPKVAYHPYPEDYGDIEIGSHRSSSSNLGADDGYMPMTPGA
  ALAGSGSGSCRSDDYMPMSPASVSAPKQILQPRAAAAAAAAVPSAGPAGPAPTSAAGRTF
  PASGGGYKASSPAESSPEDSGYMRMWCGSKLSMEHADGKLLPNGDYLNVSPSDAVTTGTP
  PDFFSAALHPGGEPLRGVPGCCYSSLPRSYKAPYTCGGDSDQYVLMSSPVGRILEEERLE
  PQATPGPSQAASAFGAGPTQPPHPVVPSPVRPSGGRPEGFLGQRGRAVRPTRLSLEGLPS
  LPSMHEYPLPPEPKSPGEYINIDFGEPGARLSPPAPPLLASAASSSSLLSASSPASSLGS
  GTPGTSSDSRQRSPLSDYMNLDFSSPKSPKPGAPSGHPVGSLDGLLSPEASSPYPPLPPR
  PSASPSSSLQPPPPPPAPGELYRLPPASAVATAQGPGAASSLSSDTGDNGDYTEMAFGVA
  ATPPQPIAAPPKPEAARVASPTSGVKRLSLMEQVSGVEAFLQASQPPDPHRGAKVIRADP
  QGGRRRHSSETFSSTTTVTPVSPSFAHNPKRHNSASVENVSLRKSSEGGVGVGPGGGDEP
  PTSPRQLQPAPPLAPQGRPWTPGQPGGLVGCPGSGGSPMRRETSAGFQNGLNYIAIDVRE
  EPGLPPQPQPPPPPLPQPGDKSSWGRTRSLGGLISAVGVGSTGGGCGGPGPGALPPANTY
  ASIDFLSHHLKEATIVKE
• Function: May mediate the control of various cellular processes by insulin.
• KEGG Pathway:
  cGMP-PKG sig.ling pathway (hsa04022)
  FoxO sig.ling pathway (hsa04068)
  Autophagy - animal (hsa04140)
  AMPK sig.ling pathway (hsa04152)
  Longevity regulating pathway (hsa04211)
  Longevity regulating pathway - multiple species (hsa04213)
  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)
  Alzheimer disease (hsa05010)
  MicroR.s in cancer (hsa05206)
• 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)
  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)
  RET signaling (R-HSA-8853659)
  Signaling by Erythropoietin (R-HSA-9006335)
  Erythropoietin activates Phosphoinositide-3-kinase (PI3K) (R-HSA-9027276)
  Erythropoietin activates Phospholipase C gamma (PLCG) (R-HSA-9027277)
  Erythropoietin activates STAT5 (R-HSA-9027283)
  Erythropoietin activates RAS (R-HSA-9027284)
  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 2 (IRS2) increases the Liver injury ADR of Ethanol.	[30]
Etoposide	DMNH3PG	Approved	Insulin receptor substrate 2 (IRS2) affects the response to substance of Etoposide.	[31]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Insulin receptor substrate 2 (IRS2).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Insulin receptor substrate 2 (IRS2).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Insulin receptor substrate 2 (IRS2).	[24]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Insulin receptor substrate 2 (IRS2).	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Insulin receptor substrate 2 (IRS2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Insulin receptor substrate 2 (IRS2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Insulin receptor substrate 2 (IRS2).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Insulin receptor substrate 2 (IRS2).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Insulin receptor substrate 2 (IRS2).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Insulin receptor substrate 2 (IRS2).	[7]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Insulin receptor substrate 2 (IRS2).	[8]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Insulin receptor substrate 2 (IRS2).	[9]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Insulin receptor substrate 2 (IRS2).	[10]
Marinol	DM70IK5	Approved	Marinol increases the expression of Insulin receptor substrate 2 (IRS2).	[11]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Insulin receptor substrate 2 (IRS2).	[12]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Insulin receptor substrate 2 (IRS2).	[13]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Insulin receptor substrate 2 (IRS2).	[14]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Insulin receptor substrate 2 (IRS2).	[15]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Insulin receptor substrate 2 (IRS2).	[16]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Insulin receptor substrate 2 (IRS2).	[17]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Insulin receptor substrate 2 (IRS2).	[18]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Insulin receptor substrate 2 (IRS2).	[19]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Insulin receptor substrate 2 (IRS2).	[20]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Insulin receptor substrate 2 (IRS2).	[22]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Insulin receptor substrate 2 (IRS2).	[23]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Insulin receptor substrate 2 (IRS2).	[25]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Insulin receptor substrate 2 (IRS2).	[26]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Insulin receptor substrate 2 (IRS2).	[27]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Insulin receptor substrate 2 (IRS2).	[7]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the expression of Insulin receptor substrate 2 (IRS2).	[29]

References

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