Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ85PDU)

• DOT Name: Insulin (INS)
• Gene Name: INS
• Related Disease:
  Monogenic diabetes
  Diabetes mellitus, permanent neonatal 4
  Hyperproinsulinemia
  Maturity-onset diabetes of the young type 10
  Permanent neonatal diabetes mellitus
  Transient neonatal diabetes mellitus
  Type 1 diabetes mellitus 2
  Maturity-onset diabetes of the young
• UniProt ID: INS_HUMAN
• PDB ID: 1A7F ; 1AI0 ; 1AIY ; 1B9E ; 1BEN ; 1EFE ; 1EV3 ; 1EV6 ; 1EVR ; 1FU2 ; 1FUB ; 1G7A ; 1G7B ; 1GUJ ; 1HIQ ; 1HIS ; 1HIT ; 1HLS ; 1HTV ; 1HUI ; 1IOG ; 1IOH ; 1J73 ; 1JCA ; 1JCO ; 1JK8 ; 1K3M ; 1KMF ; 1LKQ ; 1LPH ; 1MHI ; 1MHJ ; 1MSO ; 1OS3 ; 1OS4 ; 1Q4V ; 1QIY ; 1QIZ ; 1QJ0 ; 1RWE ; 1SF1 ; 1SJT ; 1SJU ; 1T0C ; 1T1K ; 1T1P ; 1T1Q ; 1TRZ ; 1TYL ; 1TYM ; 1UZ9 ; 1VKT ; 1W8P ; 1XDA ; 1XGL ; 1XW7 ; 1ZEG ; 1ZEH ; 1ZNJ ; 2AIY ; 2C8Q ; 2C8R ; 2CEU ; 2G54 ; 2G56 ; 2H67 ; 2HH4 ; 2HHO ; 2HIU ; 2JMN ; 2JUM ; 2JUU ; 2JUV ; 2JV1 ; 2JZQ ; 2K91 ; 2K9R ; 2KJJ ; 2KJU ; 2KQP ; 2KQQ ; 2KXK ; 2L1Y ; 2L1Z ; 2LGB ; 2LWZ ; 2M1D ; 2M1E ; 2M2M ; 2M2N ; 2M2O ; 2M2P ; 2MLI ; 2MPG ; 2MPI ; 2MVC ; 2MVD ; 2N2V ; 2N2W ; 2N2X ; 2OLY ; 2OLZ ; 2OM0 ; 2OM1 ; 2OMG ; 2OMH ; 2OMI ; 2OMQ ; 2QIU ; 2R34 ; 2R35 ; 2R36 ; 2RN5 ; 2VJZ ; 2VK0 ; 2W44 ; 2WBY ; 2WC0 ; 2WRU ; 2WRV ; 2WRW ; 2WRX ; 2WS0 ; 2WS1 ; 2WS4 ; 2WS6 ; 2WS7 ; 3AIY ; 3BXQ ; 3E7Y ; 3E7Z ; 3EXX ; 3FQ9 ; 3HYD ; 3I3Z ; 3I40 ; 3ILG ; 3INC ; 3IR0 ; 3JSD ; 3KQ6 ; 3P2X ; 3P33 ; 3Q6E ; 3ROV ; 3TT8 ; 3U4N ; 3UTQ ; 3UTS ; 3UTT ; 3V19 ; 3V1G ; 3W11 ; 3W12 ; 3W13 ; 3W7Y ; 3W7Z ; 3W80 ; 3ZI3 ; 3ZQR ; 3ZS2 ; 3ZU1 ; 4AIY ; 4AJX ; 4AJZ ; 4AK0 ; 4AKJ ; 4CXL ; 4CXN ; 4CY7 ; 4EFX ; 4EWW ; 4EWX ; 4EWZ ; 4EX0 ; 4EX1 ; 4EXX ; 4EY1 ; 4EY9 ; 4EYD ; 4EYN ; 4EYP ; 4F0N ; 4F0O ; 4F1A ; 4F1B ; 4F1C ; 4F1D ; 4F1F ; 4F1G ; 4F4T ; 4F4V ; 4F51 ; 4F8F ; 4FG3 ; 4FKA ; 4GBC ; 4GBI ; 4GBK ; 4GBL ; 4GBN ; 4IUZ ; 4IYD ; 4IYF ; 4NIB ; 4OGA ; 4P65 ; 4RXW ; 4UNE ; 4UNG ; 4UNH ; 4WDI ; 4XC4 ; 4Y19 ; 4Y1A ; 4Z76 ; 4Z77 ; 4Z78 ; 5AIY ; 5BOQ ; 5BPO ; 5BQQ ; 5BTS ; 5C0D ; 5CJO ; 5CNY ; 5CO2 ; 5CO6 ; 5CO9 ; 5E7W ; 5EMS ; 5EN9 ; 5ENA ; 5HPR ; 5HPU ; 5HQI ; 5HRQ ; 5HYJ ; 5MAM ; 5MHD ; 5MT3 ; 5MT9 ; 5MWQ ; 5T7R ; 5UDP ; 5UOZ ; 5UQA ; 5URT ; 5URU ; 5USP ; 5USS ; 5USV ; 5UU2 ; 5UU3 ; 5UU4 ; 5VIZ ; 5WBT ; 5WDM ; 5WOB ; 6B3Q ; 6B70 ; 6BFC ; 6CE7 ; 6CE9 ; 6CEB ; 6CK2 ; 6GNQ ; 6GV0 ; 6H3M ; 6HN5 ; 6JK8 ; 6JR3 ; 6K59 ; 6NWV ; 6O17 ; 6P4Z ; 6S34 ; 6S4I ; 6S4J ; 6SOF ; 6TC2 ; 6TYH ; 6U46 ; 6VEP ; 6VER ; 6VES ; 6VET ; 6X4X ; 6Z7W ; 6Z7Y ; 7BW7 ; 7BW8 ; 7BWA ; 7JP3 ; 7KD6 ; 7MD4 ; 7MD5 ; 7MQO ; 7MQR ; 7MQS ; 7NHU ; 7NMG ; 7PG0 ; 7PG2 ; 7PG3 ; 7PG4 ; 7QAC ; 7QGF ; 7QID ; 7RKD ; 7RZE ; 7RZF ; 7RZI ; 7S4Y ; 7SL1 ; 7SL2 ; 7SL3 ; 7SL4 ; 7SL6 ; 7SL7 ; 7STH ; 7STI ; 7STJ ; 7STK ; 7U6E ; 7V3P ; 7YQ3 ; 7YQ4 ; 7YQ5 ; 7Z5L ; 7Z5Q ; 8EYX ; 8EYY ; 8EZ0 ; 8GSG ; 8GUY ; 8PI4 ; 8PI5 ; 8PI6 ; 8SBD
• Pfam ID: PF00049
• Sequence:
  MALWMRLLPLLALLALWGPDPAAAFVNQHLCGSHLVEALYLVCGERGFFYTPKTRREAED
  LQVGQVELGGGPGAGSLQPLALEGSLQKRGIVEQCCTSICSLYQLENYCN
• Function: Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver.
• KEGG Pathway:
  MAPK sig.ling pathway (hsa04010)
  Ras sig.ling pathway (hsa04014)
  Rap1 sig.ling pathway (hsa04015)
  cGMP-PKG sig.ling pathway (hsa04022)
  HIF-1 sig.ling pathway (hsa04066)
  FoxO sig.ling pathway (hsa04068)
  Phospholipase D sig.ling pathway (hsa04072)
  Oocyte meiosis (hsa04114)
  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)
  Regulation of actin cytoskeleton (hsa04810)
  Insulin sig.ling pathway (hsa04910)
  Insulin secretion (hsa04911)
  Ovarian steroidogenesis (hsa04913)
  Progesterone-mediated oocyte maturation (hsa04914)
  Prolactin sig.ling pathway (hsa04917)
  Regulation of lipolysis in adipocytes (hsa04923)
  Type II diabetes mellitus (hsa04930)
  Insulin resistance (hsa04931)
  Non-alcoholic fatty liver disease (hsa04932)
  Type I diabetes mellitus (hsa04940)
  Maturity onset diabetes of the young (hsa04950)
  Aldosterone-regulated sodium reabsorption (hsa04960)
  Alzheimer disease (hsa05010)
  Prostate cancer (hsa05215)
  Diabetic cardiomyopathy (hsa05415)
• Reactome Pathway:
  Insulin processing (R-HSA-264876)
  Synthesis, secretion, and deacylation of Ghrelin (R-HSA-422085)
  Regulation of insulin secretion (R-HSA-422356)
  COPI-mediated anterograde transport (R-HSA-6807878)
  PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558)
  IRS activation (R-HSA-74713)
  Signal attenuation (R-HSA-74749)
  Insulin receptor signalling cascade (R-HSA-74751)
  Signaling by Insulin receptor (R-HSA-74752)
  Insulin receptor recycling (R-HSA-77387)
  FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes (R-HSA-9615017)
  NPAS4 regulates expression of target genes (R-HSA-9768919)
  Amyloid fiber formation (R-HSA-977225)
  Regulation of gene expression in beta cells (R-HSA-210745)
• BioCyc Pathway: MetaCyc:MONOMER-16190

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Monogenic diabetes	DISEB8Q0	Definitive	Autosomal recessive	[1]
Diabetes mellitus, permanent neonatal 4	DIS2WS89	Strong	Autosomal dominant	[2]
Hyperproinsulinemia	DISSQ05S	Strong	Autosomal dominant	[2]
Maturity-onset diabetes of the young type 10	DIS5FPQO	Strong	Autosomal dominant	[2]
Permanent neonatal diabetes mellitus	DIS5AEXS	Strong	Autosomal dominant	[2]
Transient neonatal diabetes mellitus	DIST826V	Strong	Autosomal dominant	[2]
Type 1 diabetes mellitus 2	DISAHTZ7	Strong	Autosomal dominant	[2]
Maturity-onset diabetes of the young	DISG75M5	Supportive	Autosomal dominant	[3]

This DOT Affected the Drug Response of 6 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Insulin (INS) increases the response to substance of Quercetin.	[49]
Ethanol	DMDRQZU	Approved	Insulin (INS) increases the Blood insulin abnormal ADR of Ethanol.	[53]
Digoxin	DMQCTIH	Approved	Insulin (INS) decreases the response to substance of Digoxin.	[56]
Triamcinolone	DM98IXF	Approved	Insulin (INS) increases the Malignant melanoma ADR of Triamcinolone.	[53]
Resveratrol	DM3RWXL	Phase 3	Insulin (INS) decreases the response to substance of Resveratrol.	[57]
P-Coumaric Acid	DMGJSVD	Investigative	Insulin (INS) decreases the response to substance of P-Coumaric Acid.	[57]

This DOT Affected the Biotransformations of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydrogen peroxide	DM1NG5W	Approved	Insulin (INS) increases the chemical synthesis of Hydrogen peroxide.	[46]
Hexadecanoic acid	DMWUXDZ	Investigative	Insulin (INS) decreases the oxidation of Hexadecanoic acid.	[59]

This DOT Affected the Regulation of Drug Effects of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Nitric Oxide	DM1RBYG	Approved	Insulin (INS) decreases the secretion of Nitric Oxide.	[54]
2-deoxyglucose	DMIAHVU	Approved	Insulin (INS) increases the uptake of 2-deoxyglucose.	[55]
Milchsaure	DM462BT	Investigative	Insulin (INS) increases the secretion of Milchsaure.	[58]

3 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 (INS).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the methylation of Insulin (INS).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Insulin (INS).	[42]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Insulin (INS).	[5]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Insulin (INS).	[7]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Insulin (INS).	[8]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Insulin (INS).	[10]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Insulin (INS).	[11]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Insulin (INS).	[12]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Insulin (INS).	[14]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of Insulin (INS).	[15]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone increases the expression of Insulin (INS).	[16]
Dopamine	DMPGUCF	Approved	Dopamine increases the expression of Insulin (INS).	[17]
Bezafibrate	DMZDCS0	Approved	Bezafibrate decreases the expression of Insulin (INS).	[18]
Olanzapine	DMPFN6Y	Approved	Olanzapine increases the expression of Insulin (INS).	[19]
Orlistat	DMRJSP8	Approved	Orlistat decreases the expression of Insulin (INS).	[20]
Tacrolimus	DMZ7XNQ	Approved	Tacrolimus decreases the expression of Insulin (INS).	[21]
Propranolol	DM79NTF	Approved	Propranolol decreases the expression of Insulin (INS).	[24]
Epinephrine	DM3KJBC	Approved	Epinephrine decreases the expression of Insulin (INS).	[25]
Carvedilol	DMHTEAO	Approved	Carvedilol decreases the expression of Insulin (INS).	[26]
Salbutamol	DMN9CWF	Approved	Salbutamol increases the expression of Insulin (INS).	[28]
Amlodipine	DMBDAZV	Approved	Amlodipine decreases the expression of Insulin (INS).	[29]
Glibenclamide	DM8JXPZ	Approved	Glibenclamide increases the expression of Insulin (INS).	[30]
Risperidone	DMN6DXL	Approved	Risperidone increases the expression of Insulin (INS).	[19]
Octreotide	DMHIDCJ	Approved	Octreotide decreases the expression of Insulin (INS).	[32]
Bromocriptine	DMVE3TK	Approved	Bromocriptine decreases the expression of Insulin (INS).	[33]
Glimepiride	DM5FSJA	Approved	Glimepiride decreases the expression of Insulin (INS).	[30]
Terbutaline	DMD4381	Approved	Terbutaline increases the expression of Insulin (INS).	[34]
Metoclopramide	DMFA5MY	Approved	Metoclopramide increases the expression of Insulin (INS).	[17]
Sulpiride	DMF54ZG	Approved	Sulpiride increases the expression of Insulin (INS).	[12]
Chlorpropamide	DMPHZQE	Approved	Chlorpropamide increases the expression of Insulin (INS).	[30]
MOXONIDINE	DMGFB0E	Approved	MOXONIDINE decreases the expression of Insulin (INS).	[39]
Atorvastatin	DMF28YC	Phase 3 Trial	Atorvastatin increases the expression of Insulin (INS).	[29]
Telmisartan	DMS3GX2	Phase 3 Trial	Telmisartan decreases the expression of Insulin (INS).	[40]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Insulin (INS).	[43]
AMEP	DMFELMQ	Phase 1	AMEP increases the expression of Insulin (INS).	[44]
Harmine	DMPA5WD	Patented	Harmine increases the expression of Insulin (INS).	[45]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of Insulin (INS).	[44]
D-glucose	DMMG2TO	Investigative	D-glucose increases the activity of Insulin (INS).	[48]
Sucrose	DMVWUCF	Investigative	Sucrose increases the expression of Insulin (INS).	[51]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the response to substance of Insulin (INS).	[9]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the secretion of Insulin (INS).	[13]
Fructose	DM43AN2	Approved	Fructose decreases the response to substance of Insulin (INS).	[22]
Clofibrate	DMPC1J7	Approved	Clofibrate decreases the secretion of Insulin (INS).	[23]
Clonidine	DM6RZ9Q	Approved	Clonidine decreases the secretion of Insulin (INS).	[27]
Methadone	DMTW6IU	Approved	Methadone decreases the response to substance of Insulin (INS).	[31]
Tolbutamide	DM02AWV	Approved	Tolbutamide increases the secretion of Insulin (INS).	[35]
Calcidiol	DMN4CV5	Approved	Calcidiol affects the secretion of Insulin (INS).	[36]
Pentagastrin	DMRCLZB	Approved	Pentagastrin increases the secretion of Insulin (INS).	[37]
Nateglinide	DMLK2QH	Approved	Nateglinide increases the secretion of Insulin (INS).	[38]
BAICALEIN	DM4C7E6	Phase 2	BAICALEIN increases the secretion of Insulin (INS).	[41]
NS398	DMINUWH	Terminated	NS398 increases the secretion of Insulin (INS).	[41]
SKF-96365	DMI79JN	Terminated	SKF-96365 decreases the response to substance of Insulin (INS).	[46]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the secretion of Insulin (INS).	[47]
Arachidonic acid	DMUOQZD	Investigative	Arachidonic acid increases the secretion of Insulin (INS).	[41]
Wogonin	DMGCF51	Investigative	Wogonin increases the response to substance of Insulin (INS).	[49]
DEMETHOXYCURCUMIN	DMO5UGV	Investigative	DEMETHOXYCURCUMIN increases the secretion of Insulin (INS).	[50]
GW-8510	DML4UMT	Investigative	GW-8510 increases the secretion of Insulin (INS).	[52]
1,1,1-trifluoroheptadecan-2-one	DMB5U3P	Investigative	1,1,1-trifluoroheptadecan-2-one increases the secretion of Insulin (INS).	[41]
ARACHIDONYL TRIFLUOROMETHYLKETONE	DMHL48F	Investigative	ARACHIDONYL TRIFLUOROMETHYLKETONE increases the secretion of Insulin (INS).	[41]

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