Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ4O6MW)

• DOT Name: Insulin-like growth factor II (IGF2)
• Synonyms: IGF-II; Somatomedin-A; T3M-11-derived growth factor
• Gene Name: IGF2
• Related Disease:
  Beckwith-Wiedemann syndrome
  Silver-Russell syndrome 1
  Silver-Russell syndrome 3
• UniProt ID: IGF2_HUMAN
• PDB ID: 1IGL; 2L29; 2V5P; 3E4Z; 3KR3; 5L3L; 5L3M; 5L3N; 6UM2; 6VWG; 6VWI
• Pfam ID: PF08365 ; PF00049
• Sequence:
  MGIPMGKSMLVLLTFLAFASCCIAAYRPSETLCGGELVDTLQFVCGDRGFYFSRPASRVS
  RRSRGIVEECCFRSCDLALLETYCATPAKSERDVSTPPTVLPDNFPRYPVGKFFQYDTWK
  QSTQRLRRGLPALLRARRGHVLAKELEAFREAKRHRPLIALPTQDPAHGGAPPEMASNRK
• Function: The insulin-like growth factors possess growth-promoting activity. Major fetal growth hormone in mammals. Plays a key role in regulating fetoplacental development. IGF2 is influenced by placental lactogen. Also involved in tissue differentiation. In adults, involved in glucose metabolism in adipose tissue, skeletal muscle and liver (Probable). Acts as a ligand for integrin which is required for IGF2 signaling. Positively regulates myogenic transcription factor MYOD1 function by facilitating the recruitment of transcriptional coactivators, thereby controlling muscle terminal differentiation. Inhibits myoblast differentiation and modulates metabolism via increasing the mitochondrial respiration rate; Preptin undergoes glucose-mediated co-secretion with insulin, and acts as a physiological amplifier of glucose-mediated insulin secretion. Exhibits osteogenic properties by increasing osteoblast mitogenic activity through phosphoactivation of MAPK1 and MAPK3.
• Tissue Specificity: Expressed in heart, placenta, lung, liver, muscle, kidney, tongue, limb, eye and pancreas.
• KEGG Pathway:
  MAPK sig.ling pathway (hsa04010)
  Ras sig.ling pathway (hsa04014)
  PI3K-Akt sig.ling pathway (hsa04151)
  Pathways in cancer (hsa05200)
  Proteoglycans in cancer (hsa05205)
  Hepatocellular carcinoma (hsa05225)
• Reactome Pathway:
  Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) (R-HSA-2404192)
  IRS-related events triggered by IGF1R (R-HSA-2428928)
  SHC-related events triggered by IGF1R (R-HSA-2428933)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)
  Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Beckwith-Wiedemann syndrome	DISH15GR	Definitive	Autosomal dominant inheritance with maternal imprinting HP:0012275	[1]
Silver-Russell syndrome 1	DIS0Q3YM	Definitive	Autosomal dominant inheritance with maternal imprinting HP:0012275	[2]
Silver-Russell syndrome 3	DIS4Z4HH	Definitive	Autosomal dominant	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Insulin-like growth factor II (IGF2) affects the response to substance of Temozolomide.	[33]
DTI-015	DMXZRW0	Approved	Insulin-like growth factor II (IGF2) affects the response to substance of DTI-015.	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydrocortisone	DMGEMB7	Approved	Insulin-like growth factor II (IGF2) increases the secretion of Hydrocortisone.	[34]

This DOT Affected the Biotransformations of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Estrone	DM5T6US	Approved	Insulin-like growth factor II (IGF2) increases the chemical synthesis of Estrone.	[17]

27 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-like growth factor II (IGF2).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Insulin-like growth factor II (IGF2).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Insulin-like growth factor II (IGF2).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Insulin-like growth factor II (IGF2).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Insulin-like growth factor II (IGF2).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Insulin-like growth factor II (IGF2).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Insulin-like growth factor II (IGF2).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Insulin-like growth factor II (IGF2).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Insulin-like growth factor II (IGF2).	[12]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Insulin-like growth factor II (IGF2).	[13]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Insulin-like growth factor II (IGF2).	[14]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Insulin-like growth factor II (IGF2).	[15]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Insulin-like growth factor II (IGF2).	[12]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Insulin-like growth factor II (IGF2).	[18]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Insulin-like growth factor II (IGF2).	[19]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol increases the expression of Insulin-like growth factor II (IGF2).	[13]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Insulin-like growth factor II (IGF2).	[22]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Insulin-like growth factor II (IGF2).	[23]
Benzylpenicillin	DMS9503	Phase 3	Benzylpenicillin decreases the expression of Insulin-like growth factor II (IGF2).	[24]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Insulin-like growth factor II (IGF2).	[25]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Insulin-like growth factor II (IGF2).	[26]
UNC0379	DMD1E4J	Preclinical	UNC0379 decreases the expression of Insulin-like growth factor II (IGF2).	[27]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Insulin-like growth factor II (IGF2).	[4]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Insulin-like growth factor II (IGF2).	[29]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Insulin-like growth factor II (IGF2).	[30]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the expression of Insulin-like growth factor II (IGF2).	[31]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid decreases the expression of Insulin-like growth factor II (IGF2).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Folic acid	DMEMBJC	Approved	Folic acid affects the methylation of Insulin-like growth factor II (IGF2).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Insulin-like growth factor II (IGF2).	[28]
Lead acetate	DML0GZ2	Investigative	Lead acetate decreases the methylation of Insulin-like growth factor II (IGF2).	[32]
Phthalic Acid	DMF9T64	Investigative	Phthalic Acid decreases the methylation of Insulin-like growth factor II (IGF2).	[28]

10 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 response to substance of Insulin-like growth factor II (IGF2).	[17]
Nifedipine	DMSVOZT	Approved	Nifedipine decreases the response to substance of Insulin-like growth factor II (IGF2).	[20]
Dantrolene	DM1D8XY	Approved	Dantrolene decreases the response to substance of Insulin-like growth factor II (IGF2).	[20]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the secretion of Insulin-like growth factor II (IGF2).	[21]
LY294002	DMY1AFS	Phase 1	LY294002 decreases the response to substance of Insulin-like growth factor II (IGF2).	[17]
MG-132	DMKA2YS	Preclinical	MG-132 decreases the response to substance of Insulin-like growth factor II (IGF2).	[17]
SB 203580	DMAET6F	Terminated	SB 203580 decreases the response to substance of Insulin-like growth factor II (IGF2).	[17]
Wortmannin	DM8EVK5	Terminated	Wortmannin decreases the response to substance of Insulin-like growth factor II (IGF2).	[17]
BAY11-7082	DMQNOFA	Investigative	BAY11-7082 decreases the response to substance of Insulin-like growth factor II (IGF2).	[17]
EGTA	DMW9MRO	Investigative	EGTA decreases the response to substance of Insulin-like growth factor II (IGF2).	[20]

References

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