Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1D416P)

• DOT Name: Insulin-like growth factor-binding protein 7 (IGFBP7)
• Synonyms: IBP-7; IGF-binding protein 7; IGFBP-7; IGFBP-rP1; MAC25 protein; PGI2-stimulating factor; Prostacyclin-stimulating factor; Tumor-derived adhesion factor; TAF
• Gene Name: IGFBP7
• Related Disease: Familial retinal arterial macroaneurysm
• UniProt ID: IBP7_HUMAN
• Pfam ID: PF07679 ; PF00219 ; PF07648
• Sequence:
  MERPSLRALLLGAAGLLLLLLPLSSSSSSDTCGPCEPASCPPLPPLGCLLGETRDACGCC
  PMCARGEGEPCGGGGAGRGYCAPGMECVKSRKRRKGKAGAAAGGPGVSGVCVCKSRYPVC
  GSDGTTYPSGCQLRAASQRAESRGEKAITQVSKGTCEQGPSIVTPPKDIWNVTGAQVYLS
  CEVIGIPTPVLIWNKVKRGHYGVQRTELLPGDRDNLAIQTRGGPEKHEVTGWVLVSPLSK
  EDAGEYECHASNSQGQASASAKITVVDALHEIPVKKGEGAEL
• Function: Binds IGF-I and IGF-II with a relatively low affinity. Stimulates prostacyclin (PGI2) production. Stimulates cell adhesion.
• Reactome Pathway:
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)
  Post-translational protein phosphorylation (R-HSA-8957275)
  Senescence-Associated Secretory Phenotype (SASP) (R-HSA-2559582)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Familial retinal arterial macroaneurysm	DISSZQC9	Strong	Autosomal recessive	[1]

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Insulin-like growth factor-binding protein 7 (IGFBP7) affects the response to substance of Methotrexate.	[30]
Etoposide	DMNH3PG	Approved	Insulin-like growth factor-binding protein 7 (IGFBP7) affects the response to substance of Etoposide.	[30]
Topotecan	DMP6G8T	Approved	Insulin-like growth factor-binding protein 7 (IGFBP7) affects the response to substance of Topotecan.	[30]
Mitoxantrone	DMM39BF	Approved	Insulin-like growth factor-binding protein 7 (IGFBP7) affects the response to substance of Mitoxantrone.	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Insulin-like growth factor-binding protein 7 (IGFBP7).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Insulin-like growth factor-binding protein 7 (IGFBP7).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Insulin-like growth factor-binding protein 7 (IGFBP7).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Insulin-like growth factor-binding protein 7 (IGFBP7).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Insulin-like growth factor-binding protein 7 (IGFBP7).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Insulin-like growth factor-binding protein 7 (IGFBP7).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Insulin-like growth factor-binding protein 7 (IGFBP7).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Insulin-like growth factor-binding protein 7 (IGFBP7).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Insulin-like growth factor-binding protein 7 (IGFBP7).	[10]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Insulin-like growth factor-binding protein 7 (IGFBP7).	[11]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Insulin-like growth factor-binding protein 7 (IGFBP7).	[12]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Insulin-like growth factor-binding protein 7 (IGFBP7).	[13]
Marinol	DM70IK5	Approved	Marinol increases the expression of Insulin-like growth factor-binding protein 7 (IGFBP7).	[14]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Insulin-like growth factor-binding protein 7 (IGFBP7).	[15]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Insulin-like growth factor-binding protein 7 (IGFBP7).	[16]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Insulin-like growth factor-binding protein 7 (IGFBP7).	[17]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Insulin-like growth factor-binding protein 7 (IGFBP7).	[18]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Insulin-like growth factor-binding protein 7 (IGFBP7).	[15]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Insulin-like growth factor-binding protein 7 (IGFBP7).	[19]
Coprexa	DMA0WEK	Phase 3	Coprexa increases the expression of Insulin-like growth factor-binding protein 7 (IGFBP7).	[20]
APR-246	DMNFADH	Phase 2	APR-246 increases the expression of Insulin-like growth factor-binding protein 7 (IGFBP7).	[21]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Insulin-like growth factor-binding protein 7 (IGFBP7).	[22]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Insulin-like growth factor-binding protein 7 (IGFBP7).	[23]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Insulin-like growth factor-binding protein 7 (IGFBP7).	[25]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Insulin-like growth factor-binding protein 7 (IGFBP7).	[26]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Insulin-like growth factor-binding protein 7 (IGFBP7).	[27]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Insulin-like growth factor-binding protein 7 (IGFBP7).	[28]
Arachidonic acid	DMUOQZD	Investigative	Arachidonic acid decreases the expression of Insulin-like growth factor-binding protein 7 (IGFBP7).	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Insulin-like growth factor-binding protein 7 (IGFBP7).	[24]

References

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• [23] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [24] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
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