Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5Z8ERW)

• DOT Name: Islet amyloid polypeptide (IAPP)
• Synonyms: Amylin; Diabetes-associated peptide; DAP; Insulinoma amyloid peptide
• Gene Name: IAPP
• UniProt ID: IAPP_HUMAN
• PDB ID: 1KUW ; 2G48 ; 2KB8 ; 2L86 ; 3DG1 ; 3FPO ; 3FR1 ; 3FTH ; 3FTK ; 3FTL ; 3FTR ; 3G7V ; 3G7W ; 3HGZ ; 5K5G ; 5KNZ ; 5KO0 ; 5MGQ ; 6UCJ ; 6UCK ; 6VW2 ; 6Y1A ; 6ZRF ; 6ZRQ ; 6ZRR ; 7BG0 ; 7M61 ; 7M62 ; 7M64 ; 7M65 ; 7YKW ; 7YL0 ; 7YL3 ; 7YL7 ; 8F0J ; 8F0K ; 8F2A ; 8F2B
• Pfam ID: PF00214
• Sequence:
  MGILKLQVFLIVLSVALNHLKATPIESHQVEKRKCNTATCATQRLANFLVHSSNNFGAIL
  SSTNVGSNTYGKRNAVEVLKREPLNYLPL
• Function: Selectively inhibits insulin-stimulated glucose utilization and glycogen deposition in muscle, while not affecting adipocyte glucose metabolism.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Maturity onset diabetes of the young (hsa04950)
• Reactome Pathway:
  G alpha (s) signalling events (R-HSA-418555)
  Calcitonin-like ligand receptors (R-HSA-419812)
  Amyloid fiber formation (R-HSA-977225)
  Regulation of gene expression in beta cells (R-HSA-210745)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydrogen peroxide	DM1NG5W	Approved	Islet amyloid polypeptide (IAPP) decreases the abundance of Hydrogen peroxide.	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Dexamethasone	DMMWZET	Approved	Islet amyloid polypeptide (IAPP) increases the Investigations ADR of Dexamethasone.	[6]
Insulin	DMB7CE0	Approved	Islet amyloid polypeptide (IAPP) increases the Hypoglycaemia ADR of Insulin.	[6]

3 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 Islet amyloid polypeptide (IAPP).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin affects the expression of Islet amyloid polypeptide (IAPP).	[2]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Islet amyloid polypeptide (IAPP).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Islet amyloid polypeptide (IAPP).	[3]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Molecular characterization of a toxicological tipping point during human stem cell differentiation. Reprod Toxicol. 2020 Jan;91:1-13. doi: 10.1016/j.reprotox.2019.10.001. Epub 2019 Oct 7.
• [3] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [4] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [5] Copper(II)-human amylin complex protects pancreatic cells from amylin toxicity. Phys Chem Chem Phys. 2013 Aug 14;15(30):12558-71. doi: 10.1039/c3cp44542a.
• [6] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.