Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTACYW9J)

• DOT Name: Alpha-1-antitrypsin (SERPINA1)
• Synonyms: Alpha-1 protease inhibitor; Alpha-1-antiproteinase; Serpin A1
• Gene Name: SERPINA1
• Related Disease:
  Alpha-1 antitrypsin deficiency
  Hemorrhagic disease due to alpha-1-antitrypsin Pittsburgh mutation
• UniProt ID: A1AT_HUMAN
• PDB ID: 1ATU ; 1D5S ; 1EZX ; 1HP7 ; 1IZ2 ; 1KCT ; 1OO8 ; 1OPH ; 1PSI ; 1QLP ; 1QMB ; 2D26 ; 2QUG ; 3CWL ; 3CWM ; 3DRM ; 3DRU ; 3NDD ; 3NDF ; 3NE4 ; 3T1P ; 4PYW ; 5IO1 ; 5NBU ; 5NBV ; 6HX4 ; 6I4V ; 6I7U ; 6IAY ; 6ROD ; 7AEL ; 7API ; 7NPK ; 7NPL ; 8API ; 8PI2 ; 9API
• Pfam ID: PF00079
• Sequence:
  MPSSVSWGILLLAGLCCLVPVSLAEDPQGDAAQKTDTSHHDQDHPTFNKITPNLAEFAFS
  LYRQLAHQSNSTNIFFSPVSIATAFAMLSLGTKADTHDEILEGLNFNLTEIPEAQIHEGF
  QELLRTLNQPDSQLQLTTGNGLFLSEGLKLVDKFLEDVKKLYHSEAFTVNFGDTEEAKKQ
  INDYVEKGTQGKIVDLVKELDRDTVFALVNYIFFKGKWERPFEVKDTEEEDFHVDQVTTV
  KVPMMKRLGMFNIQHCKKLSSWVLLMKYLGNATAIFFLPDEGKLQHLENELTHDIITKFL
  ENEDRRSASLHLPKLSITGTYDLKSVLGQLGITKVFSNGADLSGVTEEAPLKLSKAVHKA
  VLTIDEKGTEAAGAMFLEAIPMSIPPEVKFNKPFVFLMIEQNTKSPLFMGKVVNPTQK
• Function: Inhibitor of serine proteases. Its primary target is elastase, but it also has a moderate affinity for plasmin and thrombin. Irreversibly inhibits trypsin, chymotrypsin and plasminogen activator. The aberrant form inhibits insulin-induced NO synthesis in platelets, decreases coagulation time and has proteolytic activity against insulin and plasmin.; [Short peptide from AAT]: Reversible chymotrypsin inhibitor. It also inhibits elastase, but not trypsin. Its major physiological function is the protection of the lower respiratory tract against proteolytic destruction by human leukocyte elastase (HLE).
• Tissue Specificity: Ubiquitous. Expressed in leukocytes and plasma.
• KEGG Pathway: Complement and coagulation cascades (hsa04610)
• Reactome Pathway:
  COPII-mediated vesicle transport (R-HSA-204005)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)
  Cargo concentration in the ER (R-HSA-5694530)
  Neutrophil degranulation (R-HSA-6798695)
  Post-translational protein phosphorylation (R-HSA-8957275)
  Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alpha-1 antitrypsin deficiency	DISQKEHW	Strong	Autosomal recessive	[1]
Hemorrhagic disease due to alpha-1-antitrypsin Pittsburgh mutation	DIS7BDKO	Supportive	Autosomal dominant	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Indomethacin	DMSC4A7	Approved	Alpha-1-antitrypsin (SERPINA1) increases the response to substance of Indomethacin.	[28]
PMID28870136-Compound-48	DMPIM9L	Patented	Alpha-1-antitrypsin (SERPINA1) affects the response to substance of PMID28870136-Compound-48.	[29]

26 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 Alpha-1-antitrypsin (SERPINA1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Alpha-1-antitrypsin (SERPINA1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Alpha-1-antitrypsin (SERPINA1).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Alpha-1-antitrypsin (SERPINA1).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Alpha-1-antitrypsin (SERPINA1).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Alpha-1-antitrypsin (SERPINA1).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Alpha-1-antitrypsin (SERPINA1).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Alpha-1-antitrypsin (SERPINA1).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Alpha-1-antitrypsin (SERPINA1).	[11]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Alpha-1-antitrypsin (SERPINA1).	[12]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Alpha-1-antitrypsin (SERPINA1).	[13]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Alpha-1-antitrypsin (SERPINA1).	[14]
Folic acid	DMEMBJC	Approved	Folic acid affects the expression of Alpha-1-antitrypsin (SERPINA1).	[15]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Alpha-1-antitrypsin (SERPINA1).	[16]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Alpha-1-antitrypsin (SERPINA1).	[12]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Alpha-1-antitrypsin (SERPINA1).	[17]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Alpha-1-antitrypsin (SERPINA1).	[18]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Alpha-1-antitrypsin (SERPINA1).	[19]
Nabiximols	DMHKJ5I	Phase 3	Nabiximols decreases the expression of Alpha-1-antitrypsin (SERPINA1).	[20]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Alpha-1-antitrypsin (SERPINA1).	[21]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Alpha-1-antitrypsin (SERPINA1).	[18]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Alpha-1-antitrypsin (SERPINA1).	[22]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the expression of Alpha-1-antitrypsin (SERPINA1).	[21]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Alpha-1-antitrypsin (SERPINA1).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Alpha-1-antitrypsin (SERPINA1).	[25]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Alpha-1-antitrypsin (SERPINA1).	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Alpha-1-antitrypsin (SERPINA1).	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug affects the localization of Alpha-1-antitrypsin (SERPINA1).	[27]

References

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