Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5THARI)

• DOT Name: Apolipoprotein A-I (APOA1)
• Synonyms: Apo-AI; ApoA-I; Apolipoprotein A1
• Gene Name: APOA1
• Related Disease:
  Familial visceral amyloidosis
  Hypoalphalipoproteinemia, primary, 2
  AApoAI amyloidosis
  Obsolete apolipoprotein A-I deficiency
• UniProt ID: APOA1_HUMAN
• PDB ID: 1AV1; 1GW3; 1GW4; 1ODP; 1ODQ; 1ODR; 2MSC; 2MSD; 2MSE; 2N5E; 3K2S; 3R2P; 4V6M; 6CC9; 6CCH; 6CCX; 6CLZ; 6CM1; 6PTS; 6PTW; 6W4E; 6W4F; 7KJR; 7RSC; 7RSE; 8EQS
• Pfam ID: PF01442
• Sequence:
  MKAAVLTLAVLFLTGSQARHFWQQDEPPQSPWDRVKDLATVYVDVLKDSGRDYVSQFEGS
  ALGKQLNLKLLDNWDSVTSTFSKLREQLGPVTQEFWDNLEKETEGLRQEMSKDLEEVKAK
  VQPYLDDFQKKWQEEMELYRQKVEPLRAELQEGARQKLHELQEKLSPLGEEMRDRARAHV
  DALRTHLAPYSDELRQRLAARLEALKENGGARLAEYHAKATEHLSTLSEKAKPALEDLRQ
  GLLPVLESFKVSFLSALEEYTKKLNTQ
• Function: Participates in the reverse transport of cholesterol from tissues to the liver for excretion by promoting cholesterol efflux from tissues and by acting as a cofactor for the lecithin cholesterol acyltransferase (LCAT). As part of the SPAP complex, activates spermatozoa motility.
• Tissue Specificity: Major protein of plasma HDL, also found in chylomicrons. Synthesized in the liver and small intestine. The oxidized form at Met-110 and Met-136 is increased in individuals with increased risk for coronary artery disease, such as in carrier of the eNOSa/b genotype and exposure to cigarette smoking. It is also present in increased levels in aortic lesions relative to native ApoA-I and increased levels are seen with increasing severity of disease.
• KEGG Pathway:
  PPAR sig.ling pathway (hsa03320)
  Fat digestion and absorption (hsa04975)
  Vitamin digestion and absorption (hsa04977)
  Cholesterol metabolism (hsa04979)
  African trypanosomiasis (hsa05143)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  ABC transporters in lipid homeostasis (R-HSA-1369062)
  PPARA activates gene expression (R-HSA-1989781)
  Scavenging of heme from plasma (R-HSA-2168880)
  Scavenging by Class B Receptors (R-HSA-3000471)
  Scavenging by Class A Receptors (R-HSA-3000480)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)
  Defective ABCA1 causes TGD (R-HSA-5682113)
  Post-translational protein phosphorylation (R-HSA-8957275)
  Chylomicron assembly (R-HSA-8963888)
  HDL assembly (R-HSA-8963896)
  Chylomicron remodeling (R-HSA-8963901)
  HDL clearance (R-HSA-8964011)
  HDL remodeling (R-HSA-8964058)
  Heme signaling (R-HSA-9707616)
  Retinoid metabolism and transport (R-HSA-975634)
  Amyloid fiber formation (R-HSA-977225)
  Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Familial visceral amyloidosis	DIS7BVSW	Definitive	Autosomal dominant	[1]
Hypoalphalipoproteinemia, primary, 2	DISUG070	Strong	Autosomal recessive	[2]
AApoAI amyloidosis	DIS74WB1	Supportive	Autosomal dominant	[3]
Obsolete apolipoprotein A-I deficiency	DIS4M8L1	Supportive	Autosomal dominant	[4]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Warfarin	DMJYCVW	Approved	Apolipoprotein A-I (APOA1) affects the response to substance of Warfarin.	[40]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
ANW-32821	DMMJOZD	Phase 2	Apolipoprotein A-I (APOA1) increases the export of ANW-32821.	[41]

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 Apolipoprotein A-I (APOA1).	[5]
Olanzapine	DMPFN6Y	Approved	Olanzapine increases the phosphorylation of Apolipoprotein A-I (APOA1).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Apolipoprotein A-I (APOA1).	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Apolipoprotein A-I (APOA1).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Apolipoprotein A-I (APOA1).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Apolipoprotein A-I (APOA1).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Apolipoprotein A-I (APOA1).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Apolipoprotein A-I (APOA1).	[10]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Apolipoprotein A-I (APOA1).	[11]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Apolipoprotein A-I (APOA1).	[12]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Apolipoprotein A-I (APOA1).	[13]
Fenofibrate	DMFKXDY	Approved	Fenofibrate decreases the expression of Apolipoprotein A-I (APOA1).	[14]
Vitamin C	DMXJ7O8	Approved	Vitamin C decreases the expression of Apolipoprotein A-I (APOA1).	[15]
Ursodeoxycholic acid	DMCUT21	Approved	Ursodeoxycholic acid increases the expression of Apolipoprotein A-I (APOA1).	[16]
Chenodiol	DMQ8JIK	Approved	Chenodiol decreases the expression of Apolipoprotein A-I (APOA1).	[17]
Bezafibrate	DMZDCS0	Approved	Bezafibrate decreases the expression of Apolipoprotein A-I (APOA1).	[14]
Nevirapine	DM6HX9B	Approved	Nevirapine increases the expression of Apolipoprotein A-I (APOA1).	[20]
Nifedipine	DMSVOZT	Approved	Nifedipine increases the expression of Apolipoprotein A-I (APOA1).	[21]
Vitamin B3	DMQVRZH	Approved	Vitamin B3 increases the expression of Apolipoprotein A-I (APOA1).	[23]
Atenolol	DMNKG1Z	Approved	Atenolol decreases the expression of Apolipoprotein A-I (APOA1).	[24]
Clonidine	DM6RZ9Q	Approved	Clonidine decreases the expression of Apolipoprotein A-I (APOA1).	[24]
Gemfibrozil	DMD8Q3J	Approved	Gemfibrozil increases the expression of Apolipoprotein A-I (APOA1).	[23]
Ciprofibrate	DMGC5DB	Approved	Ciprofibrate decreases the expression of Apolipoprotein A-I (APOA1).	[14]
Cyproterone acetate	DMLMOIJ	Phase 4	Cyproterone acetate affects the expression of Apolipoprotein A-I (APOA1).	[25]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Apolipoprotein A-I (APOA1).	[15]
NCX-4016	DMOX1CU	Phase 2	NCX-4016 increases the expression of Apolipoprotein A-I (APOA1).	[11]
Taurocholic acid	DM2LZ8F	Phase 1/2	Taurocholic acid decreases the expression of Apolipoprotein A-I (APOA1).	[17]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Apolipoprotein A-I (APOA1).	[28]
GSK525762	DMPAWBN	Phase 1	GSK525762 increases the expression of Apolipoprotein A-I (APOA1).	[29]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Apolipoprotein A-I (APOA1).	[30]
CHIR-99021	DMB8MNU	Patented	CHIR-99021 increases the expression of Apolipoprotein A-I (APOA1).	[31]
MK-886	DMT0O7H	Discontinued in Phase 2	MK-886 decreases the expression of Apolipoprotein A-I (APOA1).	[32]
PIRINIXIC ACID	DM82Y75	Preclinical	PIRINIXIC ACID decreases the expression of Apolipoprotein A-I (APOA1).	[14]
Taxifolin	DMQJSF9	Preclinical	Taxifolin increases the expression of Apolipoprotein A-I (APOA1).	[33]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Apolipoprotein A-I (APOA1).	[34]
Arachidonic acid	DMUOQZD	Investigative	Arachidonic acid decreases the expression of Apolipoprotein A-I (APOA1).	[14]
Linalool	DMGZQ5P	Investigative	Linalool increases the expression of Apolipoprotein A-I (APOA1).	[37]
GW7647	DM9RD0C	Investigative	GW7647 increases the expression of Apolipoprotein A-I (APOA1).	[38]
T0901317	DMZQVDI	Investigative	T0901317 decreases the expression of Apolipoprotein A-I (APOA1).	[32]
	DMQNVR8		increases the expression of Apolipoprotein A-I (APOA1).	[39]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Glucosamine	DM4ZLFD	Approved	Glucosamine increases the stability of Apolipoprotein A-I (APOA1).	[19]
Clofibrate	DMPC1J7	Approved	Clofibrate increases the secretion of Apolipoprotein A-I (APOA1).	[22]
Contigoside B	DMX9V8K	Phase 2/3	Contigoside B increases the secretion of Apolipoprotein A-I (APOA1).	[26]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal affects the binding of Apolipoprotein A-I (APOA1).	[35]

1 Drug(s) Affected the Biochemical Pathways of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
acrolein	DMAMCSR	Investigative	acrolein affects the metabolism of Apolipoprotein A-I (APOA1).	[36]

References

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