Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD0Z2XO)

• DOT Name: Serum paraoxonase/arylesterase 1 (PON1)
• Synonyms: PON 1; EC 3.1.1.2; EC 3.1.1.81; EC 3.1.8.1; Aromatic esterase 1; A-esterase 1; K-45; Serum aryldialkylphosphatase 1
• Gene Name: PON1
• Related Disease: Amyotrophic lateral sclerosis
• UniProt ID: PON1_HUMAN
• PDB ID: 1V04
• EC Number: 3.1.1.2; 3.1.1.81; 3.1.8.1
• Pfam ID: PF01731
• Sequence:
  MAKLIALTLLGMGLALFRNHQSSYQTRLNALREVQPVELPNCNLVKGIETGSEDLEILPN
  GLAFISSGLKYPGIKSFNPNSPGKILLMDLNEEDPTVLELGITGSKFDVSSFNPHGISTF
  TDEDNAMYLLVVNHPDAKSTVELFKFQEEEKSLLHLKTIRHKLLPNLNDIVAVGPEHFYG
  TNDHYFLDPYLQSWEMYLGLAWSYVVYYSPSEVRVVAEGFDFANGINISPDGKYVYIAEL
  LAHKIHVYEKHANWTLTPLKSLDFNTLVDNISVDPETGDLWVGCHPNGMKIFFYDSENPP
  ASEVLRIQNILTEEPKVTQVYAENGTVLQGSTVASVYKGKLLIGTVFHKALYCEL
• Function: Hydrolyzes the toxic metabolites of a variety of organophosphorus insecticides. Capable of hydrolyzing a broad spectrum of organophosphate substrates and lactones, and a number of aromatic carboxylic acid esters. Mediates an enzymatic protection of low density lipoproteins against oxidative modification and the consequent series of events leading to atheroma formation.
• Tissue Specificity: Plasma, associated with HDL (at protein level). Expressed in liver, but not in heart, brain, placenta, lung, skeletal muscle, kidney or pancreas.
• Reactome Pathway:
  Atorvastatin ADME (R-HSA-9754706)
  Synthesis of 5-eicosatetraenoic acids (R-HSA-2142688)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Amyotrophic lateral sclerosis	DISF7HVM	Supportive	Autosomal dominant	[1]

This DOT Affected the Drug Response of 5 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Serum paraoxonase/arylesterase 1 (PON1) affects the response to substance of Arsenic.	[32]
Clopidogrel	DMOL54H	Approved	Serum paraoxonase/arylesterase 1 (PON1) affects the response to substance of Clopidogrel.	[34]
Chlorpyrifos	DMKPUI6	Investigative	Serum paraoxonase/arylesterase 1 (PON1) increases the response to substance of Chlorpyrifos.	[39]
Aminohippuric acid	DMUN54G	Investigative	Serum paraoxonase/arylesterase 1 (PON1) increases the response to substance of Aminohippuric acid.	[40]
Chlorphrifos oxon	DMGBT68	Investigative	Serum paraoxonase/arylesterase 1 (PON1) decreases the response to substance of Chlorphrifos oxon.	[42]

This DOT Affected the Regulation of Drug Effects of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Eicosapentaenoic acid/docosa-hexaenoic acid	DMMUCG4	Approved	Serum paraoxonase/arylesterase 1 (PON1) affects the metabolism of Eicosapentaenoic acid/docosa-hexaenoic acid.	[33]
Uric acid	DMA1MKT	Investigative	Serum paraoxonase/arylesterase 1 (PON1) affects the abundance of Uric acid.	[41]

This DOT Affected the Biotransformations of 6 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Isoflurophate	DMBSK7X	Approved	Serum paraoxonase/arylesterase 1 (PON1) increases the hydrolysis of Isoflurophate.	[35]
Phenylacetic acid	DMQ95GE	Approved	Serum paraoxonase/arylesterase 1 (PON1) decreases the hydrolysis of Phenylacetic acid.	[36]
ANW-32821	DMMJOZD	Phase 2	Serum paraoxonase/arylesterase 1 (PON1) decreases the chemical synthesis of ANW-32821.	[37]
RTR-003632	DM45NHF	Phase 2	Serum paraoxonase/arylesterase 1 (PON1) increases the hydrolysis of RTR-003632.	[38]
Mononitrophenol	DM4QO9G	Investigative	Serum paraoxonase/arylesterase 1 (PON1) increases the chemical synthesis of Mononitrophenol.	[43]
Nitrophenyl acetate	DMHSD8A	Investigative	Serum paraoxonase/arylesterase 1 (PON1) increases the hydrolysis of Nitrophenyl acetate.	[44]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Serum paraoxonase/arylesterase 1 (PON1).	[2]

52 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 Serum paraoxonase/arylesterase 1 (PON1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Serum paraoxonase/arylesterase 1 (PON1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Serum paraoxonase/arylesterase 1 (PON1).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Serum paraoxonase/arylesterase 1 (PON1).	[3]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Serum paraoxonase/arylesterase 1 (PON1).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the activity of Serum paraoxonase/arylesterase 1 (PON1).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Serum paraoxonase/arylesterase 1 (PON1).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine decreases the activity of Serum paraoxonase/arylesterase 1 (PON1).	[9]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Serum paraoxonase/arylesterase 1 (PON1).	[10]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Serum paraoxonase/arylesterase 1 (PON1).	[8]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Serum paraoxonase/arylesterase 1 (PON1).	[11]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Serum paraoxonase/arylesterase 1 (PON1).	[12]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Serum paraoxonase/arylesterase 1 (PON1).	[13]
Nicotine	DMWX5CO	Approved	Nicotine decreases the activity of Serum paraoxonase/arylesterase 1 (PON1).	[14]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Serum paraoxonase/arylesterase 1 (PON1).	[15]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Serum paraoxonase/arylesterase 1 (PON1).	[16]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of Serum paraoxonase/arylesterase 1 (PON1).	[11]
Phenytoin	DMNOKBV	Approved	Phenytoin affects the activity of Serum paraoxonase/arylesterase 1 (PON1).	[9]
Vitamin C	DMXJ7O8	Approved	Vitamin C decreases the activity of Serum paraoxonase/arylesterase 1 (PON1).	[17]
Chenodiol	DMQ8JIK	Approved	Chenodiol decreases the expression of Serum paraoxonase/arylesterase 1 (PON1).	[18]
Ampicillin	DMHWE7P	Approved	Ampicillin decreases the activity of Serum paraoxonase/arylesterase 1 (PON1).	[19]
Bosentan	DMIOGBU	Approved	Bosentan decreases the expression of Serum paraoxonase/arylesterase 1 (PON1).	[20]
Orlistat	DMRJSP8	Approved	Orlistat increases the activity of Serum paraoxonase/arylesterase 1 (PON1).	[21]
Ciprofloxacin XR	DM2NLS9	Approved	Ciprofloxacin XR decreases the activity of Serum paraoxonase/arylesterase 1 (PON1).	[19]
Methimazole	DM25FL8	Approved	Methimazole increases the activity of Serum paraoxonase/arylesterase 1 (PON1).	[22]
Salbutamol	DMN9CWF	Approved	Salbutamol decreases the activity of Serum paraoxonase/arylesterase 1 (PON1).	[23]
Gabapentin	DM6T924	Approved	Gabapentin decreases the activity of Serum paraoxonase/arylesterase 1 (PON1).	[9]
Fluticasone propionate	DMRWLB2	Approved	Fluticasone propionate decreases the activity of Serum paraoxonase/arylesterase 1 (PON1).	[23]
Pitavastatin	DMJH792	Approved	Pitavastatin increases the expression of Serum paraoxonase/arylesterase 1 (PON1).	[24]
Primidone	DM0WX6I	Approved	Primidone decreases the activity of Serum paraoxonase/arylesterase 1 (PON1).	[9]
Levetiracetam	DMTGDN8	Approved	Levetiracetam affects the activity of Serum paraoxonase/arylesterase 1 (PON1).	[9]
Sulfisoxazole	DMXLT8C	Approved	Sulfisoxazole decreases the activity of Serum paraoxonase/arylesterase 1 (PON1).	[25]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Serum paraoxonase/arylesterase 1 (PON1).	[26]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Serum paraoxonase/arylesterase 1 (PON1).	[27]
Atorvastatin	DMF28YC	Phase 3 Trial	Atorvastatin increases the expression of Serum paraoxonase/arylesterase 1 (PON1).	[24]
NCX-4016	DMOX1CU	Phase 2	NCX-4016 increases the expression of Serum paraoxonase/arylesterase 1 (PON1).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Serum paraoxonase/arylesterase 1 (PON1).	[3]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 decreases the activity of Serum paraoxonase/arylesterase 1 (PON1).	[23]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Serum paraoxonase/arylesterase 1 (PON1).	[28]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the activity of Serum paraoxonase/arylesterase 1 (PON1).	[29]
Arachidonic acid	DMUOQZD	Investigative	Arachidonic acid decreases the activity of Serum paraoxonase/arylesterase 1 (PON1).	[29]
Oleic acid	DM54O1Z	Investigative	Oleic acid decreases the activity of Serum paraoxonase/arylesterase 1 (PON1).	[29]
Paraoxon	DMN4ZKC	Investigative	Paraoxon increases the activity of Serum paraoxonase/arylesterase 1 (PON1).	[13]
Linoleic acid	DMDGPY9	Investigative	Linoleic acid decreases the activity of Serum paraoxonase/arylesterase 1 (PON1).	[7]
methylglyoxal	DMRC3OZ	Investigative	methylglyoxal decreases the activity of Serum paraoxonase/arylesterase 1 (PON1).	[29]
Flavone	DMEQH6J	Investigative	Flavone increases the expression of Serum paraoxonase/arylesterase 1 (PON1).	[6]
ISORHAMNETIN	DMQ4Z6E	Investigative	ISORHAMNETIN increases the expression of Serum paraoxonase/arylesterase 1 (PON1).	[30]
	DM1FBZ7		decreases the activity of Serum paraoxonase/arylesterase 1 (PON1).	[23]
EGTA	DMW9MRO	Investigative	EGTA decreases the activity of Serum paraoxonase/arylesterase 1 (PON1).	[31]
Palmitoleic Acid	DM4W5X8	Investigative	Palmitoleic Acid decreases the activity of Serum paraoxonase/arylesterase 1 (PON1).	[29]
lysophosphatidylinositol	DMETM3R	Investigative	lysophosphatidylinositol decreases the activity of Serum paraoxonase/arylesterase 1 (PON1).	[29]
4-(Hydroxymercury)Benzoic Acid	DMWJN73	Investigative	4-(Hydroxymercury)Benzoic Acid decreases the activity of Serum paraoxonase/arylesterase 1 (PON1).	[7]

References

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