Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOH3WQ9)

• DOT Name: Cholinesterase (BCHE)
• Synonyms: EC 3.1.1.8; Acylcholine acylhydrolase; Butyrylcholine esterase; Choline esterase II; Pseudocholinesterase
• Gene Name: BCHE
• Related Disease: Butyrylcholinesterase deficiency
• UniProt ID: CHLE_HUMAN
• PDB ID: 1P0I ; 1P0M ; 1P0P ; 1P0Q ; 1XLU ; 1XLV ; 1XLW ; 2J4C ; 2PM8 ; 2WID ; 2WIF ; 2WIG ; 2WIJ ; 2WIK ; 2WIL ; 2WSL ; 2XMB ; 2XMC ; 2XMD ; 2XMG ; 2XQF ; 2XQG ; 2XQI ; 2XQJ ; 2XQK ; 2Y1K ; 3DJY ; 3DKK ; 3O9M ; 4AQD ; 4AXB ; 4B0O ; 4B0P ; 4BBZ ; 4BDS ; 4TPK ; 4XII ; 5DYT ; 5DYW ; 5DYY ; 5K5E ; 5LKR ; 5NN0 ; 6EMI ; 6EP4 ; 6EQP ; 6EQQ ; 6ESJ ; 6ESY ; 6EYF ; 6EZ2 ; 6F7Q ; 6I0B ; 6I0C ; 6I2T ; 6QAA ; 6QAB ; 6QAC ; 6QAD ; 6QAE ; 6R6V ; 6R6W ; 6RUA ; 6SAM ; 6T9P ; 6T9S ; 6XTA ; 6ZWI ; 7AIY ; 7AMZ ; 7AWG ; 7AWH ; 7AWI ; 7BGC ; 7BO3 ; 7BO4 ; 7Q1M ; 7Q1N ; 7Q1O ; 7Q1P ; 7QBQ ; 7QBR ; 7QHD ; 7QHE ; 7ZPB ; 8AI7 ; 8AM1 ; 8AM2 ; 8CGO
• EC Number: 3.1.1.8
• Pfam ID: PF08674 ; PF00135
• Sequence:
  MHSKVTIICIRFLFWFLLLCMLIGKSHTEDDIIIATKNGKVRGMNLTVFGGTVTAFLGIP
  YAQPPLGRLRFKKPQSLTKWSDIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDC
  LYLNVWIPAPKPKNATVLIWIYGGGFQTGTSSLHVYDGKFLARVERVIVVSMNYRVGALG
  FLALPGNPEAPGNMGLFDQQLALQWVQKNIAAFGGNPKSVTLFGESAGAASVSLHLLSPG
  SHSLFTRAILQSGSFNAPWAVTSLYEARNRTLNLAKLTGCSRENETEIIKCLRNKDPQEI
  LLNEAFVVPYGTPLSVNFGPTVDGDFLTDMPDILLELGQFKKTQILVGVNKDEGTAFLVY
  GAPGFSKDNNSIITRKEFQEGLKIFFPGVSEFGKESILFHYTDWVDDQRPENYREALGDV
  VGDYNFICPALEFTKKFSEWGNNAFFYYFEHRSSKLPWPEWMGVMHGYEIEFVFGLPLER
  RDNYTKAEEILSRSIVKRWANFAKYGNPNETQNNSTSWPVFKSTEQKYLTLNTESTRIMT
  KLRAQQCRFWTSFFPKVLEMTGNIDEAEWEWKAGFHRWNNYMMDWKNQFNDYTSKKESCV
  GL
• Function: Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
• Tissue Specificity: Detected in blood plasma (at protein level). Present in most cells except erythrocytes.
• Reactome Pathway:
  Synthesis of PC (R-HSA-1483191)
  Synthesis, secretion, and deacylation of Ghrelin (R-HSA-422085)
  Aspirin ADME (R-HSA-9749641)
  Neurotransmitter clearance (R-HSA-112311)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Butyrylcholinesterase deficiency	DISMQ1JE	Definitive	Autosomal recessive	[1]

This DOT Affected the Biotransformations of 6 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cocaine	DMSOX7I	Approved	Cholinesterase (BCHE) increases the hydrolysis of Cocaine.	[39]
Morphine	DMRMS0L	Approved	Cholinesterase (BCHE) increases the chemical synthesis of Morphine.	[40]
Benzoic acid	DMKB9FI	Approved	Cholinesterase (BCHE) increases the chemical synthesis of Benzoic acid.	[40]
Remdesivir	DMBFZ6L	Phase 3 Trial	Cholinesterase (BCHE) increases the hydrolysis of Remdesivir.	[47]
RTR-003632	DM45NHF	Phase 2	Cholinesterase (BCHE) increases the hydrolysis of RTR-003632.	[48]
Butyrylthiocholine	DMOBYVL	Investigative	Cholinesterase (BCHE) increases the hydrolysis of Butyrylthiocholine.	[49]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Heroin diacetylmorphine	DMDBWHY	Approved	Cholinesterase (BCHE) increases the metabolism of Heroin diacetylmorphine.	[40]
Acetylcholine	DMDF79Z	Approved	Cholinesterase (BCHE) increases the degradation of Acetylcholine.	[41]

This DOT Affected the Drug Response of 6 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Dibucaine	DMF9G7L	Approved	Cholinesterase (BCHE) decreases the response to substance of Dibucaine.	[42]
Donepezil	DMIYG7Z	Approved	Cholinesterase (BCHE) increases the Dizziness ADR of Donepezil.	[43]
Succinylcholine	DM2ET1M	Approved	Cholinesterase (BCHE) increases the response to substance of Succinylcholine.	[44]
Neostigmine	DM6T2J3	Approved	Cholinesterase (BCHE) affects the response to substance of Neostigmine.	[45]
Mivacurium	DM473VD	Approved	Cholinesterase (BCHE) increases the response to substance of Mivacurium.	[46]
Eptastigmine	DMTV7ZM	Phase 3	Cholinesterase (BCHE) increases the Dizziness ADR of Eptastigmine.	[43]

52 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 Cholinesterase (BCHE).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cholinesterase (BCHE).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cholinesterase (BCHE).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Cholinesterase (BCHE).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Cholinesterase (BCHE).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Cholinesterase (BCHE).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Cholinesterase (BCHE).	[8]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Cholinesterase (BCHE).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Cholinesterase (BCHE).	[9]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Cholinesterase (BCHE).	[10]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Cholinesterase (BCHE).	[11]
Malathion	DMXZ84M	Approved	Malathion decreases the activity of Cholinesterase (BCHE).	[12]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the activity of Cholinesterase (BCHE).	[13]
Bicalutamide	DMZMSPF	Approved	Bicalutamide decreases the expression of Cholinesterase (BCHE).	[14]
Promethazine	DM6I5GR	Approved	Promethazine decreases the activity of Cholinesterase (BCHE).	[15]
Tacrine	DM51FY6	Approved	Tacrine decreases the activity of Cholinesterase (BCHE).	[16]
Isoflurophate	DMBSK7X	Approved	Isoflurophate decreases the activity of Cholinesterase (BCHE).	[17]
Diphenhydramine	DMKQTBA	Approved	Diphenhydramine decreases the activity of Cholinesterase (BCHE).	[15]
Rivastigmine	DMG629M	Approved	Rivastigmine decreases the activity of Cholinesterase (BCHE).	[18]
Chlorpheniramine	DM5URA2	Approved	Chlorpheniramine decreases the activity of Cholinesterase (BCHE).	[15]
Phenelzine	DMHIDUE	Approved	Phenelzine decreases the expression of Cholinesterase (BCHE).	[19]
Galantamine	DMEO794	Approved	Galantamine decreases the activity of Cholinesterase (BCHE).	[20]
Mepyramine	DMB4SFH	Approved	Mepyramine decreases the activity of Cholinesterase (BCHE).	[15]
Bambuterol	DMKLSHF	Approved	Bambuterol decreases the activity of Cholinesterase (BCHE).	[21]
Promazine	DMZAL7W	Approved	Promazine decreases the activity of Cholinesterase (BCHE).	[15]
Ethopropazine	DM0N3L7	Approved	Ethopropazine decreases the activity of Cholinesterase (BCHE).	[16]
Echothiophate Iodide	DMSNVGB	Approved	Echothiophate Iodide decreases the activity of Cholinesterase (BCHE).	[17]
Tripelennamine	DMZBU15	Approved	Tripelennamine decreases the activity of Cholinesterase (BCHE).	[15]
Dimenhydrinate	DM264B3	Approved	Dimenhydrinate decreases the activity of Cholinesterase (BCHE).	[15]
Decamethonium	DMSBRUW	Approved	Decamethonium decreases the activity of Cholinesterase (BCHE).	[22]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Cholinesterase (BCHE).	[8]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Cholinesterase (BCHE).	[23]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Cholinesterase (BCHE).	[24]
Methanesulfonyl fluoride	DMS7FRI	Phase 2	Methanesulfonyl fluoride decreases the activity of Cholinesterase (BCHE).	[22]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Cholinesterase (BCHE).	[26]
Physostigmine	DM2N0TO	Discontinued in Phase 2	Physostigmine decreases the activity of Cholinesterase (BCHE).	[27]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Cholinesterase (BCHE).	[28]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Cholinesterase (BCHE).	[29]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the activity of Cholinesterase (BCHE).	[12]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the activity of Cholinesterase (BCHE).	[30]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos decreases the activity of Cholinesterase (BCHE).	[31]
Paraoxon	DMN4ZKC	Investigative	Paraoxon decreases the activity of Cholinesterase (BCHE).	[32]
Choline	DM5D9YK	Investigative	Choline decreases the activity of Cholinesterase (BCHE).	[33]
Linoleic acid	DMDGPY9	Investigative	Linoleic acid increases the expression of Cholinesterase (BCHE).	[34]
Chlorphrifos oxon	DMGBT68	Investigative	Chlorphrifos oxon decreases the activity of Cholinesterase (BCHE).	[35]
Fenthion	DMKEG49	Investigative	Fenthion decreases the activity of Cholinesterase (BCHE).	[36]
Alpha-linolenic acid	DMY64HE	Investigative	Alpha-linolenic acid increases the expression of Cholinesterase (BCHE).	[34]
Propidium	DMZ1FRS	Investigative	Propidium decreases the activity of Cholinesterase (BCHE).	[22]
[14C]TEA	DM6SFYH	Investigative	[14C]TEA decreases the activity of Cholinesterase (BCHE).	[22]
S 3025	DMZN0RW	Investigative	S 3025 decreases the activity of Cholinesterase (BCHE).	[37]
Iso-OMPA	DMFX16H	Investigative	Iso-OMPA decreases the activity of Cholinesterase (BCHE).	[37]
Tetramethylammonium Ion	DMLEPYN	Investigative	Tetramethylammonium Ion decreases the activity of Cholinesterase (BCHE).	[22]

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 affects the methylation of Cholinesterase (BCHE).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tiapamil	DMWSI0H	Investigative	Tiapamil affects the binding of Cholinesterase (BCHE).	[38]

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