Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2H8HG6)

• DOT Name: Acetylcholinesterase (ACHE)
• Synonyms: AChE; EC 3.1.1.7
• Gene Name: ACHE
• UniProt ID: ACES_HUMAN
• PDB ID: 1B41 ; 1F8U ; 1VZJ ; 2X8B ; 3LII ; 4BDT ; 4EY4 ; 4EY5 ; 4EY6 ; 4EY7 ; 4EY8 ; 4M0E ; 4M0F ; 4PQE ; 5FOQ ; 5FPQ ; 5HF5 ; 5HF6 ; 5HF8 ; 5HF9 ; 5HFA ; 5HQ3 ; 6CQT ; 6CQU ; 6CQV ; 6CQW ; 6CQX ; 6CQY ; 6CQZ ; 6F25 ; 6NEA ; 6NTG ; 6NTH ; 6NTK ; 6NTL ; 6NTM ; 6NTN ; 6NTO ; 6O4W ; 6O4X ; 6O50 ; 6O52 ; 6O5R ; 6O5S ; 6O5V ; 6O66 ; 6O69 ; 6U34 ; 6U37 ; 6U3P ; 6WUV ; 6WUY ; 6WUZ ; 6WV1 ; 6WVC ; 6WVO ; 6WVP ; 6WVQ ; 6ZWE ; 7D9O ; 7D9P ; 7D9Q ; 7E3D ; 7E3H ; 7RB5 ; 7RB6 ; 7RB7 ; 7XN1 ; 8AEN ; 8AEV ; 8DT2 ; 8DT4 ; 8DT5 ; 8DT7
• EC Number: 3.1.1.7
• Pfam ID: PF08674 ; PF00135
• Sequence:
  MRPPQCLLHTPSLASPLLLLLLWLLGGGVGAEGREDAELLVTVRGGRLRGIRLKTPGGPV
  SAFLGIPFAEPPMGPRRFLPPEPKQPWSGVVDATTFQSVCYQYVDTLYPGFEGTEMWNPN
  RELSEDCLYLNVWTPYPRPTSPTPVLVWIYGGGFYSGASSLDVYDGRFLVQAERTVLVSM
  NYRVGAFGFLALPGSREAPGNVGLLDQRLALQWVQENVAAFGGDPTSVTLFGESAGAASV
  GMHLLSPPSRGLFHRAVLQSGAPNGPWATVGMGEARRRATQLAHLVGCPPGGTGGNDTEL
  VACLRTRPAQVLVNHEWHVLPQESVFRFSFVPVVDGDFLSDTPEALINAGDFHGLQVLVG
  VVKDEGSYFLVYGAPGFSKDNESLISRAEFLAGVRVGVPQVSDLAAEAVVLHYTDWLHPE
  DPARLREALSDVVGDHNVVCPVAQLAGRLAAQGARVYAYVFEHRASTLSWPLWMGVPHGY
  EIEFIFGIPLDPSRNYTAEEKIFAQRLMRYWANFARTGDPNEPRDPKAPQWPPYTAGAQQ
  YVSLDLRPLEVRRGLRAQACAFWNRFLPKLLSATDTLDEAERQWKAEFHRWSSYMVHWKN
  QFDHYSKQDRCSDL
• Function: Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis.
• Tissue Specificity: Isoform H is highly expressed in erythrocytes.
• KEGG Pathway:
  Glycerophospholipid metabolism (hsa00564)
  Cholinergic sy.pse (hsa04725)
• Reactome Pathway:
  Synthesis of PC (R-HSA-1483191)
  Synthesis, secretion, and deacylation of Ghrelin (R-HSA-422085)
  Neurotransmitter clearance (R-HSA-112311)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Indomethacin	DMSC4A7	Approved	Acetylcholinesterase (ACHE) increases the Injury ADR of Indomethacin.	[45]

This DOT Affected the Biotransformations of 5 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Morphine	DMRMS0L	Approved	Acetylcholinesterase (ACHE) increases the chemical synthesis of Morphine.	[46]
Acetylcholine	DMDF79Z	Approved	Acetylcholinesterase (ACHE) increases the hydrolysis of Acetylcholine.	[47]
Carbachol	DMX9K8F	Approved	Acetylcholinesterase (ACHE) increases the hydrolysis of Carbachol.	[48]
Remdesivir	DMBFZ6L	Phase 3 Trial	Acetylcholinesterase (ACHE) increases the hydrolysis of Remdesivir.	[49]
Butyrylthiocholine	DMOBYVL	Investigative	Acetylcholinesterase (ACHE) increases the hydrolysis of Butyrylthiocholine.	[50]

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 Acetylcholinesterase (ACHE).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Acetylcholinesterase (ACHE).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Acetylcholinesterase (ACHE).	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Acetylcholinesterase (ACHE).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the activity of Acetylcholinesterase (ACHE).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Acetylcholinesterase (ACHE).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Acetylcholinesterase (ACHE).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Acetylcholinesterase (ACHE).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Acetylcholinesterase (ACHE).	[7]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Acetylcholinesterase (ACHE).	[8]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Acetylcholinesterase (ACHE).	[9]
Ethanol	DMDRQZU	Approved	Ethanol increases the activity of Acetylcholinesterase (ACHE).	[10]
Malathion	DMXZ84M	Approved	Malathion decreases the activity of Acetylcholinesterase (ACHE).	[11]
Colchicine	DM2POTE	Approved	Colchicine increases the activity of Acetylcholinesterase (ACHE).	[12]
Orlistat	DMRJSP8	Approved	Orlistat decreases the activity of Acetylcholinesterase (ACHE).	[13]
Imipramine	DM2NUH3	Approved	Imipramine decreases the activity of Acetylcholinesterase (ACHE).	[14]
Tacrine	DM51FY6	Approved	Tacrine decreases the activity of Acetylcholinesterase (ACHE).	[15]
Isoflurophate	DMBSK7X	Approved	Isoflurophate decreases the activity of Acetylcholinesterase (ACHE).	[16]
Hexachlorophene	DMLKSE0	Approved	Hexachlorophene decreases the activity of Acetylcholinesterase (ACHE).	[13]
Rivastigmine	DMG629M	Approved	Rivastigmine decreases the activity of Acetylcholinesterase (ACHE).	[17]
Scopolamine	DMOM8AL	Approved	Scopolamine increases the activity of Acetylcholinesterase (ACHE).	[18]
Methylene blue	DMJAPE7	Approved	Methylene blue decreases the activity of Acetylcholinesterase (ACHE).	[13]
L-glutamic acid	DM4PUDW	Approved	L-glutamic acid increases the activity of Acetylcholinesterase (ACHE).	[12]
Galantamine	DMEO794	Approved	Galantamine decreases the activity of Acetylcholinesterase (ACHE).	[19]
Moxisylyte	DMFCLYW	Approved	Moxisylyte decreases the activity of Acetylcholinesterase (ACHE).	[13]
Bambuterol	DMKLSHF	Approved	Bambuterol decreases the activity of Acetylcholinesterase (ACHE).	[20]
Neostigmine	DM6T2J3	Approved	Neostigmine decreases the activity of Acetylcholinesterase (ACHE).	[21]
Dyclonine	DMU6OFP	Approved	Dyclonine decreases the activity of Acetylcholinesterase (ACHE).	[13]
Pancuronium	DMB0VY8	Approved	Pancuronium decreases the activity of Acetylcholinesterase (ACHE).	[22]
Edrophonium	DMCRQHB	Approved	Edrophonium decreases the activity of Acetylcholinesterase (ACHE).	[14]
MEPTAZINOL	DMPSB8F	Approved	MEPTAZINOL decreases the activity of Acetylcholinesterase (ACHE).	[13]
Chlorhexidine	DMQ9MVG	Approved	Chlorhexidine decreases the activity of Acetylcholinesterase (ACHE).	[13]
Acetohydroxamic Acid	DMYX7NI	Approved	Acetohydroxamic Acid decreases the activity of Acetylcholinesterase (ACHE).	[23]
Berberine	DMC5Q8X	Phase 4	Berberine decreases the activity of Acetylcholinesterase (ACHE).	[13]
Chlorpromazine	DMBGZI3	Phase 3 Trial	Chlorpromazine decreases the activity of Acetylcholinesterase (ACHE).	[24]
Eptastigmine	DMTV7ZM	Phase 3	Eptastigmine decreases the activity of Acetylcholinesterase (ACHE).	[25]
Itopride	DM7MLTR	Phase 3	Itopride decreases the activity of Acetylcholinesterase (ACHE).	[14]
Ecopipam	DMS9R43	Phase 3	Ecopipam decreases the activity of Acetylcholinesterase (ACHE).	[13]
Synthetic neutrophil inhibitor peptide	DM83E5B	Phase 1	Synthetic neutrophil inhibitor peptide decreases the activity of Acetylcholinesterase (ACHE).	[27]
VELNACRINE	DMUB0EC	Discontinued in Phase 3	VELNACRINE decreases the activity of Acetylcholinesterase (ACHE).	[13]
Physostigmine	DM2N0TO	Discontinued in Phase 2	Physostigmine decreases the activity of Acetylcholinesterase (ACHE).	[28]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the activity of Acetylcholinesterase (ACHE).	[30]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the activity of Acetylcholinesterase (ACHE).	[31]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos increases the expression of Acetylcholinesterase (ACHE).	[33]
Rutin	DMEHRAJ	Investigative	Rutin decreases the expression of Acetylcholinesterase (ACHE).	[34]
Paraoxon	DMN4ZKC	Investigative	Paraoxon decreases the activity of Acetylcholinesterase (ACHE).	[35]
Choline	DM5D9YK	Investigative	Choline decreases the activity of Acetylcholinesterase (ACHE).	[36]
Staurosporine	DM0E9BR	Investigative	Staurosporine increases the activity of Acetylcholinesterase (ACHE).	[37]
Chlorphrifos oxon	DMGBT68	Investigative	Chlorphrifos oxon decreases the activity of Acetylcholinesterase (ACHE).	[38]
Fenthion	DMKEG49	Investigative	Fenthion decreases the activity of Acetylcholinesterase (ACHE).	[39]
Lefaxin	DM0CEY3	Investigative	Lefaxin decreases the activity of Acetylcholinesterase (ACHE).	[40]
Propidium	DMZ1FRS	Investigative	Propidium decreases the activity of Acetylcholinesterase (ACHE).	[14]
Chebulinic acid	DMR8HKC	Investigative	Chebulinic acid decreases the expression of Acetylcholinesterase (ACHE).	[41]
MEMOQUIN	DM9S30P	Investigative	MEMOQUIN decreases the activity of Acetylcholinesterase (ACHE).	[42]
WR85915	DM9V0KP	Investigative	WR85915 decreases the activity of Acetylcholinesterase (ACHE).	[13]
TRIMEDOXIME	DMPXHTY	Investigative	TRIMEDOXIME decreases the activity of Acetylcholinesterase (ACHE).	[44]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride decreases the stability of Acetylcholinesterase (ACHE).	[32]
Tiapamil	DMWSI0H	Investigative	Tiapamil affects the binding of Acetylcholinesterase (ACHE).	[43]

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