Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT40A9WH)

• DOT Name: Methylated-DNA--protein-cysteine methyltransferase (MGMT)
• Synonyms: EC 2.1.1.63; 6-O-methylguanine-DNA methyltransferase; MGMT; O-6-methylguanine-DNA-alkyltransferase
• Gene Name: MGMT
• UniProt ID: MGMT_HUMAN
• PDB ID: 1EH6; 1EH7; 1EH8; 1QNT; 1T38; 1T39; 1YFH
• EC Number: 2.1.1.63
• Pfam ID: PF01035 ; PF02870
• Sequence:
  MDKDCEMKRTTLDSPLGKLELSGCEQGLHEIKLLGKGTSAADAVEVPAPAAVLGGPEPLM
  QCTAWLNAYFHQPEAIEEFPVPALHHPVFQQESFTRQVLWKLLKVVKFGEVISYQQLAAL
  AGNPKAARAVGGAMRGNPVPILIPCHRVVCSSGAVGNYSGGLAVKEWLLAHEGHRLGKPG
  LGGSSGLAGAWLKGAGATSGSPPAGRN
• Function: Involved in the cellular defense against the biological effects of O6-methylguanine (O6-MeG) and O4-methylthymine (O4-MeT) in DNA. Repairs the methylated nucleobase in DNA by stoichiometrically transferring the methyl group to a cysteine residue in the enzyme. This is a suicide reaction: the enzyme is irreversibly inactivated.
• Reactome Pathway: MGMT-mediated DNA damage reversal (R-HSA-5657655)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 10 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Methylated-DNA--protein-cysteine methyltransferase (MGMT) decreases the response to substance of Doxorubicin.	[36]
Temozolomide	DMKECZD	Approved	Methylated-DNA--protein-cysteine methyltransferase (MGMT) decreases the response to substance of Temozolomide.	[37]
DTI-015	DMXZRW0	Approved	Methylated-DNA--protein-cysteine methyltransferase (MGMT) decreases the response to substance of DTI-015.	[37]
Mitomycin	DMH0ZJE	Approved	Methylated-DNA--protein-cysteine methyltransferase (MGMT) increases the response to substance of Mitomycin.	[38]
Beta-carotene	DM0RXBT	Approved	Methylated-DNA--protein-cysteine methyltransferase (MGMT) affects the response to substance of Beta-carotene.	[39]
Fotemustine	DMV62ED	Approved	Methylated-DNA--protein-cysteine methyltransferase (MGMT) decreases the response to substance of Fotemustine.	[40]
Lomustine	DMMWSUL	Approved	Methylated-DNA--protein-cysteine methyltransferase (MGMT) decreases the response to substance of Lomustine.	[41]
Streptozocin	DMOF7AT	Approved	Methylated-DNA--protein-cysteine methyltransferase (MGMT) decreases the response to substance of Streptozocin.	[38]
CYSTEMUSTINE	DM0DT45	Phase 2	Methylated-DNA--protein-cysteine methyltransferase (MGMT) affects the response to substance of CYSTEMUSTINE.	[42]
acrolein	DMAMCSR	Investigative	Methylated-DNA--protein-cysteine methyltransferase (MGMT) decreases the response to substance of acrolein.	[43]

36 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 Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[4]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[6]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[7]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[8]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[9]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[10]
Topotecan	DMP6G8T	Approved	Topotecan decreases the expression of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[9]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[11]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the expression of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[12]
Acocantherin	DM7JT24	Approved	Acocantherin decreases the expression of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[13]
Hydralazine	DMU8JGH	Approved	Hydralazine increases the expression of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[15]
Dacarbazine	DMNPZL4	Approved	Dacarbazine decreases the activity of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[16]
Silymarin	DMXBYQR	Phase 4	Silymarin increases the expression of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[17]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[18]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[19]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[17]
Camptothecin	DM6CHNJ	Phase 3	Camptothecin decreases the expression of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[9]
Guanine	DMIWLJE	Phase 3	Guanine decreases the activity of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[20]
Laromustine	DMH2EA1	Phase 3	Laromustine decreases the activity of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[21]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[22]
Procysteine	DMF9RB4	Phase 2	Procysteine increases the expression of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[25]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[26]
PMID26560530-Compound-34	DMLGZPO	Patented	PMID26560530-Compound-34 increases the expression of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[17]
Lomeguatrib	DMW9MOK	Discontinued in Phase 2	Lomeguatrib decreases the activity of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[27]
SB 203580	DMAET6F	Terminated	SB 203580 decreases the expression of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[28]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[30]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[31]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[32]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[33]
U0126	DM31OGF	Investigative	U0126 decreases the expression of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[28]
Buthionine sulfoximine	DMJ46CB	Investigative	Buthionine sulfoximine decreases the activity of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[17]
methyl isocyanate	DME4JGF	Investigative	methyl isocyanate decreases the activity of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[5]
Phenytoin	DMNOKBV	Approved	Phenytoin increases the methylation of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[29]
Aminohippuric acid	DMUN54G	Investigative	Aminohippuric acid decreases the methylation of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[23]
Disulfiram	DMCL2OK	Phase 2 Trial	Disulfiram increases the degradation of Methylated-DNA--protein-cysteine methyltransferase (MGMT).	[24]

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