Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTJ8DV7)

• DTT Name: O-6-methylguanine-DNA-alkyltransferase (MGMT)
• Synonyms: Methylated-DNA--protein-cysteine methyltransferase; Human O(6)-alkylguanine-DNA alkyltransferase; 6-O-methylguanine-DNA methyltransferase
• Gene Name: MGMT
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Methyltransferase
• UniProt ID: MGMT_HUMAN
• TTD ID: T24587
• EC Number: EC 2.1.1.63
• Sequence:
  MDKDCEMKRTTLDSPLGKLELSGCEQGLHEIKLLGKGTSAADAVEVPAPAAVLGGPEPLM
  QCTAWLNAYFHQPEAIEEFPVPALHHPVFQQESFTRQVLWKLLKVVKFGEVISYQQLAAL
  AGNPKAARAVGGAMRGNPVPILIPCHRVVCSSGAVGNYSGGLAVKEWLLAHEGHRLGKPG
  LGGSSGLAGAWLKGAGATSGSPPAGRN
• Function: 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. Involved in the cellular defense against the biological effects of O6-methylguanine (O6-MeG) and O4-methylthymine (O4-MeT) in DNA.
• Reactome Pathway: MGMT-mediated DNA damage reversal (R-HSA-5657655)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
O6-Benzylguanine alkylade	DM3L2GT	Sarcoma	2A60-2C35	Phase 3	[1]

6 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
6-Allyloxy-9H-purin-2-ylamine	DMI2XUQ	Discovery agent	N.A.	Investigative	[2]
6-Benzyloxy-5-nitro-pyrimidine-2,4-diamine	DMK8XIO	Discovery agent	N.A.	Investigative	[3]
6-Benzyloxy-5-nitroso-pyrimidine-2,4-diamine	DMUFSE2	Discovery agent	N.A.	Investigative	[3]
6-Benzyloxy-9H-purin-2-ylamine	DMFI7A8	Discovery agent	N.A.	Investigative	[3]
Benzylcysteine	DMTCYHM	Discovery agent	N.A.	Investigative	[4]
S-Methylcysteine	DMAMRKS	Discovery agent	N.A.	Investigative	[4]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Sarcoma	2C82	Muscle tissue	1.21E-12	-0.31	-0.83

References

• [1] Phase II trial of temozolomide plus o6-benzylguanine in adults with recurrent, temozolomide-resistant malignant glioma. J Clin Oncol. 2009 Mar 10;27(8):1262-7.
• [2] Resistance-modifying agents. 8. Inhibition of O(6)-alkylguanine-DNA alkyltransferase by O(6)-alkenyl-, O(6)-cycloalkenyl-, and O(6)-(2-oxoalkyl)gua... J Med Chem. 2000 Nov 2;43(22):4071-83.
• [3] Inhibition of human O6-alkylguanine-DNA alkyltransferase and potentiation of the cytotoxicity of chloroethylnitrosourea by 4(6)-(benzyloxy)-2,6(4)-... J Med Chem. 1998 Feb 12;41(4):503-8.
• [4] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.