Target Information

Target General Infomation
Target ID
T24587
Former ID
TTDR00624
Target Name
Methylated-DNA--protein-cysteine methyltransferase
Gene Name
MGMT
Synonyms
6-O-methylguanine-DNA methyltransferase; Human O(6)-alkylguanine-DNA alkyltransferase; O-6-methylguanine-DNA-alkyltransferase; MGMT
Target Type
Clinical Trial
Disease Sarcoma [ICD9: 202.8; ICD10: C81-C86]
Function
Involved in the cellular defense against the biological effects of O6-methylguanine (O6-MeG) in DNA. Repairs alkylated guanine in DNA by stoichiometrically transferring the alkyl group at the O-6 position to a cysteine residue in the enzyme. This is a suicide reaction: the enzyme is irreversibly inactivated.
BioChemical Class
Methyltransferase superfamily
Target Validation
T24587
UniProt ID
P16455
EC Number
EC 2.1.1.63
Sequence
MDKDCEMKRTTLDSPLGKLELSGCEQGLHEIKLLGKGTSAADAVEVPAPAAVLGGPEPLM
QCTAWLNAYFHQPEAIEEFPVPALHHPVFQQESFTRQVLWKLLKVVKFGEVISYQQLAAL
AGNPKAARAVGGAMRGNPVPILIPCHRVVCSSGAVGNYSGGLAVKEWLLAHEGHRLGKPG
LGGSSGLAGAWLKGAGATSGSPPAGRN
Drugs and Mode of Action
Drug(s) O6-Benzylguanine alkylade Drug Info Phase 3 Sarcoma [527774], [529958]
Inhibitor 6-Allyloxy-9H-purin-2-ylamine Drug Info [525899]
6-Benzyloxy-5-nitro-pyrimidine-2,4-diamine Drug Info [534565]
6-Benzyloxy-5-nitroso-pyrimidine-2,4-diamine Drug Info [534565]
6-Benzyloxy-9H-purin-2-ylamine Drug Info [534565]
Benzylcysteine Drug Info [551393]
S-Methylcysteine Drug Info [551393]
Modulator O6-Benzylguanine alkylade Drug Info [527774], [529958]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
WikiPathways DNA Damage Reversal
References
Ref 527774Phase I trial of temozolomide plus O6-benzylguanine for patients with recurrent or progressive malignant glioma. J Clin Oncol. 2005 Oct 1;23(28):7178-87.
Ref 529958Phase 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.
Ref 525899J Med Chem. 2000 Nov 2;43(22):4071-83.Resistance-modifying agents. 8. Inhibition of O(6)-alkylguanine-DNA alkyltransferase by O(6)-alkenyl-, O(6)-cycloalkenyl-, and O(6)-(2-oxoalkyl)guanines and potentiation of temozolomide cytotoxicity in vitro by O(6)-(1-cyclopentenylmethyl)guanine.
Ref 527774Phase I trial of temozolomide plus O6-benzylguanine for patients with recurrent or progressive malignant glioma. J Clin Oncol. 2005 Oct 1;23(28):7178-87.
Ref 529958Phase 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.
Ref 534565J Med Chem. 1998 Feb 12;41(4):503-8.Inhibition of human O6-alkylguanine-DNA alkyltransferase and potentiation of the cytotoxicity of chloroethylnitrosourea by 4(6)-(benzyloxy)-2,6(4)-diamino-5-(nitroor nitroso)pyrimidine derivatives and analogues.
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.

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