Target Information
| Target General Infomation | |||||
|---|---|---|---|---|---|
| Target ID |
T24587
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| Former ID |
TTDR00624
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| Target Name |
Methylated-DNA--protein-cysteine methyltransferase
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| Gene Name |
MGMT
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| Synonyms |
6-O-methylguanine-DNA methyltransferase; Human O(6)-alkylguanine-DNA alkyltransferase; O-6-methylguanine-DNA-alkyltransferase; MGMT
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| Target Type |
Clinical Trial
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| 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.
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| BioChemical Class |
Methyltransferase superfamily
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| Target Validation |
T24587
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| UniProt ID | |||||
| EC Number |
EC 2.1.1.63
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| Sequence |
MDKDCEMKRTTLDSPLGKLELSGCEQGLHEIKLLGKGTSAADAVEVPAPAAVLGGPEPLM
QCTAWLNAYFHQPEAIEEFPVPALHHPVFQQESFTRQVLWKLLKVVKFGEVISYQQLAAL AGNPKAARAVGGAMRGNPVPILIPCHRVVCSSGAVGNYSGGLAVKEWLLAHEGHRLGKPG LGGSSGLAGAWLKGAGATSGSPPAGRN |
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| Drugs and Mode of Action | |||||
| Drug(s) | O6-Benzylguanine alkylade | Drug Info | Phase 3 | Sarcoma | [1], [2] |
| Inhibitor | 6-Allyloxy-9H-purin-2-ylamine | Drug Info | [3] | ||
| 6-Benzyloxy-5-nitro-pyrimidine-2,4-diamine | Drug Info | [4] | |||
| 6-Benzyloxy-5-nitroso-pyrimidine-2,4-diamine | Drug Info | [4] | |||
| 6-Benzyloxy-9H-purin-2-ylamine | Drug Info | [4] | |||
| Benzylcysteine | Drug Info | [5] | |||
| S-Methylcysteine | Drug Info | [5] | |||
| Modulator | O6-Benzylguanine alkylade | Drug Info | [1], [2] | ||
| Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
| TEP | EXP Info | ||||
| Pathways | |||||
| WikiPathways | DNA Damage Reversal | ||||
| References | |||||
| REF 1 | Phase 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 2 | 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. | ||||
| REF 3 | J 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 4 | J 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 5 | How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | ||||
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