Target Information
| Target General Information | Top | |||||
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| Target ID |
T24587
(Former ID: TTDR00624)
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| Target Name |
O-6-methylguanine-DNA-alkyltransferase (MGMT)
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| Synonyms |
Methylated-DNA--protein-cysteine methyltransferase; Human O(6)-alkylguanine-DNA alkyltransferase; 6-O-methylguanine-DNA methyltransferase
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| Gene Name |
MGMT
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Sarcoma [ICD-11: 2A60-2C35] | |||||
| 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.
Click to Show/Hide
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| BioChemical Class |
Methyltransferase
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| UniProt ID | ||||||
| EC Number |
EC 2.1.1.63
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| Sequence |
MDKDCEMKRTTLDSPLGKLELSGCEQGLHEIKLLGKGTSAADAVEVPAPAAVLGGPEPLM
QCTAWLNAYFHQPEAIEEFPVPALHHPVFQQESFTRQVLWKLLKVVKFGEVISYQQLAAL AGNPKAARAVGGAMRGNPVPILIPCHRVVCSSGAVGNYSGGLAVKEWLLAHEGHRLGKPG LGGSSGLAGAWLKGAGATSGSPPAGRN Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| ADReCS ID | BADD_A01844 | |||||
| HIT2.0 ID | T18C4B | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | O6-Benzylguanine alkylade | Drug Info | Phase 3 | Sarcoma | [1], [2] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | O6-Benzylguanine alkylade | Drug Info | [1], [2] | |||
| Inhibitor | [+] 6 Inhibitor drugs | + | ||||
| 1 | 6-Allyloxy-9H-purin-2-ylamine | Drug Info | [3] | |||
| 2 | 6-Benzyloxy-5-nitro-pyrimidine-2,4-diamine | Drug Info | [4] | |||
| 3 | 6-Benzyloxy-5-nitroso-pyrimidine-2,4-diamine | Drug Info | [4] | |||
| 4 | 6-Benzyloxy-9H-purin-2-ylamine | Drug Info | [4] | |||
| 5 | Benzylcysteine | Drug Info | [5] | |||
| 6 | S-Methylcysteine | Drug Info | [5] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| WikiPathways | [+] 1 WikiPathways | + | ||||
| 1 | DNA Damage Reversal | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 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. | |||||
| REF 2 | 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 3 | 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. | |||||
| REF 4 | 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. | |||||
| REF 5 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
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