MGMT
MGMT encodes O6-methylguanine-DNA methyltransferase, also called AGT, a DNA repair protein that removes alkyl groups from O6-alkylguanine adducts[1]. Mechanistically, MGMT repairs cytotoxic O6-methylguanine and O6-chloroethylguanine lesions induced by methylating or chloroethylating agents, thereby limiting DNA damage signaling and alkylating-drug cytotoxicity[2][3]. In glioma, MGMT promoter methylation silences MGMT expression and predicts clinical response to alkylating agents, including temozolomide[4][5]. Compared with separate isoform targets, the retrieved literature describes MGMT/AGT as the same repair protein, so isoform-specific claims require additional evidence[1]. For experimental applications, O6-benzylguanine and O6-(4-bromothenyl)guanine have been used to inactivate MGMT, but normal-tissue MGMT inhibition can increase alkylating-drug toxicity[6].
References:
- [1]. Fang Q. The Versatile Attributes of MGMT: Its Repair Mechanism, et al. The Versatile Attributes of MGMT: Its Repair Mechanism, Crosstalk with Other DNA Repair Pathways, and Its Role in Cancer. Cancers (Basel). 2024 Jan 11;16(2):331. [Content Brief]
- [2]. Kaina B, et al. MGMT: key node in the battle against genotoxicity, carcinogenicity and apoptosis induced by alkylating agents. DNA Repair (Amst). 2007 Aug 1;6(8):1079-99. [Content Brief]
- [3]. Fan CH, et al. O6-methylguanine DNA methyltransferase as a promising target for the treatment of temozolomide-resistant gliomas. Cell Death Dis. 2013 Oct 24;4(10):e876. [Content Brief]
- [4]. Esteller M, et al. Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med. 2000 Nov 9;343(19):1350-4. [Content Brief]
- [5]. Hegi ME, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005 Mar 10;352(10):997-1003. [Content Brief]
- [6]. Kaina B, et al. Targeting O⁶-methylguanine-DNA methyltransferase with specific inhibitors as a strategy in cancer therapy. Cell Mol Life Sci. 2010 Nov;67(21):3663-81. [Content Brief]
All Product Categories
-
MGMT Related Products (5)
-
Antibodies (1)
-
O6BTG-octylglucoside
0 ImagesCat. No.: HY-13057CAS No.: 382607-78-5Synonyms: Glucose-conjugated MGMT inhibitorO6BTG-octylglucoside is a potent O6-methylguanine-DNAmethyl-transferase (MGMT) inhibitor, with IC50s of 32 nM in vitro (cell extracts) and 10 nM in HeLa S3 cells.
-
Anticancer agent 333
0 ImagesCat. No.: HY-186228CAS No.: 3075414-82-0Anticancer agent 333 is a tetrazinone anticancer agent with broad-spectrum anticancer activity, targeting MGMT/AGT-deficient cancer cells (IC50≤20 μM). Anticancer agent 333 exhibits favorable safety profiles in rat and canine animal models. Anticancer agent 333 can be used for the research of MGMT-deficient cancers and related tumors.
-
MGMT-IN-1
0 ImagesCat. No.: HY-180540MGMT-IN-1 (Compound 2) is a light-activated MGMT inhibitor. MGMT-IN-1 can effectively enhance the cytotoxicity of Temozolomide (TMZ) (HY-17364) only under light conditions, significantly increasing the DNA damage caused by TMZ. MGMT-IN-1 can be used for the study of chordoma.
-
Hedgehog IN-11
0 ImagesCat. No.: HY-175299Hedgehog IN-11 is an orally active Hedgehog inhibitor. Hedgehog IN-11 downregulates the expression of O6-methylguanine-DNA methyltransferase (MGMT) to impair the Temozolomide (TMZ) (HY-17364) resistance by inhibiting the Hedgehog pathway. Hedgehog IN-11 shows improved inhibition of cell migration and invasion, and induced cell apoptosis in TMZ-resistant GBM cell lines. Hedgehog IN-11 is predicted by computer simulation to have good blood-brain barrier penetration. Hedgehog IN-11 can be used for the study of glioblastoma (GBM).
