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Lomeguatrib

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Chemical Structure| 192441-08-0 同义名 : PaTrin-2
CAS号 : 192441-08-0
货号 : A129482
分子式 : C10H8BrN5OS
纯度 : 99%+
分子量 : 326.17
MDL号 : MFCD23703756
存储条件：

粉末 Keep in dark place,Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 55 mg/mL(168.62 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • Transferase

    O6-alkylguanine-DNA-alkyltransferas, IC50:5 nM
描述 MGMT (O6-methylguanine-DNA methyltransferase) is an important DNA repair protein for defending alkylating agents through transferring the alkyl adducts onto a cysteine on the active site of MGMT[3]. Lomeguatrib is an MGMT inhibitor with IC50 of around 6 nM in MCF-7 cells[4]. The U-118 MG cells were treated with a combination treatment of temozolomide with 50 μM of lomeguatrib. The MGMT expression level was decreased and the p53 expression level was increased compared with control as determined by RT-qPCR[5]. In a nude mice bearing human melanoma xenografts model, the lomeguatrib was given at a dose of 20 mg/kg i.p. one hour prior to the temozolomide injection once daily for five days. The combinded treatment of temozolomide and lomeguatrib increased the antitumor activity as the tumour growth was delayed with less toxicity[6].
作用机制 The lomeguatrib act as pseudosubstrates to deplete MGMT. It can covalently transfer the bromothenyl group to the active site cysteine on the protein after ubiquitin-dependent proteolysis[7].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.07mL

0.61mL

0.31mL

15.33mL

3.07mL

1.53mL

30.66mL

6.13mL

3.07mL
参考文献

[1]Clemons M, Kelly J, et al. O6-(4-bromothenyl)guanine reverses temozolomide resistance in human breast tumour MCF-7 cells and xenografts. Br J Cancer. 2005 Nov 14;93(10):1152-6.

[2]McElhinney RS, Donnelly DJ, et al. Inactivation of O6-alkylguanine-DNA alkyltransferase. 1. Novel O6-(hetarylmethyl)guanines having basic rings in the side chain. J Med Chem. 1998 Dec 17;41(26):5265-71.

[3]Kaina B, Christmann M, Naumann S, Roos WP. 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.

[4]Clemons M, Kelly J, Watson AJ, Howell A, McElhinney RS, McMurry TB, Margison GP. O6-(4-bromothenyl)guanine reverses temozolomide resistance in human breast tumour MCF-7 cells and xenografts. Br J Cancer. 2005 Nov 14;93(10):1152-6.

[5]Taspinar M, Ilgaz S, Ozdemir M, Ozkan T, Oztuna D, Canpinar H, Rey JA, Sunguroğlu A, Castresana JS, Ugur HC. Effect of lomeguatrib-temozolomide combination on MGMT promoter methylation and expression in primary glioblastoma tumor cells. Tumour Biol. 2013 Jun;34(3):1935-47.

[6]Middleton MR, Thatcher N, McMurry TB, McElhinney RS, Donnelly DJ, Margison GP. Effect of O6-(4-bromothenyl)guanine on different temozolomide schedules in a human melanoma xenograft model. Int J Cancer. 2002 Aug 10;100(5):615-7.

[7]Khan O, Middleton MR. The therapeutic potential of O6-alkylguanine DNA alkyltransferase inhibitors. Expert Opin Investig Drugs. 2007 Oct;16(10):1573-84.