Home >> Research Area >>Others>>MGMT>> Glucose-conjugated MGMT inhibitor

Glucose-conjugated MGMT inhibitor

Glucose-conjugated MGMT inhibitor CAS# 382607-78-5

Glucose-conjugated MGMT inhibitor

Catalog No. BCC1597----Order now to get a substantial discount!

Product Name & Size Price Stock
Glucose-conjugated MGMT inhibitor: 5mg $253 In Stock
Glucose-conjugated MGMT inhibitor: 10mg Please Inquire In Stock
Glucose-conjugated MGMT inhibitor: 20mg Please Inquire Please Inquire
Glucose-conjugated MGMT inhibitor: 50mg Please Inquire Please Inquire
Glucose-conjugated MGMT inhibitor: 100mg Please Inquire Please Inquire
Glucose-conjugated MGMT inhibitor: 200mg Please Inquire Please Inquire
Glucose-conjugated MGMT inhibitor: 500mg Please Inquire Please Inquire
Glucose-conjugated MGMT inhibitor: 1000mg Please Inquire Please Inquire
Related Products

Quality Control of Glucose-conjugated MGMT inhibitor

Number of papers citing our products

Chemical structure

Glucose-conjugated MGMT inhibitor

3D structure

Chemical Properties of Glucose-conjugated MGMT inhibitor

Cas No. 382607-78-5 SDF Download SDF
PubChem ID 10438805 Appearance Powder
Formula C24H34BrN5O7S M.Wt 616.53
Type of Compound N/A Storage Desiccate at -20°C
Synonyms O6BTG-C8-βGlu
Solubility DMSO : 100 mg/mL (162.20 mM; Need ultrasonic)
Chemical Name (2R,3R,4S,5S,6R)-2-[8-[2-amino-6-[(4-bromothiophen-2-yl)methoxy]purin-9-yl]octoxy]-6-(hydroxymethyl)oxane-3,4,5-triol
SMILES C1=C(SC=C1Br)COC2=NC(=NC3=C2N=CN3CCCCCCCCOC4C(C(C(C(O4)CO)O)O)O)N
Standard InChIKey WAAZBVOGWRQLMB-PUIBNRJISA-N
Standard InChI InChI=1S/C24H34BrN5O7S/c25-14-9-15(38-12-14)11-36-22-17-21(28-24(26)29-22)30(13-27-17)7-5-3-1-2-4-6-8-35-23-20(34)19(33)18(32)16(10-31)37-23/h9,12-13,16,18-20,23,31-34H,1-8,10-11H2,(H2,26,28,29)/t16-,18-,19+,20-,23-/m1/s1
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Biological Activity of Glucose-conjugated MGMT inhibitor

DescriptionGlucose-conjugated MGMT inhibitor 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.In Vitro:Glucose-conjugated MGMT inhibitor (O6BTG-octylglucoside) is a potent and non-toxic MGMT inhibitor, with IC50s of 32 nM in vitro (cell extracts) and 10 nM in HeLa S3 cells[1].

References:
[1]. Jost Reinhard, et al. Inactivation of O6-methylguanine-DNA methyltransferase by glucose-conjugated inhibitors. Int.J.Cancer. (2001) 93,373-379.

Protocol

Kinase Assay [1]
For the assays, 100 mg cell extract protein are used. In each assay, a negative and a positive sample, HeLa MR (MGMT-deficient) and HeLa S3 cell extract, respectively, are included. Incubation occurs in buffer contain-ing 700 mM HEPES-KOH (pH 7.8), 10 mM dithiothreitol and 50 mM EDTA for 90 min, which is the optimal time span for the reaction to be completed. Data are expressed as femtomoles of radioactivity trans-ferred from 3H-methylnitrosourea-labeled DNA to protein per milligram of protein within Glucose-conjugated MGMT inhibitor[1].

References:
[1]. Jost Reinhard, et al. Inactivation of O6-methylguanine-DNA methyltransferase by glucose-conjugated inhibitors. Int.J.Cancer. (2001) 93,373-379.

Glucose-conjugated MGMT inhibitor Dilution Calculator

Concentration (start)
x
Volume (start)
=
Concentration (final)
x
Volume (final)
 
 
 
C1
V1
C2
V2

calculate

Glucose-conjugated MGMT inhibitor Molarity Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
g/mol

calculate

Preparing Stock Solutions of Glucose-conjugated MGMT inhibitor

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 1.622 mL 8.1099 mL 16.2198 mL 32.4396 mL 40.5495 mL
5 mM 0.3244 mL 1.622 mL 3.244 mL 6.4879 mL 8.1099 mL
10 mM 0.1622 mL 0.811 mL 1.622 mL 3.244 mL 4.055 mL
50 mM 0.0324 mL 0.1622 mL 0.3244 mL 0.6488 mL 0.811 mL
100 mM 0.0162 mL 0.0811 mL 0.1622 mL 0.3244 mL 0.4055 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

Organizitions Citing Our Products recently

 
 
 

Calcutta University

University of Minnesota

University of Maryland School of Medicine

University of Illinois at Chicago

The Ohio State University

University of Zurich

Harvard University

Colorado State University

Auburn University

Yale University

Worcester Polytechnic Institute

Washington State University

Stanford University

University of Leipzig

Universidade da Beira Interior

The Institute of Cancer Research

Heidelberg University

University of Amsterdam

University of Auckland
TsingHua University
TsingHua University
The University of Michigan
The University of Michigan
Miami University
Miami University
DRURY University
DRURY University
Jilin University
Jilin University
Fudan University
Fudan University
Wuhan University
Wuhan University
Sun Yat-sen University
Sun Yat-sen University
Universite de Paris
Universite de Paris
Deemed University
Deemed University
Auckland University
Auckland University
The University of Tokyo
The University of Tokyo
Korea University
Korea University

Background on Glucose-conjugated MGMT inhibitor

O6BTG-C8-βGlu is a glucose-conjugated MGMT inhibitor with IC50 values of 32 nM in vitro and 10 nM on HeLa S3 cell; the parent compound O6BTG's IC50 is 9 nM(in vitro).

Featured Products
New Products
 

References on Glucose-conjugated MGMT inhibitor

Synthesis of 131I-labeled glucose-conjugated inhibitors of O6-methylguanine-DNA methyltransferase (MGMT) and comparison with nonconjugated inhibitors as potential tools for in vivo MGMT imaging.[Pubmed:16392811]

J Med Chem. 2006 Jan 12;49(1):263-72.

O(6)-Substituted guanine derivatives are powerful agents used for tumor cell sensitization by inhibition of the DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT). To provide targeted accumulation of MGMT inhibitors in tumor tissue as well as tools for in vivo imaging, we synthesized iodinated C(8)-alkyl-linked glucose conjugates of 2-amino-6-(5-iodothenyl)-9H-purine (O(6)-(5-iodothenyl) guanine, ITG) and 2-amino-6-(3-iodobenzyloxy)-9H-purine (O(6)-(5-iodobenzyl) guanine, IBG). These compounds have MGMT inhibitor constants (IC(50) values) of 0.8 and 0.45 microM for ITGG and IBGG, respectively, as determined in HeLa S3 cells after 2-h incubation with inhibitor. To substantiate that the (131)I-(hetero)arylmethylene group at the O(6)-position of guanine is transferred to MGMT, both the glucose conjugated inhibitors ITGG and IBGG and the corresponding nonglucose conjugated compounds ITG and IBG were labeled with iodine-131. The radioiodinations of all compounds with [(131)I]I(-) were performed with radiochemical yields of >70% for the destannylation of the corresponding tri-n-butylstannylated precursors. The binding ability of [(131)I]ITGG, [(131)]IBGG, [(131)I]ITG, and [(131)I]IBG to purified MGMT was tested. All radioactive compounds were substrates for MGMT, as demonstrated using a competitive repair assay. The newly synthesized radioactive inhibitors were utilized to study ex vivo biodistribution in mice, and the tumor-to-blood ratio of tissue uptake of [(131)I]IBG and [(131)I]IBGG was determined to be 0.24 and 0.76 after 0.5 h, respectively.

Inhibition of O6-methylguanine-DNA methyltransferase by glucose-conjugated inhibitors: comparison with nonconjugated inhibitors and effect on fotemustine and temozolomide-induced cell death.[Pubmed:15254145]

J Pharmacol Exp Ther. 2004 Nov;311(2):585-93.

The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) is an important suicide enzyme involved in the defense against O(6)-alkylating mutagens. It also plays a role in the resistance of tumors to anticancer drugs targeting the O(6)-position of guanine, such as temozolomide and fotemustine. Several potent MGMT inhibitors have been developed sensitizing cells to O(6)-alkylating agents. Aimed at targeting MGMT inhibitors to tumor cells, we synthesized MGMT inhibitory compounds conjugated with glucose to improve uptake in tumor cells. Here, we compared O(6)-benzylguanine, O(6)-2-fluoropyridinylmethylguanine (O(6)FPG), O(6)-3-iodobenzylguanine, O(6)-4-bromothenylguanine, and O(6)-5-iodothenylguanine with the corresponding C8-linker beta-d-glucose derivatives. All glucose conjugated inhibitors were 3- to 5-fold less effective than the corresponding nonconjugated drugs as to MGMT inhibition that was measured in cell extracts (in vitro) and cultivated HeLaS3 cells (in vivo). Except for O(6)FPG, IC(50) values of the guanine derivatives applied in vitro and in vivo were correlated. A similar correlation was not obvious for the corresponding glucosides, indicating differences in cellular uptake. C8-alpha-d-glucosides were less effective than beta-glucosides. From the newly developed glucose-conjugated inhibitors tested, O(6)-4-bromothenylguanine-C8-beta-d-glucoside (O(6)BTG-C8-betaGlu) was most potent in inhibiting MGMT both in vitro and in vivo. At a concentration of 0.1 microM, it inhibited cellular MGMT to completion. It was not toxic, even when applied chronically to cells at high dose (up to 20 microM). O(6)BTG-C8-betaGlu strongly potentiated the killing effect of fotemustine and temozolomide, causing reversal from MGMT+ to MGMT- phenotype. Therefore, O(6)BTG-C8-betaGlu seems to be especially suitable for approaching MGMT inhibitor targeting in tumor therapy.

Inactivation of O(6)-methylguanine-DNA methyltransferase by glucose-conjugated inhibitors.[Pubmed:11433402]

Int J Cancer. 2001 Aug 1;93(3):373-9.

The DNA-repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) is a decisive determinant of resistance of tumor cells to methylating and chloroethylating anti-cancer drugs. Therefore, selective inhibition of MGMT in tumors is expected to cause tumor sensitization. Several inhibitors of MGMT have been developed which function in both tumors and normal tissue. To deplete MGMT preferentially in tumors, strategies to target the inhibitor to the tumor tissue need to be developed. Here, we report on the properties of Glucose-conjugated MGMT inhibitors that might be useful for tumor targeting since tumor cells frequently over-express glucose transporter. O(6)-Benzylguanine (O6BG), 8-aza-O(6)-benzylguanine, O(6)-(4-bromothenyl)-guanine (O6BTG) and the corresponding spacer-linked beta-D-glucose conjugates were analyzed comparatively for MGMT-inhibitory activity. Substitution at the N9 position of the purine moiety resulted generally in a reduction in the efficiency with which the inhibitors blocked MGMT. However, the inhibitory activity of the O6BTG conjugates increased with increasing spacer length, and O6BTG conjugated with a C8 spacer with beta-D-glucose was nearly as effective as O6BTG on its own. MGMT was inhibited by the conjugates both in crude cell extracts and upon treatment of intact HeLa cells, indicating efficient uptake of the glucose conjugates into cells. Since the O6BTG-C8-D-glucose conjugate 8-[O(6)-(4-bromothenyl)-guan-9-yl]-octyl-beta-D-glucoside was highly efficient at MGMT inhibition in a non-toxic concentration range, the drug might be a useful tool for specific tumor sensitization.

Description

O6BTG-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.

Keywords:

Glucose-conjugated MGMT inhibitor,382607-78-5,O6BTG-C8-βGlu,Natural Products,MGMT, buy Glucose-conjugated MGMT inhibitor , Glucose-conjugated MGMT inhibitor supplier , purchase Glucose-conjugated MGMT inhibitor , Glucose-conjugated MGMT inhibitor cost , Glucose-conjugated MGMT inhibitor manufacturer , order Glucose-conjugated MGMT inhibitor , high purity Glucose-conjugated MGMT inhibitor

Online Inquiry for:

      Fill out the information below

      • Size:Qty: - +

      * Required Fields

                                      Result: