O(6)-Benzylguanine
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MedKoo CAT#: 540041

CAS#: 19916-73-5

Description: O(6)-Benzylguanine is an MGMT inhibitor that prevents the repair of DNA damage induced by chemotherapeutics. It allows apoptosis and other mechanisms of cell death to occur.

Chemical Structure

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O(6)-Benzylguanine
CAS# 19916-73-5
Instruction

Theoretical Analysis

MedKoo Cat#: 540041
Name: O(6)-Benzylguanine
CAS#: 19916-73-5
Chemical Formula: C12H11N5O
Exact Mass: 241.10
Molecular Weight: 241.250
Elemental Analysis: C, 59.74; H, 4.60; N, 29.03; O, 6.63

Price and Availability

Size Price Availability Quantity
50mg USD 195
250mg USD 440
1g USD 1020
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Synonym: O(6)-Benzylguanine; CCRIS 9383; CCRIS9383; CCRIS-9383; NSC637037; NSC 637037; NSC-637037

IUPAC/Chemical Name: 6-(benzyloxy)-1H-purin-2-amine

InChi Key: KRWMERLEINMZFT-UHFFFAOYSA-N

InChi Code: InChI=1S/C12H11N5O/c13-12-16-10-9(14-7-15-10)11(17-12)18-6-8-4-2-1-3-5-8/h1-5,7H,6H2,(H3,13,14,15,16,17)

SMILES Code: NC1=NC2=NC=NC2=C(OCC3=CC=CC=C3)N1

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Biological target:
In vitro activity:
In vivo activity:

Preparing Stock Solutions

The following data is based on the product molecular weight 241.25 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
In vitro protocol:
In vivo protocol:

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1: Sun G, Zhao L, Fan T, Li S, Zhong R. Investigations on the effect of O(6)-benzylguanine on the formation of dG-dC interstrand cross-links induced by chloroethylnitrosoureas in human glioma cells using stable isotope dilution high-performance liquid chromatography electrospray ionization tandem mass spectrometry. Chem Res Toxicol. 2014 Jul 21;27(7):1253-62. doi: 10.1021/tx500143b. Epub 2014 Jun 17. PubMed PMID: 24914620.

2: Paranjpe A, Bailey NI, Konduri S, Bobustuc GC, Ali-Osman F, Yusuf MA, Punganuru SR, Madala HR, Basak D, Mostofa A, Srivenugopal KS. New insights into estrogenic regulation of O(6)-methylguanine DNA-methyltransferase (MGMT) in human breast cancer cells: Co-degradation of ER-α and MGMT proteins by fulvestrant or O(6)-benzylguanine indicates fresh avenues for therapy. J Biomed Res. 2016 Sep;30(5):393-410. doi: 10.7555/JBR.30.20160040. Epub 2016 Jun 10. PubMed PMID: 27845303; PubMed Central PMCID: PMC5044712.

3: Vaidyanathan G, White B, Affleck DJ, McDougald D, Zalutsky MR. Radioiodinated O(6)-Benzylguanine derivatives containing an azido function. Nucl Med Biol. 2011 Jan;38(1):77-92. doi: 10.1016/j.nucmedbio.2010.07.006. Epub 2010 Oct 27. PubMed PMID: 21220131; PubMed Central PMCID: PMC3052924.

4: Penketh PG, Shyam K, Baumann RP, Ishiguro K, Patridge EV, Zhu R, Sartorelli AC. A strategy for selective O(6)-alkylguanine-DNA alkyltransferase depletion under hypoxic conditions. Chem Biol Drug Des. 2012 Aug;80(2):279-90. doi: 10.1111/j.1747-0285.2012.01401.x. Epub 2012 May 23. PubMed PMID: 22553921; PubMed Central PMCID: PMC3399964.

5: Zhu R, Liu MC, Luo MZ, Penketh PG, Baumann RP, Shyam K, Sartorelli AC. 4-nitrobenzyloxycarbonyl derivatives of O(6)-benzylguanine as hypoxia-activated prodrug inhibitors of O(6)-alkylguanine-DNA alkyltransferase (AGT), which produces resistance to agents targeting the O-6 position of DNA guanine. J Med Chem. 2011 Nov 10;54(21):7720-8. doi: 10.1021/jm201115f. Epub 2011 Oct 17. PubMed PMID: 21955333; PubMed Central PMCID: PMC3220054.

6: Liu X, Wang JQ, Zheng QH. Lipophilicity coefficients of potential tumor imaging agents, positron-labeled O(6)-benzylguanine derivatives. Biomed Chromatogr. 2005 Jun;19(5):379-84. PubMed PMID: 15651082.

7: Tomaszowski KH, Schirrmacher R, Kaina B. Multidrug Efflux Pumps Attenuate the Effect of MGMT Inhibitors. Mol Pharm. 2015 Nov 2;12(11):3924-34. doi: 10.1021/acs.molpharmaceut.5b00341. Epub 2015 Oct 1. PubMed PMID: 26379107.

8: Griffin RJ, Arris CE, Bleasdale C, Boyle FT, Calvert AH, Curtin NJ, Dalby C, Kanugula S, Lembicz NK, Newell DR, Pegg AE, Golding BT. 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. J Med Chem. 2000 Nov 2;43(22):4071-83. PubMed PMID: 11063604.

9: Sun G, Zhao L, Fan T, Ren T, Zhong R. Measurement of O(6)-alkylguanine-DNA alkyltransferase activity in tumour cells using stable isotope dilution HPLC-ESI-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Oct 15;1033-1034:138-46. doi: 10.1016/j.jchromb.2016.08.010. Epub 2016 Aug 8. PubMed PMID: 27544051.

10: Kotandeniya D, Murphy D, Yan S, Park S, Seneviratne U, Koopmeiners JS, Pegg A, Kanugula S, Kassie F, Tretyakova N. Kinetics of O(6)-pyridyloxobutyl-2'-deoxyguanosine repair by human O(6)-alkylguanine DNA alkyltransferase. Biochemistry. 2013 Jun 11;52(23):4075-88. doi: 10.1021/bi4004952. Epub 2013 May 31. PubMed PMID: 23683164; PubMed Central PMCID: PMC3750081.

11: Ishiguro K, Shyam K, Penketh PG, Sartorelli AC. Development of an O(6)-alkylguanine-DNA alkyltransferase assay based on covalent transfer of the benzyl moiety from [benzene-3H]O(6)-benzylguanine to the protein. Anal Biochem. 2008 Dec 1;383(1):44-51. doi: 10.1016/j.ab.2008.08.009. Epub 2008 Aug 20. PubMed PMID: 18783719; PubMed Central PMCID: PMC2773450.

12: Loktionova NA, Pegg AE. Interaction of mammalian O(6)-alkylguanine-DNA alkyltransferases with O(6)-benzylguanine. Biochem Pharmacol. 2002 Apr 15;63(8):1431-42. PubMed PMID: 11996884.

13: Wedge SR, Porteus JK, May BL, Newlands ES. Potentiation of temozolomide and BCNU cytotoxicity by O(6)-benzylguanine: a comparative study in vitro. Br J Cancer. 1996 Feb;73(4):482-90. PubMed PMID: 8595163; PubMed Central PMCID: PMC2074446.

14: Pegg AE, Goodtzova K, Loktionova NA, Kanugula S, Pauly GT, Moschel RC. Inactivation of human O(6)-alkylguanine-DNA alkyltransferase by modified oligodeoxyribonucleotides containing O(6)-benzylguanine. J Pharmacol Exp Ther. 2001 Mar;296(3):958-65. PubMed PMID: 11181929.

15: Alvino E, Pepponi R, Pagani E, Lacal PM, Nunziata C, Bonmassar E, D'Atri S. O(6)-benzylguanine enhances the in vitro immunotoxic activity of temozolomide on natural or antigen-dependent immunity. J Pharmacol Exp Ther. 1999 Dec;291(3):1292-300. PubMed PMID: 10565854.

16: Pauly GT, Moschel RC. Mutagenesis by O(6)-methyl-, O(6)-ethyl-, and O(6)-benzylguanine and O(4)-methylthymine in human cells: effects of O(6)-alkylguanine-DNA alkyltransferase and mismatch repair. Chem Res Toxicol. 2001 Jul;14(7):894-900. PubMed PMID: 11453737.

17: Woodside AM, Guengerich FP. Misincorporation and stalling at O(6)-methylguanine and O(6)-benzylguanine: evidence for inactive polymerase complexes. Biochemistry. 2002 Jan 22;41(3):1039-50. PubMed PMID: 11790128.

18: Tintoré M, Grijalvo S, Eritja R, Fàbrega C. Synthesis of oligonucleotides carrying fluorescently labelled O(6)-alkylguanine for measuring hAGT activity. Bioorg Med Chem Lett. 2015 Nov 15;25(22):5208-11. doi: 10.1016/j.bmcl.2015.09.065. Epub 2015 Sep 30. PubMed PMID: 26459209.

19: Sun G, Zhang N, Zhao L, Fan T, Zhang S, Zhong R. Synthesis and antitumor activity evaluation of a novel combi-nitrosourea prodrug: Designed to release a DNA cross-linking agent and an inhibitor of O(6)-alkylguanine-DNA alkyltransferase. Bioorg Med Chem. 2016 May 1;24(9):2097-107. doi: 10.1016/j.bmc.2016.03.041. Epub 2016 Mar 25. PubMed PMID: 27041398.

20: Ishiguro K, Shyam K, Penketh PG, Baumann RP, Sartorelli AC, Rutherford TJ, Ratner ES. Expression of O(6)-Methylguanine-DNA Methyltransferase Examined by Alkyl-Transfer Assays, Methylation-Specific PCR and Western Blots in Tumors and Matched Normal Tissue. J Cancer Ther. 2013 Jun;4(4):919-931. PubMed PMID: 23946891; PubMed Central PMCID: PMC3740405.