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Chemical Structure| 19916-73-5 Chemical Structure| 19916-73-5

Structure of O6-Benzylguanine
CAS No.: 19916-73-5

Chemical Structure| 19916-73-5

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O6-Benzylguanine is an inactivator of O6-alkylguanine DNA alkyltransferase (AGT) and can prevent the repair of DNA damage induced by chemotherapeutics. It induces apoptosis and cell death. 

Synonyms: NSC 637037; O6-BG; CCRIS 9383

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Product Details of O6-Benzylguanine

CAS No. :19916-73-5
Formula : C12H11N5O
M.W : 241.25
SMILES Code : C3=NC1=C(C(=NC(=N1)N)OCC2=CC=CC=C2)[NH]3
Synonyms :
NSC 637037; O6-BG; CCRIS 9383
MDL No. :MFCD00269931
InChI Key :KRWMERLEINMZFT-UHFFFAOYSA-N
Pubchem ID :4578

Safety of O6-Benzylguanine

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
K562 cells 0–800 µM 1 hour To evaluate the killing effect of BG and BCNU on K562 cells, results showed that K562 cells transduced with mutant MGMT exhibited stronger drug resistance. Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):4950-4.
HEK293 cells 10 µM or 50 µM 1 hour pretreatment Inhibit AGT activity, increase O6-meG-induced transcriptional mutagenesis Nucleic Acids Res. 2010 Dec;38(22):8178-87.
Human colon tumor HT29 cells 10 µM 2 hours To evaluate the enhancement of chemotherapeutic agent cytotoxicity by O6-Benzylguanine pretreatment, results showed that 10 μM O6-Benzylguanine pretreatment for 2 hours significantly enhanced the cytotoxicity of chemotherapeutic agents Proc Natl Acad Sci U S A. 1990 Jul;87(14):5368-72.
SF767 cells 10 µM 2 or 24 hours Evaluate the inhibitory effect of NPCP-BG-CTX on MGMT activity, results showed NPCP-BG-CTX significantly reduced MGMT activity after 24 hours ACS Nano. 2014 Oct 28;8(10):10383-95.
SF767 cells 20 µM 24 hours Evaluate the enhancement effect of NPCP-BG-CTX on TMZ cytotoxicity, results showed NPCP-BG-CTX significantly enhanced TMZ toxicity to SF767 cells ACS Nano. 2014 Oct 28;8(10):10383-95.
SMS-KCNR 25 µM 24 hours Enhanced TMZ cytotoxicity, increasing TMZ cytotoxicity by 0.9 logs Br J Cancer. 2010 Oct 26;103(9):1369-79.
CHLA-42 25 µM 24 hours Enhanced TMZ cytotoxicity, increasing TMZ cytotoxicity by 0.6 logs Br J Cancer. 2010 Oct 26;103(9):1369-79.
CHLA-15 25 µM 24 hours Enhanced TMZ cytotoxicity, increasing TMZ cytotoxicity by 0.3-1.4 logs Br J Cancer. 2010 Oct 26;103(9):1369-79.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
C57BL/6 mice 005 GSC-derived brain tumor model Intraperitoneal injection 0.3 mg Single dose 1 hour prior O6-BG addition to TMZ improved survival, but the combination with G47Δ-IL12 did not overcome the antagonistic effects of TMZ treatment on oHSV therapy. J Immunother Cancer. 2020 May;8(1):e000345
Mice CD-1 mice Intraperitoneal injection 10 mg/kg Single dose To evaluate the effect of O6-Benzylguanine on alkyltransferase activity in mice, results showed that 10 mg/kg O6-Benzylguanine reduced alkyltransferase levels by more than 95% in both liver and kidney within 2 hours Proc Natl Acad Sci U S A. 1990 Jul;87(14):5368-72.
Baboons and macaques Nonhuman primate models Intravenous infusion 120 mg/m² Multiple treatment cycles Stable increase in the percentage of transgene-expressing cells through O6BG and BCNU treatment, achieving multilineage selection. J Clin Invest. 2010 Jul;120(7):2345-54
Mice CD46tg mice and CD46+/+/Hbbth-3 mice Intraperitoneal injection 15 mg/kg Every 2 weeks for 3 cycles To select gene-corrected hematopoietic stem cells via O6BG/BCNU treatment, enhancing γ-globin expression levels and ameliorating the thalassemia phenotype. J Clin Invest. 2019 Feb 1;129(2):598-615
Mice CD46-transgenic mice and Hbbth3/CD46+/- thalassemic mice model Intraperitoneal injection 15 mg/kg Two injections, 30 minutes apart, followed by BCNU treatment, for a total of 4 cycles at 2-week intervals For in vivo selection of transduced hematopoietic stem cells, results showed stable GFP marking and complete correction of the thalassemia phenotype Blood Adv. 2021 Mar 9;5(5):1239-1249
Nude mice Orthotopic human primary GBM6 xenograft model Convection-enhanced delivery (CED) 15 μg/kg Twice weekly for 2 weeks Evaluate the therapeutic effect of NPCP-BG-CTX in combination with TMZ, results showed NPCP-BG-CTX/TMZ significantly extended median survival ACS Nano. 2014 Oct 28;8(10):10383-95.
Nude mice (nu/nu) Neuroblastoma xenograft models (SMS-KCNR, CHLA-136, CHLA-119) Intraperitoneal injection 30 mg/kg 5 days per week for 4 cycles (1 cycle every 3 weeks) O6-BG significantly enhanced the anti-tumour activity of TMZ in SMS-KCNR xenografts (P=0.002) and showed marginal enhancement in CHLA-119 xenografts (P=0.018). O6-BG as a single agent significantly improved survival of CHLA-136 xenografts (P=0.007). Br J Cancer. 2010 Oct 26;103(9):1369-79.
NOD/SCID mice Human hematopoietic stem cell transplantation model Intraperitoneal injection 30 mg/kg Preconditioning once, followed by two treatments at 3-week intervals Evaluate the in vivo selection effect of BG/BCNU treatment on transduced human hematopoietic stem cells, results showed after two BG/BCNU treatments, human CD45+ cells accounted for 1.9-20%, and 99% of CFUs contained MGMT(P140K) gene J Clin Invest. 2003 Nov;112(10):1561-70
Athymic MF-1 mice Subcutaneous human glioma (U87MG) xenografts Intraperitoneal injection 40 mg/kg Single dose, administered 1 h before To evaluate the enhancement of anti-tumour activity of temozolomide and BCNU by O6-BG. Results showed that O6-BG significantly enhanced the anti-tumour activity of temozolomide and BCNU (P<0.002). Br J Cancer. 1996 May;73(9):1049-52

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

4.15mL

0.83mL

0.41mL

20.73mL

4.15mL

2.07mL

41.45mL

8.29mL

4.15mL

 

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