O6-Benzylguanine

Names

[ CAS No. ]:
19916-73-5

[ Name ]:
O6-Benzylguanine

[Synonym ]:
O(6)-Benzylguanine
7H-purin-2-amine, 6-(phenylmethoxy)-
O6-Benzylguanine
2-amino-6-(phenylmethoxy)-9H-purine
O(6)-bGua
2-Amino-6-benzyloxy-9H-purine
O-6-Benzylguanine
6-Benzyloxy guanine
6-(Benzyloxy)-3H-purin-2-amine
2-Amino-6-(benzyloxy)purine
6-O-Benzylguanine
9H-Purin-2-amine, 6-(phenylmethoxy)-
6-(benzyloxy)guanine
O-Benzylguanine
6-(phenylmethoxy)-9H-purin-2-amine
MFCD00269931
amino-6-(phenylmethoxy)-9H-purine
6-(Benzyloxy)-7H-purin-2-amine

Biological Activity

[Description]:

O6-Benzylguanine, a guanine analog, is the DNA repair enzyme O6-alkylguanine-DNA alkyltransferase (MGMT/AGT) inhibitor. O6-Benzylguanine acts as an AGT substrate, which transfers its benzyl group to the AGT cysteine residue, thereby irreversibly inactivating AGT and preventing DNA repair. O6-Benzylguanine induces tumor cell apoptosis. Antineoplastic activity[1][2].

[Related Catalog]:

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> DNA/RNA Synthesis

[In Vitro]

The L3.6pl cells are relatively sensitive to O6-Benzylguanine (24-72 hours) in a dose- and time-dependent manner. The IC50 is 50 μg (at 48 hours)[2]. O6-Benzylguanine (50 μg; 48 hours) modulates p53 downstream target protein expression, induces apoptosis, and decreases cell proliferation[2]. O6-Benzylguanine (50 μg; 48 hours) significantly decreases the MGMT transcriptional activity in L3.6pl[2]. Western Blot Analysis[2] Cell Line: L3.6pl and PANC1 cells Concentration: 50 μg Incubation Time: 48 hours Result: Expressions of O6 methyl guanine DNA methyl transferase (MGMT), cyclin B1, cyclin B2, cyclin A, p53, and ki-67 were decreased, whereas p21 was increased. The levels of cyto C and caspase 9 were increased, whereas the levels of PARP1 protein were decreased. RT-PCR[2] Cell Line: L3.6pl cells Concentration: 50 μg Incubation Time: 48 hours Result: Decreased the MGMT transcriptional activity in L3.6pl.

[In Vivo]

O6-Benzylguanine (100 μg; i.p.; daily for 35 days) inhibits pancreatic cancer cell growth and increases pancreatic cell sensitivity to Gemcitabine (100 mg/kg)[2]. O6-Benzylguanine inhibits pancreatic cancer cell proliferation and induces tumor cell apoptosis in vivo[2]. Animal Model: Male athymic nude mice (NCI-nu) (bearing human pancreatic cancer L3.6pl cells)[2] Dosage: 100 μg Administration: i.p; daily for 35 days Result: Significantly decreased median tumor volume and weight.

[References]

[1]. Rabik CA, Njoku MC, Dolan ME. Inactivation of O6-alkylguanine DNA alkyltransferase as a means to enhance chemotherapy. Cancer Treat Rev. 2006;32(4):261‐276.

[2]. Konduri, Santhi D et al. Blockade of MGMT expression by O6 benzyl guanine leads to inhibition of pancreatic cancer growth and induction of apoptosis. Clinical cancer research : an official journal of the American Association for Cancer Research vol. 15,19 (2009): 6087-95.

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
621.4±63.0 °C at 760 mmHg

[ Melting Point ]:
193(dec.)

[ Molecular Formula ]:
C₁₂H₁₁N₅O

[ Molecular Weight ]:
241.249

[ Flash Point ]:
329.6±33.7 °C

[ Exact Mass ]:
241.096359

[ PSA ]:
89.71000

[ LogP ]:
1.95

[ Vapour Pressure ]:
0.0±1.8 mmHg at 25°C

[ Index of Refraction ]:
1.743

[ Storage condition ]:
-20°C Freezer

[ Water Solubility ]:
methanol: 20 mg/mL

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H315-H319-H335

[ Precautionary Statements ]:
P261-P305 + P351 + P338

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves

[ Hazard Codes ]:
Xi:Irritant;

[ Risk Phrases ]:
R36/37/38

[ Safety Phrases ]:
S26-S36

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ HS Code ]:
2933990090

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2933990090

[ Summary ]:
2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Articles

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Related Compounds

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