用于各种DNA修复机制研究。

O6-Benzylguanine 是鸟嘌呤类似物，是 DNA 修复酶 O6 烷基鸟嘌呤DNA烷基转移酶 (MGMT/AGT) 抑制剂。

TargetValue AGT ()

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

The L3.6pl cells are relatively sensitive to O6-Benzylguanine (24-72 hours) in a dose- and time-dependent manner. The IC 50 is 50 μg (at 48 hours). O6-Benzylguanine (50 μg; 48 hours) modulates p53 downstream target protein expression, induces apoptosis, and decreases cell proliferation. O6-Benzylguanine (50 μg; 48 hours) significantly decreases the MGMT transcriptional activity in L3.6pl. Western Blot Analysis 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 Cell Line: L3.6pl cells Concentration: 50 μg Incubation Time: 48 hours Result: Decreased the MGMT transcriptional activity in L3.6pl.

O6-Benzylguanine 作为 AGT 底物，将其苄基转移到 AGT 半胱氨酸残基上，从而不可逆地灭活 AGT 并阻止 DNA 修复。O6-Benzylguanine 诱导肿瘤细胞凋亡，具有抗肿瘤活性。