| Description |
Lomeguatrib is a potent inhibitor of O6-alkylguanine-DNA-alkyltransferase with IC50 of 5 nM. |
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Targets
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| O6-alkylguanine-DNA-alkyltransferas [1] |
| 5 nM |
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| In vitro |
Lomeguatrib inactivates O6-alkylguanine-DNA-alkyltransferase (ATase) with a IC50 10-fold lower than O6-Benzylguanine. Lomeguatrib inhibits the activity of ATase in Raji cells with IC50 of 10 nM. [1]
Lomeguatrib effectively inactivates MGMT in MCF-7 cells with IC50 of ~6nM ). Lomeguatrib (10 μM ) substantially increases the growth inhibitory effects of temozolomide in MCF-7 cells (D60= 10 μM with Lomeguatrib vs 400 μM without). [2]
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| In vivo |
Lomeguatrib (20 mg/kg/day for 5 days) combined with temozolomide (100 mg/kg/day for 5 days) produces a substantial tumour growth delay: median tumour quintupling time is increased by 22 days without any significant increase in toxicity, while neither of the two drugs administrated along show any antitumor activity. [2]
Lomeguatrib inactivates ATase and enhances the anti-tumour effect of temozolomide in A375M human melanoma xenografts model. Lomeguatrib, at a single dose of 20 mg/kg i.p., produces complete ATase depletion in tumor within 2 hr. Temozolomide (100 g/kg/day) significantly delays growth of the A375M tumour xenograft with an estimated delay in the time for tumour to quintuple in size of 9.6 days. Addition of Lomeguatrib to temozolomide significantly enhances the latter’s effect, delaying the quintupling time a further 8.7 days. Moreover, the Lomeguatrib combination results in considerably less toxicity (0/9 vs. 2/9 deaths; 6.84% weight loss vs. 9.48%). Lomeguatrib alone has no significant effect on tumour growth. [3]
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COA
HPLC