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Contributor Information

  • Name Geoffrey Margison
  • Institute Cancer Research UK, Manchester Institute

Tool Details

  • Tool name: MGMT inhibitor Lomeguatrib Small Molecule (Tool Compound)
  • Alternate names: PaTrin 2
  • Molecular formula: C10H8BrN5OS
  • Tool type: Small molecules
  • Tool sub-type: Inhibitor
  • Purpose: Inhibitor
  • Molecular weight of the target: 326.17
  • Application: 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. 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. 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. 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. Lomeguatrib effectively inactivates MGMT in MCF-7 cells with IC50 of ~6nM. Lomeguatrib (10 ÎźM ) substantially increases the growth inhibitory effects of temozolomide in MCF-7 cells (D60= 10 ÎźM with Lomeguatrib vs 400 ÎźM without).
  • Description: The MGMT inhibitor Lomeguatrib is a potent inhibitor of O6-alklguanine-DNA-alkyltransferase. It shows antitumoral activity in vivo in combination with the compound Temozolomide.
  • Research area: Cell Signaling & Signal Transduction
  • IUPAC: 2-Amino-6-[(4-bromo-2-thienyl)methoxy]-9H-purine
  • IC50: 5 nM

  • For Research Use Only

Target Details

  • Target molecular weight: 326.17
  • Primary target: DNA repair protein MGMT and related mammalian proteins

Application Details

  • Application: 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. 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. 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. 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. Lomeguatrib effectively inactivates MGMT in MCF-7 cells with IC50 of ~6nM. Lomeguatrib (10 ÎźM ) substantially increases the growth inhibitory effects of temozolomide in MCF-7 cells (D60= 10 ÎźM with Lomeguatrib vs 400 ÎźM without).

Handling

  • Purity: 326.17 g/mol
  • Storage conditions: Ambient
  • Shipping conditions: Dry Ice

Documentation

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  • Available on request

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References

  • •  Barvaux et al. 2004. Mol Cancer Ther. 3: 1215-20 (PMID: 15426188) Clemons et al. 2005. Br J Cancer. 93: 1152-6 (PMID: 16278661) Ranson et al. 2006. Clin Cancer Res. 12: 1577-84 (PMID: 16533784) Khan et al. 2008 Br J Cancer. 98: 1614-8 (PMID: 18475294) Watson et al. 2010. Clin Cancer Res. 16: 743-9 (20068091)