MGMT inhibitor Lomeguatrib Small Molecule (Tool Compound)
Invented at Cancer Research UK Manchester Institute
- Datasheet
- References (8)
- Inventor Info
Info
| Catalogue Number | 151711 |
| Antigen/Gene or Protein Targets | DNA repair protein MGMT and related mammalian proteins |
| Synonyms | PaTrin 2 |
| Type | Inhibitor |
| Relevance | 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. |
| On Target IC50 | 5 nM |
| Molecular Formula | C10H8BrN5OS |
| lUPAC | 2-Amino-6-[(4-bromo-2-thienyl)methoxy]-9H-purine |
| Molecular Weight (g/mol) | 326.17 |
| In vivo applications | 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. |
| In vitro applications | 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 μM ) substantially increases the growth inhibitory effects of temozolomide in MCF-7 cells (D60= 10 μM with Lomeguatrib vs 400 μM without). |
| Research Area | DNA Damage and Repair, Epigenetics & Nuclear Signalling |
| Storage | Ambient |
References: 8 entries
Watson et al. 2010. Clin Cancer Res. 16(2):743-9. PMID: 20068091.
Tumor O(6)-methylguanine-DNA methyltransferase inactivation by oral lomeguatrib.
Europe PMC ID: 20068091
Khan et al. 2008. Br J Cancer. 98(10):1614-8. PMID: 18475294.
A phase II trial of lomeguatrib and temozolomide in metastatic colorectal cancer.
Europe PMC ID: 18475294
Ranson et al. 2006. Clin Cancer Res. 12(5):1577-84. PMID: 16533784.
Lomeguatrib, a potent inhibitor of O6-alkylguanine-DNA-alkyltransferase: phase I safety, pharmacodynamic, and pharmacokinetic trial and evaluation in combination with temozolomide in patients with advanced solid tumors.
Europe PMC ID: 16533784
Clemons et al. 2005. Br J Cancer. 93(10):1152-6. PMID: 16278661.
O6-(4-bromothenyl)guanine reverses temozolomide resistance in human breast tumour MCF-7 cells and xenografts.
Europe PMC ID: 16278661
Add a reference
References: 8 entries
Watson et al. 2010. Clin Cancer Res. 16(2):743-9. PMID: 20068091.
Tumor O(6)-methylguanine-DNA methyltransferase inactivation by oral lomeguatrib.
Khan et al. 2008. Br J Cancer. 98(10):1614-8. PMID: 18475294.
A phase II trial of lomeguatrib and temozolomide in metastatic colorectal cancer.
Ranson et al. 2006. Clin Cancer Res. 12(5):1577-84. PMID: 16533784.
Lomeguatrib, a potent inhibitor of O6-alkylguanine-DNA-alkyltransferase: phase I safety, pharmacodynamic, and pharmacokinetic trial and evaluation in combination with temozolomide in patients with advanced solid tumors.
Clemons et al. 2005. Br J Cancer. 93(10):1152-6. PMID: 16278661.
O6-(4-bromothenyl)guanine reverses temozolomide resistance in human breast tumour MCF-7 cells and xenografts.
Add a reference
