Lomeguatrib

• CAT Number: I002464
• CAS Number: 192441-08-0
• Molecular Formula: C₁₀H₈BrN₅OS
• Molecular Weight: 326.17
• Purity: ≥95%
• Target: DNA Methyltransferase
• Solubility: DMSO: ≥ 56 mg/mL
• Storage: 2-8°C
• IC50: 6 nM
• IUPAC Name: 6-[(4-bromothiophen-2-yl)methoxy]-7H-purin-2-amine
• InChI: InChI=1S/C10H8BrN5OS/c11-5-1-6(18-3-5)2-17-9-7-8(14-4-13-7)15-10(12)16-9/h1,3-4H,2H2,(H3,12,13,14,15,16)
• InChIKey: JUJPKFNFCWJBCX-UHFFFAOYSA-N
• SMILES: C1=C(SC=C1Br)COC2=NC(=NC3=C2NC=N3)N

Lomeguatrib（Cat No.:I002464）, also known as PaTrin-2, is a potent inhibitor of O6-alkylguanine-DNA alkyltransferase (AGT). It effectively inhibits the activity of AGT, an enzyme involved in DNA repair, with an IC50 (half maximal inhibitory concentration) of 5 nM. By inhibiting AGT, lomeguatrib prevents the repair of DNA lesions induced by alkylating agents. This mechanism of action enhances the efficacy of alkylating chemotherapeutic drugs that rely on DNA damage for their anticancer effects.

Reference

1:Chemotherapeutic resistance in anaplastic astrocytoma cell lines treated with a temozolomide-lomeguatrib combination. Ugur HC, Taspinar M, Ilgaz S, Sert F, Canpinar H, Rey JA, Castresana JS, Sunguroglu A.Mol Biol Rep. 2014 Feb;41(2):697-703. doi: 10.1007/s11033-013-2908-5. Epub 2013 Dec 25. PMID: 24368590 2:Effect of lomeguatrib-temozolomide combination on MGMT promoter methylation and expression in primary glioblastoma tumor cells. Taspinar M, Ilgaz S, Ozdemir M, Ozkan T, Oztuna D, Canpinar H, Rey JA, Sunguroğlu A, Castresana JS, Ugur HC.Tumour Biol. 2013 Jun;34(3):1935-47. doi: 10.1007/s13277-013-0738-7. Epub 2013 Mar 22. PMID: 23519841 3:Inhibition of DNA repair with MGMT pseudosubstrates: phase I study of lomeguatrib in combination with dacarbazine in patients with advanced melanoma and other solid tumours. Tawbi HA, Villaruz L, Tarhini A, Moschos S, Sulecki M, Viverette F, Shipe-Spotloe J, Radkowski R, Kirkwood JM.Br J Cancer. 2011 Sep 6;105(6):773-7. doi: 10.1038/bjc.2011.285. Epub 2011 Aug 2. PMID: 21811257 Free PMC Article4:Tumor O(6)-methylguanine-DNA methyltransferase inactivation by oral lomeguatrib. Watson AJ, Sabharwal A, Thorncroft M, McGown G, Kerr R, Bojanic S, Soonawalla Z, King A, Miller A, Waller S, Leung H, Margison GP, Middleton MR.Clin Cancer Res. 2010 Jan 15;16(2):743-9. doi: 10.1158/1078-0432.CCR-09-1389. Epub 2010 Jan 12. PMID: 20068091 Free PMC Article5:A phase I trial of lomeguatrib and irinotecan in metastatic colorectal cancer. Sabharwal A, Corrie PG, Midgley RS, Palmer C, Brady J, Mortimer P, Watson AJ, Margison GP, Middleton MR.Cancer Chemother Pharmacol. 2010 Oct;66(5):829-35. doi: 10.1007/s00280-009-1225-0. Epub 2009 Dec 29. PMID: 20039040 6:O(6)-methylguanine-DNA methyltransferase depletion and DNA damage in patients with melanoma treated with temozolomide alone or with lomeguatrib. Watson AJ, Middleton MR, McGown G, Thorncroft M, Ranson M, Hersey P, McArthur G, Davis ID, Thomson D, Beith J, Haydon A, Kefford R, Lorigan P, Mortimer P, Sabharwal A, Hayward O, Margison GP.Br J Cancer. 2009 Apr 21;100(8):1250-6. doi: 10.1038/sj.bjc.6605015. PMID: 19367283 Free PMC Article7:A phase I study of extended dosing with lomeguatrib with temozolomide in patients with advanced melanoma. Kefford RF, Thomas NP, Corrie PG, Palmer C, Abdi E, Kotasek D, Beith J, Ranson M, Mortimer P, Watson AJ, Margison GP, Middleton MR.Br J Cancer. 2009 Apr 21;100(8):1245-9. doi: 10.1038/sj.bjc.6605016. Epub 2009 Mar 31. PMID: 19367282 Free PMC Article8:A phase II trial of lomeguatrib and temozolomide in metastatic colorectal cancer. Khan OA, Ranson M, Michael M, Olver I, Levitt NC, Mortimer P, Watson AJ, Margison GP, Midgley R, Middleton MR.Br J Cancer. 2008 May 20;98(10):1614-8. doi: 10.1038/sj.bjc.6604366. Epub 2008 May 13. Erratum in: Br J Cancer. 2009 Aug 4;101(3):550. PMID: 18475294 Free PMC Article9:Randomized trial of the combination of lomeguatrib and temozolomide compared with temozolomide alone in chemotherapy naive patients with metastatic cutaneous melanoma. Ranson M, Hersey P, Thompson D, Beith J, McArthur GA, Haydon A, Davis ID, Kefford RF, Mortimer P, Harris PA, Baka S, Seebaran A, Sabharwal A, Watson AJ, Margison GP, Middleton MR.J Clin Oncol. 2007 Jun 20;25(18):2540-5. PMID: 17577032 10:Novel role of triazenes in haematological malignancies: pilot study of Temozolomide, Lomeguatrib and IL-2 in the chemo-immunotherapy of acute leukaemia. Caporaso P, Turriziani M, Venditti A, Marchesi F, Buccisano F, Tirindelli MC, Alvino E, Garbin A, Tortorelli G, Toppo L, Bonmassar E, D/’Atri S, Amadori S.DNA Repair (Amst). 2007 Aug 1;6(8):1179-86. Epub 2007 May 17. PMID: 17500047