Potent, orally active inhibitor of O6-methylguanine-DNA-methyltransferase (MGMT; IC50 value 5 nM). Lomeguatrib effectively inactivated MGMT in MCF-7 cells and in xenografts there was complete inactivation of MGMT within 2 h of dosing (20 mg/kg i.p.) and only slight recovery by 24 h.Oral administration of Lomeguatrib substantially increases the haematological toxicity of Dacarbazine, the only approved chemotherapeutic agent for the treatment of metastatic melanoma. In combination with Temozolomide, Lomeguatrib produced a substantial tumour growth delay in MCF-7 xenografts.