The LOR-500 program aims to discover and develop potent, first-in-class small molecule inhibitors of maternal embryonic leucine zipper kinase (MELK). MELK plays an important role in cancer cell cycle, signaling pathways, and stem cells. MELK is highly expressed in several cancer types and its expression correlates with poor prognosis in glioma and breast cancer. These findings provide strong support that selective targeting of MELK may be an effective cancer treatment strategy. Several compounds targeting MELK have been identified and a lead drug candidate will be ready for preclinical evaluation within 3-4 months.
Breast cancer and malignant glioma have been identified as highly relevant potential indications. Breast cancer is the most common cancer in women and in the US, about 230,000 women are diagnosed with invasive breast cancer each year. Despite improvements in earlier detection and advances in the treatment, breast cancer still claim the lives of around 40,000 women in the US each year. Glioblastoma multiforme (GBM) is the most lethal primary cancer of the central nervous system, with patient survival after 5 years being less than 5%. Cancer associated kinases as drug targets are a very active area for R&D globally and kinase inhibitors are some of the best selling drugs in oncology with Imatinib, Sunitinib, Sorafenib and Erlotinib whose annual global sales amount to billions. Much of the current focus is on the development of selective kinase inhibitors that hit specific targets in cancer cells and cause less toxicity associated with off-target effect. There are no known selective inhibitors reported for MELK and Lorus believes that the LOR-500 program will produce the first selective MELK inhibitor in development for cancer treatment.