Drug Discovery - Other Programmes (PLK, B-raf, FASN)

Polo-like Kinase (PLK)

Higher levels of PLK-1 protein have been shown to be present in many types of cancer including non-small-cell lung cancer, head and neck cancer, esophageal cancer, gastric cancer, melanomas, breast cancer, ovarian cancer, endometrial cancer, colorectal cancer, gliomas, and thyroid cancer. These higher PLK-1 levels have been linked to patients with a poor disease prognosis. In addition, reducing PLK-1 enzyme activity or protein levels has been shown to induce tumour cell death in a variety of biological model systems. The normal cellular role of PLK-1 is as a critical regulator of cell division during mitosis and interfering with this process has been shown to lead to the programmed cell death (apoptosis) of tumour cells.

Sareum have identified a variety of novel small molecule PLK-1 inhibitors and are seeking a partner to fund the optimisation into drug candidates.

B-raf

Many cancers have been shown to have mutations in the B-raf gene which cause a large increase in the enzyme activity of the B-raf protein kinase. These mutations have been observed in over 60% of malignant melanoma as well as colorectal, thyroid, cholangiocarcinoma, lung adenocarcinoma and glioblastoma. In addition, introduction of these mutant forms of B-raf into experimental models have reproduced and sustained tumourigenesis.

Sareum have inuitiated a discovery programme to produce inhibitors that reduce B-raf enzyme activity. Such small molecular weight inhibitors, in appropriate cancer patients, would be expected to reverse the harmful effects of cellular transformation and even lead to tumour eradication in combination with other existing therapies.

Fatty Acid Synthase (FASN)

FASN over-expression is one of the most common changes in cancer cells.

We have developed a novel chemical series which is effective in breast cancer cell models.

We are seeking a collaboration partner to fund the further development of these compounds.