As important regulators of both genomic integrity and cell cycle progression in cancer cells the Aurora kinases represent an attractive target for anticancer drug development.
Aurora kinases are enzymes that help dividing cells share their materials between two daughter cells. In many people with cancer Aurora kinase malfunctions and normal control of cell division is lost resulting in abnormal growth.
Small molecule drugs that inhibit Aurora kinase may slow down the growth of cancer cells and lead to their death by apoptosis.
Cyclacel's small molecule investigational drug, CYC116, is the third orally-available Cyclacel drug to enter development, which demonstrated anticancer activity with a mechanism consistent with inhibition of Aurora kinase.
The company plans to file an Investigational New Drug (IND) application for CYC116 with the United States Food and Drug Administration (FDA) in 2006.
"Together with seliciclib and sapacitabine, our two clinical development candidates, advancement of CYC116 demonstrates our strategy of building a novel oncology-focused pipeline of drugs acting on the cancer cell cycle," said Cyclacel's CEO, Spiro Rombotis.
The company is currently evaluating seliciclib (CYC202), an orally-available Cyclin Dependent Kinase inhibitor, in Phase II clinical trials for the treatment of non-small cell lung cancer and B-cell hematological malignancies.
Sapacitabine (CYC682) is an orally available, cell cycle modulating nucleoside analog in Phase I clinical trials for the treatment of cancer.
Proof of the Aurora kinase's potential was demonstrated back in June with Merck & Co's decision to invest up to $350 million (€288m) in a license for the lead compound in the class.
Aurora kinases are overexpressed in various tumour types such as leukaemia and colon and breast cancer, and are thought to play multiple roles in the development of cancer.
In addition to acting as regulators of cell proliferation, they have been shown to convert normal cells to cancer cells and inhibiting p53, a natural tumour suppressor protein.
One other company working in this area is AstraZeneca, which presented preclinical data on one of its Aurora kinase inhibitors, AZD1152, at the American Association of Cancer Research meeting earlier this year.