ICR/Cyclacel scientists discover new cancer drug

Researchers say they have discovered a new cancer drug with potential use against a range of cancers, including some blood cancers and solid tumours.

Fadraciclib, which was jointly discovered by scientists at The Institute of Cancer Research (ICR), London, in collaboration with the company Cyclacel, is already being tested in early clinical trials targeting select haematological malignancies and solid tumours.

The drug is a dual inhibitor of two cancer-driving proteins from the cyclin-dependent kinase (CDK) family, CDK2 and CDK9.

Scientists say it was designed by improving the chemical properties of a previous CDK inhibitor drug from Cyclacel, called seliciclib, which led to a 20-fold more potent activity against the CDK2 and CDK9 targets and an equivalent 30-fold increase in therapeutic potency against a panel of human cancer cells, as well as a high degree of selectivity versus a wide range of 256 other protein kinases.

Research shows that CDK2 and CDK9 are inhibited in fadraciclib-treated cancer cells, leading to altered gene expression and cell death by apoptosis.

Experiments in cells and mice demonstrate the drug's potential as a treatment for leukaemia, the team having found that the drug inhibited the growth of human acute myeloid leukaemia tumours growing in immune-deprived mice by up to 100%.

Furthermore, the researchers observed that in cancer cells treated with fadraciclib there was a “profound and sustained decrease” in the levels of MCL1 – a protein involved in cancer cell survival and drug resistance.

“It’s exciting to reach the stage where we can reveal for the first time the chemical structure and synthesis of fadraciclib and also describe its therapeutic properties, especially in cell and mouse models of human leukaemia,” commented study co-author Professor Paul Workman, chief executive at The ICR.

“These new results are part of the successful programme of research with our partners at Cyclacel to discover and develop dual CDK2/9 inhibitors for cancer treatment. It details research that has already led to clinical trials of fadraciclib in various cancer types, and we hope will result in new targeted treatments for patients with leukaemias and solid cancers.”