Drug Discovery – Aurora+FLT3 Kinase, Aurora+ALK Kinase

Aurora Kinases

Aurora kinases A and B are required for cells to both enter and proceed through mitosis, which is the process by which copies of the duplicated DNA chromosomes are segregated into two daughter cells. Moreover, Aurora kinases are over-expressed in a variety of cancers including pancreatic, ovarian, colon, breast, liver, lung, thyroid and bladder cancer. These cellular proteins therefore represent attractive targets for treating a wide range of cancers.

FLT3 Kinase

Fms-Like Tyrosine Kinase 3 (FLT3) is highly expressed in most acute leukaemias. Its ligand, FLT3-L, stimulates the proliferation of hematopoietic stem progenitor and dendritic cells. FLT-3 is expressed at high levels in acute myeloid leukaemia (AML) and acute lymphocytic leukaemia (ALL). FLT-3/ITD (internal tandem duplication) mutation occurs in 15% to 35% of AML patients and promotes constitutive activation of the FLT-3 receptor. AML patients carrying the ITD mutations are found to have a decreased overall survival compared with patients without ITD mutations. Inhibition of FLT3 is therefore expected to be an effective strategy for the treatment of AML and potentially other leukaemias.

ALK Kinase

Anaplastic Lymphoma Kinase (ALK) is over-activated and oncogenic in the non-Hodgkin’s lymphoma (NHL) Anaplastic Large Cell Lymphoma (ALCL) as well as certain lung cancers and childhood neuroblastomas.

More information about these programmes can be found here: Aurora+FLT3&ALK (download pdf)