Cell Signaling and Cancer
From our inception, our research has focused on exploring cell-signaling pathways, identifying their role in disease, and discovering drug candidates that are specifically targeted to proteins involved in those pathways.
Many of the critical functions of cells, including cell growth, division, metabolism, motility and survival, are dependent on chemical signals carried between the cell’s surface and nucleus, and within the cell through a network of molecular signaling pathways. Alterations in these pathways underlie many disease states and in particular are the hallmarks of many types of cancer. Thanks to recent advances in cancer biology and genomics, we now understand in great detail how specific cell-signaling defects lead to particular cancers. Numerous signaling proteins that have been well-characterized and validated as drug discovery targets that can be blocked using small-molecule therapies.
Small molecule drug discovery at ARIAD
Our drug discovery program is focused on small-molecule therapies, molecularly targeted to cell-signaling proteins and pathways implicated in cancer. Our validated internal drug discovery engine builds on our expertise in cell signaling, cancer biology and structure-based drug design, that has already led to discovery and clinical development of deforolimus and AP24534.
Our discovery group is a tightly-integrated, interdisciplinary team of scientists with expertise in medicinal chemistry, structural and computational drug design, cell biology, pharmacology and drug metabolism. These groups deploy structural and computational approaches to design candidate drugs to inhibit validated molecular targets. Our aim is to rapidly identify promising lead candidates by combining computational “virtual screening” and drug design tools with innovative chemistry. We then use experimental structural biology tools, such as crystallography, along with biological, pharmacological and metabolic assays to rapidly mature these leads into drug candidates. This approach accelerates the processes of lead generation and optimization to create novel small-molecule based drug candidates.
Currently, our discovery group is focused on identifying inhibitors of protein kinases – enzymes that transfer phosphate groups between different proteins, and are key players in virtually all signaling pathways. There are over 500 kinases encoded in the human genome, many of them directly implicated in human cancer. Kinases are a rich source of validated molecular targets for small molecule drug discovery efforts, and are particularly suitable to our integrated structure-based approach to drug design.
We are currently working actively on multiple kinase oncology targets. Our goal is to nominate our next development candidate by the end of 2008.
