

CSF-1R inhibitor Discovery Programme
Categories for this inventionDrug Discovery Oncology
Intellectual PropertyTRICYCLIC HETEROCYCLIC DERIVATIVES AND USES THEREOF National Phase Application
Seeking:
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SummaryAn intuitive approach of using a unique scaffold and structure based approach to synthesis highly potent CSF-1R inhibitors for cancer therapy.
Problems AddressedColony-stimulating factor 1 receptor (CSF1R), is a cell-surface receptor and plays an important role as regulator of the development, morphology, survival, and functions of tissue macrophages as well as tumor-associated macrophages (TAMs). CSF1 is involved in the recruitment and survival of macrophages in tumors. Increased CSF1 expression is implicated in tumor progression and metastasis, and is associated with poor prognosis in some cancers
TechnologyBy combining our knowledge in medicinal chemistry and biology, we have developed a novel series of highly potent and selective CSF-1R inhibitors that are currently at lead stage. We have identified a unique scaffold consisting of a tricyclic heterocyclic compound with improved selectively over competitors’ programmes. These compounds show good efficacy as a single agent but have potential in combination therapies with PD-1, PDL-1, CTLA-4 antibodies, IDO inhibitors and cancer vaccines. ApplicationsTargeting CSF-1R (c-FMS Kinase) activity has the potential to treat various pathologies and conditions such as: 1. Cancer 2. Inflammation 3. Autoimmune diseases 4. Bone disease 5. Allograft rejection 6. Arteriosclerosis and atherosclerosis Advantages• Unique scaffold which differentiates our program from competitors. • Used a structure based design approach using this scaffold docked with CSF1R structure. • Our compounds have low nM potency and high degrees of selectivity with respect to other class III kinases. • Specificity and control – reduced risk of off-target effects and increased potency. • A world-class medicinal chemistry team at Auckland Cancer Society Research Centre with experience in design and evaluation of orally-active drug candidates. • Promising results as a single agent and in combination with checkpoint inhibitors. |
InventorsProfessor Bill DennyAuckland Cancer Society Research Centre Faculty of Medical and Health Sciences Dr Jack FlanaganAuckland Cancer Society Research Centre Faculty of Medical and Health Sciences
Professor Peter ShepherdMaurice Wilkins Research Centre Faculty of Medical and Health Sciences
Questions about this Technology?Contact Dr Sandhya Badrinarayanan |