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Bone Metastasis and Cathepsin K

Metastasis is the spread of cancer cells from one site to another, resulting in the formation of secondary or metastatic tumours.  For example, when breast cancer cells spread (metastasize) to the bone, the resulting secondary tumour(s) would be referred to as metastatic breast cancer of the bone.  In the case of breast cancer metastasis, seventy percent of cancer cells migrate to the bone, forming tumours at multiple sites.  These secondary tumours are often aggressive and produce significant pain and severe osteolytic bone lesions.

General information on metastasis: link here

General information on breast cancer: link here

Primary breast cancer cells, metastatic breast cancer cells and in vitro cultured breast cancer cells have all been shown to produce significant amounts of cathepsin K (Littlewood-Evans, et al., (1997)); cathepsin K expression has also been reported to be an indicator of metastasis (Husmann, et al., (2008)).  Inhibition of cathepsin K has been shown to reduce breast cancer-induced osteolysis and skeletal tumour burden (Le Gall, et al., (2007). Inhibition of cathepsin K activity may provide a novel treatment for bone metastasis.

Amura has developed low nanomolar inhibitors of cathepsin K with excellent selectivity against other cathepsins and attractive drug-like properties, with AM-3701 identified as the development candidate. In a human breast cancer cell-induced in vivo model of bone metastasis, oral dosing of our inhibitor demonstrated a significant reduction in lesion size and total tumour burden associated with metastasis compared to the control group.

           

In addition to this in vivo PoC data, the quality of the molecules is confirmed by a comprehensive pre-clinical package which includes pharmacokinetic data, selectivity and safety assessment. The lead molecule and a first rate back-up molecule are now available for partnering.

These drugs are the product of Amura’s AMcore™ platform which  has reproducibly provided ‘fast-on, slow-off rate’ enzyme inhibitors with good pharmacokinetic half-lives and a very strong IP position. 

Full Compound Information Summaries are available under Confidentiality Agreement. 

Amura has licensing opportunities for its AMcore-based programmes.

 

 
     
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