Osteoporosis and Cathepsin K

Osteoporosis is an age-related disease characterized by the chronic and progressive loss of bone mass.  Disease progression eventually leads to structural deterioration resulting in bone fragility and an increased risk of fractures; especially of the hip, spine and wrist.  Osteoporotic fractures are also associated with disabling pain.

Cathepsin K is primarily expressed in osteoclasts (i.e. bone degrading cells) to catalyse the proteolytic processing of type I collagen as part of the natural cycle of bone remodelling.  In osteoporosis, there is an increase in type I collagen processing, leading to a weakening of the bone matrix, bone density loss, fragility and skeletal damage.  Here, the inhibition of cathepsin K activity provides a novel treatment for osteoporosis.

General information on Osteoporosis: link here

National Osteoporosis Society: link here

Search MEROPS peptidase database: link to MEROPS here

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 an in vivo study, a single oral dose of our leading cathepsin K inhibitors significantly reduced serum bone markers (sCTxI and sNTx); improving upon the profile of competitor compounds that have entered the clinic.  A significant pharmacodynamic effect is maintained for 24 hours showing a suitable profile for a once daily oral therapy.

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.