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.
Amura has licensing opportunities for its AMcore™-based programmes.