Dipeptidyl peptidase I (cathepsin C)

- a novel target for the treatment of inflammatory diseases


UNIZYME Laboratories is a virtual Danish biotech company focused on design and development of novel small molecule inhibitors of dipeptidyl peptidase I (DPPI; also known as cathepsin C) for treatment of inflammatory diseases.


For a number of inflammatory diseases, DPPI activated neutrophil and mast cell-derived serine proteases (e.g. elastase, cathepsin G, tryptase, etc.) are part of disease progression and studies in DPPI knockout mice have linked activity of DPPI to a range of inflammatory diseases, including COPD, Asthma, Rheumatoid Arthritis, Myocardial Infarction/Heart Failure, Diabetic Cardiomyopathy and Sepsis. Other studies indicate that inhibition of DPPI also represent a therapeutic strategy for treating additional inflammatory diseases, such as Psoriasis, Multiple Sclerosis and Inflammatory Bowel Disease.


Unizyme has demonstrated the feasibility of using a proprietary DPPI inhibitor for reducing disease severity in an animal model of an inflammatory disease (Collagen Antibody-induced arthritis model)


Unizyme have several compounds (covered by patent applications) that satisfy many of the criteria for a future drug candidate, including


  • high potency in both enzyme- and cell-based assays (IC50 < 10 nM)
  • reversible properties
  • an appropriate chemical and metabolic stability
  • absence of obvious toxic chemical structures
  • nonproblematic synthesis with potential for scale-up
  • logP less than 5
  • excellent cell permeability
  • absence of cell cytotoxicity and obvious toxicity
  • selectivity over CYP enzymes and hERG
  • an excellent PK-profile leading to high and sustained concentration of inhibitor at the site of drug action
    (i.e. bone marrow)
  • effectiveness in an inflammatory disease model


Based on the above we feel convinced that we have at least two lead compounds (as representative of two different compound series) with potential to progress to a full drug development programme.


Unizyme has more than 20 years of experience with DPPI and more than 10 years of experience in the DPPI inhibitors field. Unizyme has extensive know-how and owns strategically important IP rights covering reversible covalent DPPI inhibitors and structure based drug design of DPPI inhibitors using the DPPI crystal structure.



Unizyme is looking for a qualified and dedicated partner to accelerate the further development of its DPPI inhibitor program. Contact: John Pedersen.


July 2012