Background

  • Furin is a ubiquitous endoprotease. It is a member of the Proprotein Convertase (PC) family.1
  • While cycling between the Trans-Golgi Network and cell surface, it cleaves numerous endogenous proteins, including growth factors (TGFbeta), Receptors (Insulin receptor) and Metalloproteinases (MMP14).
  • In most cases, furin cleavage is an absolute requirement for bioactivity
  • Many groups have demonstrated that PCs have essential roles in a range of diseases.2

Furin Inhibitors & Disease

  • Many academic groups developed furin inhibitors, including proteins, peptides, small-molecules.3
  • At least one “big pharma” has developed small-molecule inhibitors.
  • Some academic research groups, biotechs and “big pharma” are developing inhibitors for use in a range of applications.
    • Atherosclerosis (PCSK9)
    • Cancer.
    • Arthritis.
    • Scarring.

Furin and Disease

  • Commercial development of furin inhibitors for use as anti-microbials has lagged. This may be to concerns about long-term treatment and/or commercial viability.
  • Furin processes numerous bacterial toxins and viral coat proteins. This is usually essential to pathogenicity.4,5
  • Examples of bacterial toxins include:
    • Bacillus anthracis Protective Antigen (PA)6
    • S. dysenteriae; E. coli O157:H7 Shiga Toxin7,8
    • Pseudomonas aeruginosa Exotoxin A.9
  • Potent efficacy has been demonstrated for Inhalation Anthrax and Pseudomonas Ocular keratitis animal models.
    • Inhalation Anthrax. Several groups have demonstrated inhibitor (Derivatized peptides, Inter—inhibitor) post-exposure efficacy in murine model. Synergy with Cipro, moxifloxacin.10,11,12,13
    • Pseudomonas Ocular keratitis. One group demonstrated inhibitor (Peptide-based) efficacy for ocular keratitis in murine model. Synergy with Cipro.14

Furin Inhibitor Intellectual Property

Related Technologies & Companies

  • Prothera Biologics Prothera Biologics. Brown Spin-out led by but Yow-Pin Lim (CEO, Professor at Brown). Developing Inter-Alpha-Inhibitor proteins for clinical use. Website suggests focus on inflammatory disease, but PI has research focus on infectious disease. Founded in 2002. Some venture funding now primarily funded by SBIRs.
  • Molecular Therapeutics. Acquired by Charles River in 2008. Was a privately held biotechnology holding company that in-licensed “promising pharmaceuticals.” Received $0.94M SBIR Phase I in 2003 for “Hexa-D-Arg: A Furin Inhibitor for Anthrax Biodefense."
  • Boise Technology. Appears to have relocated and re-focused on spectroscopic technology. Received $0.4M Phase I SBIRin 2009 for “Identification of small molecule furin-like protease inhibitors.”
  • 60° Pharmaceuticals, LLC. In 2013, Sanford-Burnham Medical Research Institute and 60° Pharmaceuticals (Washington, D.C.)announced a partnership to test furin inhibitors for the treatment of Dengue Fever. 60P’s mission is to discover, develop, and distribute drugs for neglected diseases with modest markets. It operates as a “philanthropic-for-profit” structure.
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