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Novel class of therapeutics for treatment of lupus and other autoimmune and inflammatory conditions


First in class compounds inhibiting BRISC deubiquitinating enzymes for treatment of autoimmune diseases.



Lupus is an autoimmune disease affecting approximately 5 million people worldwide. Lupus results in a hyperactive immune system and multisystem pathologic changes to joints, skin, kidneys, blood cells, and lungs. Immunosuppressive drugs are the current standard of care for lupus patients, but have unfavorable side effects and limitations leaving a need for alternative treatment methods.



A majority of individuals with lupus display elevated expression of type-1 interferon (IFN) inducible genes in circulating immune cells and peripheral tissues, which correlates with disease severity. Dr. Roger Greenberg has discovered that BRISC deubiquitinating enzymes play a critical role in IFN and other inflammatory cytokine responses and showed that BRISC deficiency in mice reduces activation of immune cells and ameliorates lupus.


Dr. Greenberg’s team includes a medicinal chemist, structural biologist, and molecular biologist. They have reported the structural basis of BRISC activation and developed the first high throughput screen for small molecule BRISC inhibitors. They have obtained several potent and specific lead BRISC inhibitors and are optimizing them using medicinal chemistry and rational drug design approaches. This novel class of therapeutics present potential utility in treatment of lupus as well as other autoimmune and inflammatory conditions driven by elevated cytokine responses.







Treatment of lupus and other autoimmune and inflammatory diseases


Stage of Development:

  • Lead BRISC inhibitors with IC50~1.5μM
  • Several series of compound analogs



  • First in class therapeutics
  • Numerous drug analogs undergoing further optimization
  • BRISC knockout and enzymatically inactive knock-in mouse models
  • Structural biology of BRISC in active and inactive states
  • Novel high throughput screening technology for BRISC inhibitors

Intellectual Property:

Pending provisional application


Reference Media:

  • Zheng et al. Cell Rep, 5(1): 180-93, 2013
  • Zeqiraj et al. Mol cell, 59(6): 970-83, 2015.  

Desired Partnerships:

  • License
  • Co-development


Docket # 16-7774



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Patent Information:
For Information, Contact:
Linara Axanova
Associate Director, PSOM Licensing Group
University of Pennsylvania
Roger Greenberg