Intercepting inflammation with RIPK2 inhibitors

Intercepting inflammation with RIPK2 inhibitors

The opportunity

  • RIPK2 is a key driver of inflammation
  • Potent and specific RIPK2 inhibitor developed
  • Established enzyme assays and models for in vitro and in vivo testing

Receptor-interacting serine/threonine kinase 2 (RIPK2) signalling drives expression of proinflammatory cytokines and type I interferon. Hyperactivation of the NOD2:RIPK2 pathway is a key driver of inflammatory bowel disease (IBD) and RIPK2 inhibitors show efficacy in preclinical models of IBD. To date, no RIPK2-specific inhibitors have advanced to clinical trials, and as such, there is a first-in-class opportunity to address these significant unmet.

Scientific diagram

 

The technology

We have developed a small molecule inhibitor of RIPK2, WEHI-345, that has potent anti-RIPK2 activity, high specificity for RIPK2 and good in vitro and in vivo efficacy. WEHI-345 demonstrated bioavailability in mice and there was no pathology or changes to white blood cells observed at the maximum tolerated.

Opportunities for partnership

We are seeking a co-development partner for our structure enabled drug discovery program to generate a potent, specific RIPK2 inhibitor.

We have:

  • a lead compound, validated enzyme assays and comprehensive in vitro and in vivo models for inhibitor validation
  • granted patent for the RIPK2 inhibition as a method of treatment for inflammatory conditions, Crohn’s Disease and other diseases
  • comprehensive expertise in lead optimisation including medicinal chemistry and structural biology

We are seeking investment to complete:

  • lead optimisation and medicinal chemistry
  • preclinical validation

Scientific team

Associate Professor Guillaume Lessene - Division Head, Chemical Biology Division

Dr Ueli Nachbur - Senior Postdoctoral Fellow, Cell Signalling and Cell Death Division

Contact

Dr David Segal, Technology Development Manager

Phone: +61 3 9345 2418 

Email: partnering@wehi.edu.au