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MODULATORS OF IDO1 SIGNALING ACTIVITY AND METHODS OF USE THEREOF

Autoimmune diseasescancerImmunotherapyMultiple sclerosisType 1 Diabetes

Introduction

The invention concerns therapeutic treatments for autoimmune diseases, such as multiple sclerosis and juvenile diabetes. More in details, the invention relates to the discovery of small molecular weight compounds that bind to the IDO1 enzyme and modulate its signaling function, reprogramming immune responses towards long-term immune tolerance.

Technical features

The invention concerns the discovery of a new class of small molecules with formula I that, by direct binding of IDO1, can activate IDO1-based signalling and consequent dendritic cell-mediated control of immunity over the long period. Among studied compounds, VIS-110 was selected as preclinical candidate being the most effective in both in vitro and in vivo pharmacological experiments. When administered in a multiple sclerosis disease model in mice (experimental autoimmune encephalomyelitis or EAE), VIS-110 was found to effectively reduce disease symptoms in a dose-dependent manner. Current treatment options against multiple sclerosis do not provide long-term protection against neurodegeneration, hence compounds such as VIS-110, which attempts modulation through novel pathways, could potentially be valuable alternatives.

Possible Applications

  • Multiple sclerosis;
  • Autoimmune diseases;
  • Type 1 diabetes;
  • Oncology;
  • Co-adjuvant in current immunotherapies.

Advantages

  • First-in-class molecule mechanistically different from current drugs;
  • Oral bioavailability;
  • Cost-effective manufacturing and formulation with respect to biologics;
  • Lower side-effect risks associated to induction of immune tolerance, rather than immunosuppression.