IRAK1/4 Inhibitor

Rigel’s investigational candidate, R835, is an orally bioavailable, potent and selective inhibitor of interleukin receptor associated kinases 1 and 4 (IRAK1/4).

R835 blocks inflammatory cytokine production in response to toll-like receptor (TLR) and interleukin-1 receptor family (IL-1R) signaling. TLRs and IL-1Rs play a critical role in the innate immune response. Therefore, dysregulation of the TLR and IL-1R pathways may be associated with a variety of inflammatory conditions including psoriasis, rheumatoid arthritis, lupus and gout (among others).

Through inhibition of TLR and IL1R signaling, R835 blocks both IL-23 production and TH17 cell differentiation providing a strong rationale for its potential use in the treatment of IL23/IL17-mediated diseases.

Development of R835:

  • In a Phase 1 clinical trial, R835 established proof-of-mechanism by demonstrating the inhibition of inflammatory cytokine production in response to toll-like receptor 4 (TLR4) signaling in an intravenous LPS challenge study.