In vitro activity: PF-06700841 tosylate is a potent, selective, and conformationally constrained piperazinyl-pyrimidine Type 1 ATP site inhibitor of TYK2 and JAK1 kinases with IC50 values of 23 nM and 17 nM respectively. PF-06700841 is in Phase II clinical development (NCT02969018, NCT02958865, NCT03395184, and NCT02974868) as a potential therapeutic for the treatment of systemic lupus erythematosus and plaque psoriasis. Cytokine signaling is an important characteristic of autoimmune diseases. Many pro-inflammatory cytokines signal through the Janus kinase (JAK)/Signal transducer and activator of transcription (STAT) pathway. JAK1 is important for the γ-common chain cytokines, interleukin (IL)-6, and type-I interferon (IFN) family, while TYK2 in addition to type-I IFN signaling also plays a role in IL-23 and IL-12 signaling. Intervention with monoclonal antibodies (mAbs) or JAK1 inhibitors has demonstrated efficacy in Phase III psoriasis, psoriatic arthritis, inflammatory bowel disease, and rheumatoid arthritis studies. PF-06700841was safe and well tolerated up to 200 mg once daily in healthy subjects and 100 mg once daily in patients with psoriasis, suggesting potential therapeutic utility in plaque psoriasis and other inflammatory diseases.

Kinase Assay: PF-06700841 tosylate is a potent, selective, and conformationally constrained piperazinyl-pyrimidine Type 1 ATP site inhibitor of TYK2 and JAK1 kinases with IC50 values of 23 nM and 17 nM respectively.