Janus kinase (JAK) is a family of intracellular, nonreceptor tyrosine kinases. The JAK family is composed of four cytoplasmic tyrosine phosphotransferases (kinases), namely JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2). Several cytokines involved in inflammatory pathologies signal via the JAK-STST pathway. Thus, the specific activation of JAKs and STATs determines the biological effects of each cytokine. JAK1 is involved in the signaling of ‘γc’ receptor cytokines (IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21), pro-inflammatory cytokines including IL-6, as well as IFN.

JAK1 is a human tyrosine kinase protein. Importantly, JAK1 plays a critical role in initiating responses to multiple major cytokine receptor families. It interacts with the common gamma chain (γc) of type I cytokine receptors, to elicit signals from the IL-2 receptor family, the IL-4 receptor family, the gp130 receptor family. Meanwhile, it is also important for transducing a signal by type I and type II interferons, and members of the IL-10 family via type II cytokine receptors. Therefore, JAK inhibition has led to a better understanding of the biology of synovial inflammation and bone homeostasis.

TUL01101 is a novel potent, selective and orally active JAK1 inhibitor for the research of rheumatoid arthritis.

TUL01101 exhibits more than 12-fold selectivity for JAK2, JAK3, and TYK2. In human whole blood assay, TUL01101can inhibit cytokine-induced pSTAT. At the same time, TUL01101 also demonstrates excellent metabolic stability in three species (mouse, rat, and dog). Moreover, it is effective activity in the treatment of RA both in collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA) models, with low dose and low toxicity. Thus, TUL01101 has the potential for the research of rheumatoid arthritis.

All in all, TUL01101, a novel potent, selective, and orally active JAK1 inhibitor, has the potential for the research of rheumatoid arthritis.


[1].Spinelli FR, et, al. Rheumatology (Oxford). 2021 May 5;60(Suppl 2):ii3-ii10.

[2]. Zhou S, et, al. J Med Chem. 2022 Dec 22;65(24):16716-16740.