IFN-γRβ Inhibitors

The inhibitors listed above are not direct inhibitors of IFN-γRβ but influence the IFN-γ signaling pathway by targeting various components of the cascade. The majority of these compounds are kinase inhibitors, reflecting the central role of kinase activity in cytokine receptor signaling. The Janus kinase (JAK) family is particularly crucial in this regard, as evidenced by the presence of several JAK inhibitors like Ruxolitinib, Tofacitinib, and Baricitinib. These inhibitors prevent the phosphorylation and activation of STAT proteins, key transducers in the IFN-γ signaling pathway, thereby indirectly modulating the activity of IFN-γRβ.

STAT inhibitors such as Stattic and WP1066 specifically target the STAT family of transcription factors, which are activated upon IFN-γRβ engagement and are essential for mediating the cellular responses to IFN-γ. By inhibiting STATs, these compounds disrupt the downstream effects of IFN-γ signaling.Additionally, multi-targeted kinase inhibitors like Dasatinib, Sorafenib, and Imatinib, although not specific to the IFN-γ pathway, can affect it indirectly due to their broad spectrum of action. For instance, Dasatinib's inhibition of SRC family kinases can potentially influence signaling networks that intersect with IFN-γ pathways. Curcumin, a natural compound with a wide range of biological activities, demonstrates the potential for non-specific modulation of signaling pathways, including those associated with IFN-γRβ.