Therapeutic modulators of STAT signalling for human diseases

Abstract

The signal transducer and activator of transcription (STAT) proteins have important roles in biological processes. The abnormal activation of STAT signalling pathways is also implicated in many human diseases, including cancer, autoimmune diseases, rheumatoid arthritis, asthma and diabetes. Over a decade has passed since the first inhibitor of a STAT protein was reported and efforts to discover modulators of STAT signalling as therapeutics continue. This Review discusses the outcomes of the ongoing drug discovery research endeavours against STAT proteins, provides perspectives on new directions for accelerating the discovery of drug candidates, and highlights the noteworthy candidate therapeutics that have progressed to clinical trials.

A chemogenomic screening identifies CK2 as a target for pro-senescence therapy in PTEN-deficient tumours

“…2d). In response to cytokines and growth factors, STAT proteins are phosphorylated by receptor-associated kinases and then form homo-or heterodimers that translocate to the nucleus, where they act as transcriptional activators 31 .…”

STAT3 Serine 727 Phosphorylation: A Relevant Target to Radiosensitize Human Glioblastoma

“…To our knowledge, to date, there is no reported specific inhibitor of pSTAT3-S727 capable of discriminating pSTAT3-Y705 and pSTAT3-S727 (40,53). Because pSTAT3-S727 regulation involved several pathways depending on cell types, broad-spectrum kinase inhibitors are useful in exploring STAT3 pathway activation.…”

STAT-Dependent Upregulation of 12/15-Lipoxygenase Contributes to Neuronal Injury after Stroke

“…Unfortunately, very few STAT-specific inhibitors are available at present. 40 (4) As always when considering acute stroke therapy, timing is a major issue. Our findings concerning early activation of STAT6 and STAT1, which confirm earlier reports, suggest that the time window after onset of stroke may be fairly limited.…”