JAK/STAT Inhibitors
JAK/STAT Inhibitors
Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) are two major components in the signaling cascade that transmit extracellular signals across the cell membrane and into the nucleus, thereby altering gene transcription. The JAK/STAT signaling pathway is involved in cell growth, differentiation, survival, and pathogen resistance. Its components are expressed in various cell types but are particularly prominent in immune cells. This pathway mediates the effects of interferons, cytokines, and growth factors. Dysregulation of the JAK/STAT signaling pathway is closely associated with the development of multiple diseases. STATs are transcription factors that bind to the promoter regions of DNA, inducing the expression of downstream DNA sequences. In certain cancers, STAT3 and STAT5 are persistently activated, leading to hyperactive signaling and uncontrolled gene transcription. JAK kinases are activated through transmembrane receptors and are responsible for phosphorylating STATs. Acquired mutations in JAK function are associated with hematologic malignancies such as thrombocytosis, myelofibrosis, and leukemia.
Figure 1: Chemical structure of CYT-387
Aladdin Inhibitors of JAK signaling:
AZD-1480 A126326 | |
Tyrphostin AG490 A126525 | |
Aladdin Inhibitors of STAT signaling:
References:
1. Yu H, Pardoll D, Jove R. Nat Rev Cancer. 2009 Nov;9(11):798-809.
2.Berger A, Sexl V, Valent P, et al. Oncotarget. 2014 Oct 30;5(20):9564-76.
3. Vainchenker W, Constantinescu SN. Oncogene. 2013 May 23;32(21):2601-13.
Aladdin: https://www.aladdinsci.com/