IL-6 is a widespread cytokine which participates in many biological responses. All members of the IL-6 cytokine family are able to activate STAT3, and STAT3 is also recognized as the main mediator of IL-6 functions. IL-6 binding to cell surface receptors results in the activation of the Janus kinases(JAKs) which cause STAT3 phosphorylated. Then activated STAT3 dimerizes translocates to the nucleus and combines with target genes with specific sites, then activats DNA transcriptional activity. Studies show that the abnormally activated STAT3 in cells plays an important role in tumorigenesis and malignant transformation. Meanwhile, STAT3 is a valid target for novel anticancer drug design. So far, many methods, such as structure-based virtual screening, high throughput screening, fragment-based drug design, have been used to screen and design novel STAT3 inhibitors, and thus several classes of small molecule compounds have been identified as STAT3 inhibitors. In this review, we mainly focus on the small molecule IL-6/STAT3 inhibitors especially target STAT3 protein which have been optimized and identified since 2013.

Contents
1 Introduction
2 Small molecule inhibitors of IL-6/STAT3 signaling pathway
2.1 1,4-Naphthoquinones
2.2 Quinolines
2.3 Derivatives of benzo[b]thiophene-1,1-dioxide
2.4 Derivatives of Niclosamide
2.5 Derivatives of salicylic acid
2.6 6-Aminobenzo[d]thiazole-2-thiols
2.7 Tetrahydropyridinepyrazoles
2.8 Flavonoids
2.9 Coumarins
2.10 Metal-containing compounds
2.11 Other small molecule IL-6/STAT3 inhibitors
3 Conclusion