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. Author manuscript; available in PMC: 2021 Aug 1.
Published in final edited form as: Cell Signal. 2020 Apr 20;72:109639. doi: 10.1016/j.cellsig.2020.109639

Table 2:

Pharmacological approaches to STAT inhibition

Molecule Effect Target(s) Indication (Clinical Trial Phase) Ref
JAK
Ruxolitinib Direct inhibition of JAKs JAK1, JAK2 Approved for treatment of polycythemiavera and myelofibrosis (MF) (Verstovsek et al., 2010)
Tofacitinib Direct inhibition of JAKs JAK1, JAK3 Treatment of Rheumatoid Arthritis (RA) and ulcerative colitis (Kremer et al., 2009)
Baricitinib Direct inhibition of JAKs JAK1, JAK2 Treatment of RA (Taylor et al., 2017)
VX-509 Direct inhibition of JAK3 JAK3 Treatment of RA (Genovese et al., 2016)
Fedratinib Direct inhibition of JAK2 JAK2 Treatment of MF (Harrison et al., 2017)
Upadacitinib Direct inhibition of JAK1 JAK1 Treatment of RA (Genovese et al., 2018)
STAT3
Triptolide Inhibits phosphorylation of JAK2/ STAT3 JAK/STAT3 pathway Phase 3 trial for HIV, Uncontrolled trial in PKD (Jing et al., 2018)
AZ505 Inhibits STAT3 phosphorylation SMYD2 Not Applicable (Ferguson et al., 2011)
Anti-IL10 Inhibition of macrophages Macrophages Not Applicable (Peda et al., 2016)
Pyrimethamine STAT3 dimerization STAT3 Treatment for Toxoplasmosis, (Takakura et al., 2011)
Curcumin Decreased STAT3 phosphorylation Wnt, TNF-a, MAPK, HIF1, notch-1 and mTOR and STAT3 Phase 3 trial planned for CKD Phase 2 Trial for AKI Phase 4 trial planned for PKD (Leonhard et al., 2011)
Nifuroxazide Reduced renal macrophage infiltration, TNF-a, IL-18, Decreased STAT3 phosphorylation Jak2/ STAT3, Tyk2 Treatment of colitis and diarrhea (Said et al., 2018)
Imatinib Inhibits STAT3 phosphorylation Tyr-Kinases Treatment of Chronic myeologenous leukemia (CML), gastrointestinal stromal tumors (GISTs) (Zaki et al., 2018)
Crizotinib Inhibits STAT3 phosphorylation c-Met Treatment of non-small cell lung cancers,
Phase 2 trials for renal cancers		 (Mesarosova et al., 2017)
Stevia/Stevioside Inhibits STAT3 phosphorylation, Inhibits ERK1/2 phosphorylation Not known Several trials for diabetes mellitus (DM) and obesity (Potočnjak et al., 2017)
Cryptotanshinone Inhibits STAT3 phosphorylation SH2 Domain of STAT3 Trial planned for polycystic ovary syndrom (Chen et al., 2017)
Cinnamaldehyde Inhibits STAT3 phosphorylation JAKs Trials planned for DM and obesity (Huang et al., 2015)
Paclitaxel Inhibits nuclear translocation Tubulin Treatment of breast, ovarian and lung cancer (Zhang et al., 2015)
Resveratrol Inhibits pY-STAT3 and acetyl-STAT3 Sirtuin 1 Several trials for CKD and diabetic nephropathy (Ni et al., 2014b)
MS-275 Inhibits STAT3 and Akt phosphorylation HDAC1 Phase 1 trial for CML, acute myeloid leukemia (AML), and breast cancer Phase 2 trial for renal cancer (Tang et al., 2014)
Oligodeoxynucleotidedecoys Decreased STAT3 translation STAT3 mRNA Not Applicable (Miklossy et al., 2013)
Antisense oligonucleotide Decreased STAT3 translation STAT3 mRNA Not Applicable (Miklossy et al., 2013)
STAT5
Pimozide Decreased STAT5 phosphorylation Not known Approved for treatment of Tourette Syndrome (Nelson et al., 2011)
E804 (Indirubin derivatives) Decreased STAT5 phosphorylation and DNA binding activity Most likely Tyr kinases Not Applicable (Nam et al., 2012)
Chromone based nicotinyl hydrazine Weakly inhibit STAT5 phosphorylation STAT5 Not Applicable (Müller et al., 2008)
Stafib-2 STAT5b SH2 domain inhibitor STAT5 Not Applicable (Elumalai et al., 2017)
AC-3-19 STAT5 SH2 domain inhibitor STAT5 Not Applicable (Cumaraswamy et al., 2014)
AC-4-130 STAT5 SH2 domain inhibitor STAT5 Not Applicable (Wingelhofer et al., 2018)
STAT6
Teriflunomide Inhibits Phosphorylation of STAT6 Various Protein Kinases Approved for treatment of Multiple Sclerosis (Bar-Or et al., 2014; Olsan et al., 2011)
AS1517499 Inhibits Phosphorylation of STAT6 STAT6 Not Applicable (Chiba et al., 2009)
Niflumic acid Inhibits Phosphorylation of STAT6 JAK2/ STAT6 Commonly used for treatment of Rheumatoid Arthritis (Nakano et al., 2006)
YM-341619 Inhibits Phosphorylation of STAT6 STAT6 Not Applicable (Ohga et al., 2008)
PM-43I STAT5/STAT5 SH2 Domains STAT5/STAT6 Not Applicable (Knight et al., 2018)
Tralokinumab IL-13 neutralizing monoclonal antibody IL-13 Positive phase 2b study for AD, currently in phase 3 study for AD Wollenberg et al., 2019
Lebrikizumab IL-13 neutralizing monoclonal antibody IL-13 Positive phase 2b results for Atopic Dermatitis (Corren et al., 2011; Hanania et al., 2015; Noonan et al., 2013; Scheerens et al., 2014; Simpson et al., 2018)