CMD178 is a lead peptide that consistently reduced the expression of Foxp3 and STAT5 induced by IL-2/s IL-2Rα signaling. CMD178 also is an inhibitor of STAT5 and inhibit Treg cell development.

Danvatirsen is an antisense oligonucleotide targeting STAT3 with potential antitumor activity. Danvatirsen binds to STAT3 mRNA, thereby inhibiting translation of the transcript. Suppression of STAT3 expression induces tumor cell apoptosis and decreases tumor cell growth.

5,15-Diphenylporphyrin (5,15-DPP) is a selective STAT3-SH2 antagonist (IC50s of 0.28 µM and 10 µM for STAT3 and STAT1, respectively).

STAT3-IN-7, an aryl sulfonamido azetidine compound, is an orally active STAT3 inhibitor. STAT3-IN-7 has anticancer activities (WO2021016333A1, H182).

2-NP is a selective enhancer of STAT1 transcription. 2-NP can enhance the ability of IFN-γ to inhibit the proliferation of human breast cancer and fibrosarcoma cells.

Napabucasin (BBI-608) is a potent small-molecule inhibitor of STAT3 that has a broad spectrum of activity against stemness-high cancer cells (IC50=0.5-1.5 uM).

A novel small molecule SH2 domain-targeting STAT3 inhibitor with IC50/Kd of 7.3/5 nM; does not bind to the S636A, V637A, and E638A SH2D mutants; effectively inhibits STAT3 phosphorylation (pTyr705 and pSer727) and cancer cell proliferation, impairs mitochondrial function; shows potent activity tumor xenografts in mice; orally bioactive.

A novel STAT3 inhibitor (IC50=18.7 nM; Kd=10 nM) that strongly inhibits STAT3 and STAT5 phosphorylation without upstream kinase inhibition; induces significant growth inhibition in various hematopoietic malignant cells, particularly effective against multiple myeloma, Burkitt lymphoma and leukemia harboring BCR-ABL, FLT3/ITD and JAK2 V617F, oncokinases with their oncogenicities dependent on STAT3/5.

SI-109 (SI 109) is a selective, high-affinity and cell-permeable STAT3 SH2 domain inhibitor with Ki of 9 nM, component of STAT3 degrader SD-36 (PROTAC).

SS-4 (STAT3 inhibitor SS-4) is a highly selective small molecule inhibitor of STAT3 tyrosine phosphorylation that potently inhibits GBM tumorigenesis in vitro and in vivo.SS-4 strongly and selectively inhibits STAT3 Y-705 phosphorylation in MT330 and LN229 GBM cells and inhibits their proliferation and inducs apoptosis with an IC50 of 100 nM.SS-4 increases the expression of STAT3 repressed genes, while decreasing the expression of STAT3 promoted genes.SS-4 markedly reduces the growth of GBM intracranial tumor xenografts.

Stafia-1 prodrug is the cell‐permeable prodrug of Stafia-1, suitable for cell based assays, inhibits tyrosine phosphorylation of STAT5a with selectivity over STAT5b in cultured human leukemia cells.

Stat3 inhibitor H182 is a potent, selective STAT3 inhibitor, inhibits Stat3 DNA-binding activity with IC50 of 0.66 uM.Stat3 inhibitor H182 shows selective inhibition of Stat3:Stat3 DNA-binding activity, over the inhibition of Stat1:Stat3 (IC50 of 3.4-8.3 μM), with far lower potencies against Stat1:Stat1 (IC50 > 15.8 uM) and Stat5:Stat5 activities (IC50 >19.1 uM).Stat3 inhibitor H182 irreversibly and covalently binds (KD=1.97 uM, ITC) to Stat3 key residues Cys426 and Cys468.Stat3 inhibitor H182 inhibits constitutive and ligand-induced Stat3 activation (pY705Stat3) and blocks Stat3 nuclear accumulation with no change in Stat3 protein levels in breast cancer cells, with little or no effects on pS727Stat3, Stat1, JAK2, EGFR, Shc, Erk1/2, Src, or Akt induction.Stat3 inhibitor H182 inhibited anchorage-dependent and independent growth (MDA-MB-231, IC50=1 uM), induced apoptosis, and suppressed Stat3 target gene expression in TNBC cells harboring constitutively-active Stat3.Stat3 inhibitor H182 inhibited growth of breast tumors in mice, enhanced response to radiation and prolonged survival.

STAT3 inhibitor N4 is a small molecule capable of inhibiting the STAT3 SH2 domain with IC50 of 0.57 uM, SPR KD of 1.04 uM, inhibits STAT3 dimerization and transcription in vitro and suppresses pancreatic cancer in vivo.N4 suppresses STAT3 activation in pancreatic cancer cells, suppresses pancreatic cancer cell growth, migration, and induces apoptosis.N4 (20 mg/kg, i.p.) suppresses pancreatic cancer growth, exhibits potent anti-metastatic activity in a pancreatic cancer liver metastasis mouse model, and prolongs survival of tumor-bearing mice.

Prohibitin ligand 1 (Compound 22i), a cardioprotectant prohibitin ligand, induces a phosphorylation of the pro-survival factor STAT3. Prohibitin ligand 1 exhibits in vitro cardioprotectant activities at nanomolar concentrations.

MNK8 is a potent STAT3 (signal transducer and activator of transcription 3) inhibitor. MNK8 inhibits STAT3 activation and reduced its DNA binding ability. MNK8 shows good growth inhibition against hepatocellular carcinoma (HCC) cells. MNK8 induces apoptosis in HCC cells. MNK8 reduces prosurvival proteins expression and migration/invasion of HCC cells.

IST5-002, a potent Stat5a/b inhibitor, selectively inhibits transcriptional activity of Stat5a/b (IC50s: 1.5 μM for Stat5a, 3.5 μM for Stat5b). IST5-002 inducs cell apoptotic and death of prostate cancer cells and chronic myeloid leukemia (CML) cells. IST5-002 can be used in the research of prostate cancer and chronic myeloid leukemia (CML).

(S)-PM-43I is a potent STAT6 inhibitor and can reduce STAT6 phosphorylation level. (S)-PM-43I can be used in allergic lung disease, allergic rhinitis, chronic pulmonary obstructive disease and cancer research[1].

PM-81I is a potent STAT6 inhibitor (targeting the SH2 structural domain) that effectively reduces STAT6 phosphorylation levels. PM-81I can be used in studies of allergic lung disease, allergic rhinitis, chronic obstructive pulmonary disease or cancer[1].

HP590 is an orally active, novel and potent STAT3 inhibitor (STAT3 luciferase activity: IC50=27.8 nM; ATP inhibition: IC50=24.7 nM). HP590 shows anti-proliferative activity to gastric cancer cells and induces apoptosis.

STX-0119 is a selective, orally active STAT3 dimerization inhibitor. STX-0119 inhibits STAT3 transcription with an IC50 of 74 μM.

GYY4137 is a novel, water-soluble hydrogen sulfide (H2S)–releasing molecule with vasodilator and antihypertensive activity. GYY4137 shows potent anti-hepatocellular carcinoma activity through blocking the STAT3 pathway. GYY4137 also shows anti-inflammatory activity.

inS3-54A18 is a potent inhibitor of STAT3 with anti-cancer properties.