Table 1.
Preclinical STAT inhibitors in breast cancer.
| STAT | Drug/Therapeutic Inhibitor | Main Function | Cancer and/or Cell Type | Ref. |
|---|---|---|---|---|
|
| ||||
| STAT1 | EGCG | Suppresses cell proliferation of breast cancer cells | Breast cancer (MCF-7) cells | [131] |
| STAT1 | Fludarabine | Suppresses STAT1, pSTAT1, and PD-L1 expression in breast cancer cells | Breast cancer (MCF-7, MDA-MB-231 and MDA-MB-468) cells | [139] |
| STAT1 | Fludarabine and doxorubicin | Decreased STAT1-positive cells and suppressed mammary tumor growth of murine mammary tumor cells | Breast cancer (MDA-MB-231 and PNA.Met1) cells; PNA.Met1 (murine mammary tumor line derived from spontaneous mammary tumors from MMTV-PyMT model) | [120] |
| STAT3 | 10,11-dehydrocurvularin (DCV) | Macrolide, derived from marine fungus, inhibits pSTAT3 without impacting upstream JAK1 or JAK2, leading to decreased breast cancer cell proliferation, migration, and invasion; DCV suppressed tumor growth through inhibited pSTAT3 | Breast cancer (MDA-MB-231 and MDA-MB-468) and mammary epithelial (MCF-10A) cells; MDA-MB-231 cells in mouse xenografts | [366] |
| STAT3 | 17o | Decreases pSTAT3 in breast cancer cells | Breast cancer (MDA-MB-468) and multiple myeloma cells | [367] |
| STAT3 | 6Br-6a | Induces cell cycle arrest and apoptosis by blocking activation of STAT3; decreases tumor growth and size in mouse xenografts | Breast cancer (MDA-MB-231 and MCF-7) cells; MDA-MB-231 in right flank of nude mice | [368] |
| STAT3 | 7β-(3-Ethyl-cis-crotonoyloxy)– 1α-(2-methylbutyryloxy)– 3,14-dehydro-Z-notonipetranone (ECN) | A sesquiterpenoid (from Farfarae Flos, traditional medicine used to treat inflammation) suppresses pSTAT3, pJAK1/2, pSrc and induces apoptosis in breast cancer cells | Breast cancer (MDA-MB-231) cells | [369] |
| STAT3 | Alantolactone | A sesquiterpene lactone induces apoptosis and ROS levels; activates caspases and decreases mitochondrial membrane potential and pSTAT3 in breast cancer cells | Breast cancer (MDA-MB-231 and MCF-7) cells | [370] |
| STAT3 | Bazedoxifene | Suppresses pSTAT3, cell proliferation, migration and invasion of breast cancer cells; induces apoptosis in breast cancer cells | Breast cancer (SUM159, MDA-MB-231, and MDA-MB-468) cells | [371] |
| STAT3 | Betulinic acid | Inhibits proliferation, migration, and invasion of breast cancer cells; decreases tumor growth, volume, and lung metastasis in vivo | Breast cancer (MCF-7, 4T1, and MDA-MB-231) cells; subcutaneous 4T1 cells in BALB/C mice | [372] |
| STAT3 | Bisindole-PBD (5b) | Suppresses angiogenesis by suppressing expression of VEGF and STAT3 in breast cancer cells | Breast cancer (MDA-MB-231 and MCF-7) and human endothelial cells | [373] |
| STAT3 | BP-1–102 | Analog of S31–201.1066; blocks pSTAT3 and STAT3 activation, suppresses growth, migration, and invasion of tumor cells and suppresses expression of STAT3-target genes; inhibits growth of human breast tumor xenografts in mice | Breast cancer (MDA-MB-231), prostate, non-small cell lung cancer, and pancreatic cancer cells; MDA-MB-231 xenografts in mice | [374] |
| STAT3 | Cantharidin | Decreases cell growth in breast cancer cells, inhibited adhesion of breast cancer cells to platelets | Breast cancer (MCF-7) cells | [375] |
| STAT3 | Cantharidin | Inhibits cell proliferation, migration, and invasion and induces cell cycle arrest in TNBC cells; inhibits tumor growth in xenograft mouse model | Breast cancer (MDA-MB-231) cells; MDA-MB-231 cells in breast xenograft mouse model | [376] |
| STAT3 | Cantharidin | Inhibits cell proliferation and autophagy and induced apoptosis of TNBC cells; inhibited growth of TNBC xenografts in nude mice | Breast cancer (MDA-MB-231 and MDA-MB-468) cells; MDA-MB-231 and MDA-MB-468 cells in nude mice | [377] |
| STAT3 | Caffeic acid p-nitro-phenethyl ester (CAPE-pNO2) | CAPE-pNO2 decreases pEGFR, pSTAT3, pAkt, MMP2, MMP9, and VEGFA; suppresses breast cancer cell proliferation, migration, and invasion; suppresses tumor growth and induces apoptosis in xenograft mouse model | Breast cancer (MDA-MB-231) cells; subcutaneous injection of MDA-MB-231 cells in nude mice | [378] |
| STAT3 | Carfilzomib | Decreases proliferation and mitosis in breast cancer cell lines; decreases serum IL-6 in mice with MDA-MB-231 tumor | Breast cancer (MDA-MB-231 and MDA-MB-468) cells; MDA-MB-231 cells in nude mice | [379] |
| STAT3 | Catechol | Inhibits proliferation and mammosphere formation (and CD44high/CD24low subpopulation) of breast cancer cells | Breast cancer (MDA-MB-231 and MCF-7) cells | [380] |
| STAT3 | CDDO-Methyl Ester (CDDO-ME) | Inhibits IL-6-induced and constitutive JAK1 activity, and inhibits IL-6-induced STAT3 activation and dimerization | Breast cancer (MDA-MB-468) and cervical cancer cells | [381] |
| STAT3 | Compound 6b | Curcumin-benzo[b]thiophene 1, 1-dioxide (Curcumin-BTP) hybrids as STAT3 inhibitors; Compound 6B suppressed pSTAT3, nuclear translocation, and DNA-binding activity in breast cancer cells; Compound 6B induces apoptosis in breast cancer cells, but not normal breast epithelial cells; inhibits IL-6-mediated pSTAT3; suppresses tumor growth of breast cancer cells in mice with reduced pSTAT3 in tumors | Breast cancer (MCF-7), normal breast epithelial (MCF-10A), and normal liver cells; MCF-7 cells subcutaneously injected in BALB/C mice | [382] |
| STAT3 | Coumarin-benzo[b]thiophene 1, 1-dioxide | Decreases pSTAT3 and cell proliferation and induced apoptosis and ROS generation of breast cancer cells; decreased tumor growth and pSTAT3 in vivo | Breast cancer (MDA-MB-231, MCF-7, and 4T1), mammary epithelial (MCF-10A), hepatocellular carcinoma, and colonic carcinoma cells; 4T1 mouse xenograft model | [383] |
| STAT3 | CPA-1, CPA-7 | Inhibition of constitutive STAT3 activation and decrease in pSTAT3 and cell viability and induces apoptosis in breast cancer cells | Breast cancer (MDA-MB-231, MDA-MB-435, MDA-MB-453, MCF-7, and MDA-MB-468), melanoma, prostate cancer, lung carcinoma and colon cancer cells | [384] |
| STAT3 | Cucurbitacin E | (CuE) inhibits growth and pSTAT3 and induces apoptosis and cell cycle arrest of breast cancer cells | Breast cancer (MDA-MB-231 and Bcap-37) cells | [385] |
| STAT3 | Curcumin alone and curcumin with EGCG | Curcumin and epigallocatechin gallate (EGCG) reduced pSTAT3, STAT3 interaction with NFkB, CD44-positive cells, and mammospheres | Breast cancer (MDA-MB-231 and MCF-7) cells | [267, 386] |
| STAT3 | Cyanidin-3-glucoside (C3G) | C3G, an anthocyanin in many fruits, reduced angiogenesis by inhibiting VEGF expression and secretion in breast cancer cells | Breast cancer (MDA-MB-231 and Hs-578 T) cells | [387] |
| STAT3 | Deguelin | Decreases pSTAT3 and expression of EGFR-downstream target proteins and cell proliferation of breast cancer cells; inhibits growth of MDA-MB-231 cells in dorsal flank of nude mice | Breast cancer (MDA-MB-231, MDA-MB-468, BT-20 and BT-549) cells; MDA-MB-231 cells in dorsal flank of nude mice | [388] |
| STAT3 | Dihydrotanshinone (DHTS) | Decreases mammosphere formation of breast cancer cells; inhibits tumor growth in mouse xenograft model | Breast cancer (MDA-MB-231 and MCF-7) cells; MCF-7 in tumor xenografts in mice | [389] |
| STAT3 | DT-13 | Inhibits migration via suppression of pSTAT3 and PLOD2 expression in breast cancer cells; DT-13 had little effect on tumor growth, but decreased lung and liver metastasis burden in mice | Breast cancer (MDA-MB-231 and MD-MB-468) and pre-adipocyte cells; MDA-MB-231 in orthotopic xenograft tumor model | [390] |
| STAT3 | Esculentoside A | Derived from root of Phytolacca esculenta; inhibits proliferation and mammospheres and induces apoptosis in breast cancer cells; suppresses breast CSC initiated tumor growth in mice | Breast cancer (EMT6, MCF-7), normal mammary epithelial (MCF10A), and normal liver cells | [271] |
| STAT3 | Eupalinolide J | Suppresses pSTAT3, proliferation and induces apoptosis and cell cycle arrest of TNBC cells; suppresses tumor growth in vivo | Breast cancer (MDA-MB-231 and MDA-MB-468) and mammary epithelial (MCF-10A) cells; MDA-MB-231 cells in nude mouse xenograft model | [391] |
| STAT3 | Evista (Raloxifene-HCl) | (Raloxifene-HCl) Inhibits pSTAT3 and IL-6-induced pSTAT3, decreases cell viability, and increases caspase-3 activity in breast cancer cells | Breast cancer (MCF-7, MDA-MB-231, and SUM159), colon cancer, multiple myeloma, and Hela cells | [392] |
| STAT3 | FLLL31/FLLL32 | Derived from curcumin (main compound in turmeric); designed to bind JAK2 and STAT3 SH2 domain; downregulates pSTAT3, DNA-binding activity, cell viability, and invasion of breast cancer cells; induces apoptosis of breast cancer cells; FLLL32 suppresses tumor growth and vascularization in mouse xenografts | Breast cancer (MDA-MB-231, SK-BR-3, MDA-MB-468, MDA-MB-453, and SUM159), pancreatic cancer, and human embryonic kidney cells; MDA-MB-231 mouse xenografts | [268] |
| STAT3 | Flubendazole | Inhibits pSTAT3 and cell viability and induces apoptosis in TNBC cells; suppresses BCSC-enriched TNBC tumor growth, angiogenesis, and metastasis in vivo | Breast cancer (MDA-MB-231, Hs578T, BT-549, and 4T1) cells; 4T1 cells in MFP of BALB/C mice | [393] |
| STAT3 | Galiellalactone, SG-1709, and SG-1721 | Galiellalactone and two analogues (SG-1709 and SG-1721) block pSTAT3 and suppress cell viability and proliferation in TNBC cells; SG-1721 induces cell cycle arrest and apoptosis; SG-1721 inhibits tumor growth of TNBC cells in vivo | Breast cancer (BT-549, BT-20, MDA-MB-468, MCF-7, T47D, SK-BR-3, MDA-MB-453) and mammary epithelial (MCF-10A) cells; TNBC cells (exact cell line not stated) subcutaneous implantation in nude mice | [394] |
| STAT3 | Ganoderic acid A | Decreases pJAK2, pSTAT3 and suppresses invasion and induces apoptosis of breast cancer cells | Breast cancer (MDA-MB-231) cells | [395] |
| STAT3 | Genistein | Phytotherapeutic Genistein suppresses breast cancer cell proliferation | Breast cancer (MDA-MB-453) cells | [396] |
| STAT3 | GO-Y030 | Suppresses pSTAT3, STAT3 transcriptional activity, cell viability and induces apoptosis in breast cancer cells | Breast cancer (MDA-MB-231) and pancreatic cancer cells | [397] |
| STAT3 | HJC0123 | Inhibits pSTAT3 and STAT3-mediated luciferase reporter activity and induced apoptosis in TNBC cells; inhibits tumor growth in TNBC xenograft mouse model | Breast cancer (MCF-7 and MDA-MB-231) and pancreatic cancer cells; MDA-MB-231 cells in xenograft mouse model | [398] |
| STAT3 | HJC0416 | (5-chloro-N-(1,1-dioxo-1 H-1λ6-benzo[b]thiophen-6-yl)–2-hydroxybenzamide) HJC0416 inhibits cell cycle progression and promotes apoptosis in breast cancer cells; HJC0416 reduces tumor volume in breast cancer murine xenografts in vivo | Breast cancer (MDA-MB-231) cells; MDA-MB-231 tumor xenografts in mice | [399] |
| STAT3 | Hydrazinocurcumin | (Analog of curcumin) inhibits pSTAT3, downstream STAT3 target genes, cell migration and invasion and induces apoptosis in breast cancer cells | Breast cancer (MDA-MB-231 and MCF-7) cells | [400] |
| STAT3 | Ilamycin C | Ilamycins are cyclic peptides produced by (isolated from) Streptomyces; Increased toxicity against TNBC cells vs. LumA cells; suppresses pSTAT3, proliferation, migration and invasion and induces apoptosis in TNBC cells | Breast cancer (MDA-MB-231, BT-549, and MCF-7) and normal breast (MCF10A) cells | [180] |
| STAT3 | IS3 295 | Decreased cell proliferation and constitutive STAT3 activation in breast cancer cells; induced apoptosis and promoted cell cycle arrest in breast cancer cells | Breast cancer (MDA-MB-231, MDA-MB-435, MDA-MB-453, and MDA-MB-468), prostate cancer, melanoma, pancreatice cancer, and fibroblast cells | [401] |
| STAT3 | Isoharringtonine (IHT) | IHT decreases pSTAT3 and suppresses proliferation, migration, and BCSCs in breast cancer cells | Breast cancer (HCC1937, HCC1806 and MCF-7) cells | [402] |
| STAT3 | LLL12 | Inhibits STAT3 phosphorylation, DNA binding activity, STAT3-dependent luciferase activity, cell viability and migration in breast cancer cells; decreased tumor volume in mouse tumor xenografts | Breast cancer (MDA-MB-231, MDA-MB-453, and SK-BR-3), pancreatic cancer, glioblastoma, human hepatocytes, and human lung fibroblast cells; MDA-MB-231 tumors in mice | [403] |
| STAT3 | LLY17 | Inhibits pSTAT3 in breast cancer cells; suppresses cell viability and migration and induces apoptosis in TNBC cells, not Luminal A breast cancer cells; suppresses tumor growth of 4T1 cells in vivo | Breast cancer (MDA-MB-468, MDA-MB-231, SUM159, BT-549, and 4T1) cells; 4T1 in MFP mouse model in BALB/C mice | [404] |
| STAT3 | LYR71 | 6-methyl-2-propylimino-6, 7-dihydro-5 H-benzo [1,3]-oxathiol4-one (LYR71), a derivative of trimeric resveratrol, suppresses pSTAT3, MMP9 expression and activity, migration and invasion of breast cancer cells; inhibits growth of MDA-MB-231 tumors in mice | Breast cancer (MDA-MB-231) cells; MDA-MB-231 subcutaneously injected in flank of nude mice | [405] |
| STAT3 | Napabucasin | (BBI608) Decreases pSTAT3, cell viability, and sternness of breast cancer cells | Breast cancer (MCF-7) cells | [406] |
| STAT3 | Naringenin | Decreases pSTAT3, cell viability and induces apoptosis of breast cancer cells; increases caspase 3 and 9 activity | Breast cancer (MDA-MB-231) cells | [407] |
| STAT3 | Niclosamide | Inhibits proliferation, migration, and invasion and induces apoptosis in breast cancer cells; decreased IL-6 and pSTAT3 in breast cancer cells | Breast cancer (MDA-MB-468 and MCF-7) cells | [408] |
| STAT3 | Nifuroxazide | Reduces pSTAT3 and expression of MMP2 and MMP9, decreases cell viability, migration and invasion and induces apoptosis of breast cancer cells; suppressed tumor growth of 4T1 cells in vivo | Breast cancer (MDA-MB-231, MCF-7, and 4T1) cells; 4T1 cells in BALB/C mice | [409] |
| STAT3 | Pectolinarigenin | Suppresses proliferation, migration and invasion and induces apoptosis of breast cancer cells; had no effect on tumor growth of subcutaneously injected 4T1 cells, but decreased spontaneous lung metastases; increased CD8 + T cells in peripheral blood and in lung metastatic tissue | Breast cancer (4T1, MDA-MB-231, and MCF-7) cells; subcutaneous 4T1 cells in mice | [410] |
| STAT3 | Picrasidine G | Decreases pSTAT3 and STAT3-regulated gene expression and induced apoptosis in TNBC cells | Breast cancer (MCF-7, T47D, MDA-MB-361, SKBR3, Hs578T, MDA-MB-231 and MDA-MB-468) and mammary epithelial (MCF10A) cells | [411] |
| STAT3 | Pimozide | Decreases pSTAT3, suppresses migration and invasion and increases apoptosis in TNBC cells | Breast cancer (BT-549, MDA-MB-231, MDA-MB-468, and HCC1806) cells | [260] |
| STAT3 | Piperlongumine (PL) | PL, a natural alkaloid, decreases pSTAT3 and pJAK2, suppresses breast cancer cell proliferation, colony formation, and induces apoptosis | Breast cancer (MDA-MB-231 and MDA-MB-453) cells | [412] |
| STAT3 | PM-73 G | Phosphopeptidomimetic prodrug blocks constitutive pSTAT3, but not Akt or Tyr861 phosphorylation in MDA-MB-468 cells (first ref). Treatment inhibits orthotopic MDA-MB-468 human breast tumor xenograft tumor proliferation in nude mice (second ref) | Breast cancer (MDA-MB-468) cells; MDA-MB-468 human breast tumor xenografts in nude mice | [413, 414] |
| STAT3 | Pyrimethamine | Decreases pSTAT3 in breast cancer cells and mouse tumors; decreases proliferation and invasion of breast cancer cells and decreases T reg cells in mice | Breast cancer (TUBO) cells | [415] |
| STAT3 | Resveratrol (RES) | (aka RES, aka trans-3,4′,5-trihydroxystilbene) Blocks Src tyorisine kinase activity, thereby inhibiting constitutive STAT3 activation (pSTAT3), cell proliferation, cell cycle progression and induces apoptosis in breast cancer cells | Breast cancer (MDA-MB-231 and MDA-MB-468), pancreatic cancer, prostate cancer, and mouse fibroblast cells | [416, 417] |
| STAT3 | rPP-C8 | Recombinant STAT3-specific inhibitor (rPP-C8) suppresses STAT3 target gene expression and proliferation, and induced apoptosis of breast cancer cells | Breast cancer (SKBR3, MDA-MB-468, MCF-7, T47D, and 4T1), glioblastoma, melanoma, and prostate cancer cells | [418] |
| STAT3 | S3I-1757 | Disrupts STAT3-STAT3 dimerization, which is required for nuclear translocation; inhibits pSTAT3, nuclear accumulation of P-Y705-STAT3, STAT3 DNA-binding and suppresses expression of STAT3 target genes (BCL2Ll, BIRC5, CCND1, and MMP9); suppresses migration and invasion of breast cancer cells | Breast cancer (MDA-MB-468, MDA-MB-231, and MDA-MB-453), lung cancer, mammary epithelial (MCF10A), and embryonic kidney cells | [419] |
| STAT3 | S3I-201 | (NSC #74859) Chemical probe inhibitor of STAT3 activity; binds to STAT3 phosphotyrosine peptide derived from the x-ray crystal structure of the STAT3beta homodimer; inhibits growth and induces apoptosis preferentially in tumor cells; inhibits expression of stat3-regulated genes (cyclin D1, Bcl-xl, and survivin) and inhibits growth of human breast tumors in vivo | Breast cancer (MDA-MB-231, MDA-MB-435, and MDA-MB-468) and other (NIH 3T3/v-Src) cells; MDA-MB-231 breast tumor xenografts in mice | [256] |
| STAT3 | Sabutoclax | Pan-active BCL-2 protein antagonist; induces apoptosis and caspase activity, and decreases pSTAT3 and CD44high/CD24low subpopulation in breast cancer cells; increased apoptosis, decreases CD44 and ALDH1 cells and decreases pSTAT3 in fresh human breast tumors | Breast cancer (MCF-7 and Cal51) cells; human breast tumor samples | [420] |
| STAT3 | Saikosaponin b2 (SSb2) | Saikosaponin b2 (SSb2) decreases pSTAT3, VASP, MMP2, and MMP9; suppresses breast cancer cell proliferation and migration; limited to no liver and kidney toxicity in mice | Breast cancer (MCF-7) cells | [270] |
| STAT3 | Satraplatin | A tetravalent platinum derivative decreases pSTAT3 and increases apoptosis of breast cancer cells | Breast cancer (MCF-7 and MDA-MB-231) cells | [249] |
| STAT3 | Schisandrin A | Inhibits P-gp mRNA and protein expression in breast cancer cells; decreased pSTAT3 in breast cancer cells | Breast cancer (MCF-7) and DOX-resistant (BEL-7402 and K-562) cells | [421] |
| STAT3 | SH48 | SH48 inhibits STAT3 dimerization and translocation into the nucleus; induces autophagy of mammary epithelial cells transformed by H-ras oncogene | Mammary epithelial cells transformed by H-ras oncogene (MCF10A-ras), prostate cancer, and cervical cancer cells | [422] |
| STAT3 | SH5–07, SH4–54 | Hydroxamic acid (SH5–07) and benzoic acid (SH4–54) analogues inhibit STAT3 activation and DNA binding activity; suppressed breast cancer cell proliferation to greater extent when the cells exhibit constitutive STAT3 activity; both compounds (individually) suppressed growth of breast cancer cells and decreased expression of STAT3-target genes in vivo | Breast cancer (MDA-MB-231 and MCF7), pancreatic, prostate, and normal mouse fibroblast cells; MDA-MB-231 cells injected into left flank athymic mice | [259] |
| STAT3 | PMMB-187 | PMMB-187 (a shikonin derivative) inhibits constitutive STAT3 activation, nuclear translocation, DNA binding activity, and subsequent target gene expression in breast cancer cells; induces breast cancer cell apoptosis; inhibits breast tumor growth in mouse xenografts | Breast cancer (MCF-7, MDA-MB-231 and MDA-MB-468) and non-tumor breast epithelial (MCF-10A) cells; MDA-MB-231 cells in mouse xenografts | [423] |
| STAT3 | Silibinin | (Legasil), Made from flavonoid extracts from milk thistle seeds; blocks STAT3 signaling in reactive astrocytes resulting in decreased brain metastases from multiple cancers (including breast cancer) in mice | Brain-tropic breast cancer (MDA-MB-231-BrM2) and melanoma cells | [263] |
| STAT3 | SPI | Potent and selective inhibitor of the STAT3 SH2 domain; blocks constitutive pSTAT3, DNA binding and activity, and transcriptional function in multiple cancers | Breast cancer (MDA-MB-231, MDA-MB-435, MCF-7), pancreatic cancer, prostate cancer, non-small cell lung cancer, and normal mouse fibroblast cells | [424] |
| STAT3 | STA-21 | (NSC #628869) STA-21 inhibits STAT3 DNA binding activity, dimerization, and STAT3-dependent luciferase activity; inhibits survival of breast cancer cells with constitutive STAT3 signaling | Breast cancer (MDA-MB-231, MDA-MB-435S, MDA-MB-453, MDA-MB-468, and MCF-7), human ovarian carcinoma, and human skin fibroblast cells | [425] |
| STAT3 | Stattic | (6-nitro-benzo[b]thiophene-1,1-dioxide 1) Retains STAT3 in cytosol by inhibiting binding of a phosphotyrosine-containing peptide derived from the gp130 receptor to the STAT3 SH2 domain | Breast cancer (MDA-MB-231 and MDA-MB-435S) and HepG2 cells | [258] |
| STAT3 | STX-0119 | Inhibited STAT3 promoter binding and pSTAT3 in breast cancer cells | Breast cancer (MDA-MB-468) cells | [426] |
| STAT3 | WP1066 | (modified structure of AG490) WP1066 decreases pSTAT3 in breast cancer cells; decreases breast cancer brain metastases in intracardiac mouse model; reduces proliferation, MM9 expression, and VEGF expression in brain metastatic cells | Breast cancer (MDA-MB-231BR and BT-474BR) cells; MDA-MB-231BR brain metastases in mice | [261, 262] |
| STAT3 | XZH-5 | Decreases pSTAT3, STAT3 downstream target genes, colony formation and migration and induces apoptosis in breast cancer cells, inhibits IL-6-induced pSTAT3 and nuclear accumulation in breast cancer cells | Breast cancer (MDA-MB-231, SUM159 and MCF-7) and pancreatic cancer cells | [427] |
| STAT3 and STAT5 | SH-4–54 | Suppressed breast cancer cell proliferation; decreases TNBC cell plasma membrane antiporter system (xC) and cystine import, both of which are essential for cancer cells to adapt to increased levels of ROS | Breast cancer (MDA-MB-231 and T47D) cells | [428] |
| STAT3 and STAT5 | Withacnistin | Blocks EGF- or IL-6-stimulated STAT3 and STAT5 binding to EGFR and gp130; suppresses pSTAT3 nuclear nuclear translocation and DNA binding activity resulting in decreased transactivation and STAT3-target gene expression and induces apoptosis in breast cancer cells; treatment suppresses breast tumor growth | Breast cancer (MDA-MB-468), lung cancer, and mouse fibroblast cells | [429] |
| STAT5 | CAS 285986–31-4 | Nonpeptidic nicotinoyl hydrazine compound STAT5 inhibitor; decreases pSTAT5 and proliferation in breast cancer cells | Breast cancer (T47D) cells | [314] |
| STAT5a | Pimozide | Pimozide sensitives DOX-resistant cells through the suppression of STAT5a; decreases tumor growth in subcutaneous xenograft mouse model | Breast cancer (MCF-7) cells | [322, 328] |
| STAT6 | AS1517499 | Inhibits pSTAT6 and M2 macrophage differentiation of mouse macrophages; suppresses tumor growth and liver metastasis of orthotopic 4T1 breast cancer mouse model | Breast cancer (4T1) and mouse macrophage cells; 4T1 cells in orthotopic mouse model | [353] |