STAT5
STAT5 comprises STAT5A and STAT5B, transcription factors that regulate hematopoietic cell proliferation, differentiation, and apoptosis[1]. Mechanistically, STAT5 tyrosine phosphorylation in peripheral T cells is driven by cytokine receptor signaling rather than the T-cell receptor complex[2]. This cytokine-linked pathway supports immune regulation, lymphocyte development, and cell survival programs[3]. In disease contexts, STAT5B deficiency is associated with growth failure, immunodeficiency, and severe pulmonary disease[4]. Compared with STAT5A, STAT5B shows dominant activity in effector and regulatory T-cell responses, with paralog dose explaining much functional specificity[5]. In BCR/ABL leukemia models, STAT5B, but not STAT5A, serves as the major STAT5 isoform driving leukemogenesis[6]. For experimental applications, AC-4-130 directly binds STAT5 and disrupts activation, dimerization, nuclear translocation, and STAT5-dependent transcription in AML models[7]. Pimozide also decreases survival of chronic myelogenous leukemia cells resistant to kinase inhibitors[8].
References:
- [1]. Nosaka T, et al. STAT5 as a molecular regulator of proliferation, differentiation and apoptosis in hematopoietic cells. EMBO J. 1999 Sep 1;18(17):4754-65. [Content Brief]
- [2]. Moriggl R, et al. Stat5 activation is uniquely associated with cytokine signaling in peripheral T cells. Immunity. 1999 Aug;11(2):225-30. [Content Brief]
- [3]. Smith MR, et al. STAT5b: A master regulator of key biological pathways. Front Immunol. 2023 Jan 23;13:1025373. [Content Brief]
- [4]. Nadeau K, et al. STAT5b deficiency: an unsuspected cause of growth failure, immunodeficiency, and severe pulmonary disease. J Pediatr. 2011 May;158(5):701-8. [Content Brief]
- [5]. Villarino A, et al. Signal transducer and activator of transcription 5 (STAT5) paralog dose governs T cell effector and regulatory functions. Elife. 2016 Mar 21;5:e08384. [Content Brief]
- [6]. Kollmann S, et al. Twins with different personalities: STAT5B-but not STAT5A-has a key role in BCR/ABL-induced leukemia. Leukemia. 2019 Jul;33(7):1583-1597. [Content Brief]
- [7]. Wingelhofer B, et al. Pharmacologic inhibition of STAT5 in acute myeloid leukemia. Leukemia. 2018 May;32(5):1135-1146. [Content Brief]
- [8]. Nelson EA, et al. The STAT5 inhibitor pimozide decreases survival of chronic myelogenous leukemia cells resistant to kinase inhibitors. Blood. 2011 Mar 24;117(12):3421-9. [Content Brief]
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STAT5 Related Products (69)
Related Products (69)
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Antibodies (5)
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Ritlecitinib
0 ImagesSynonyms: PF-06651600Ritlecitinib (PF-06651600) is a highly selective, orally active, irreversible covalent JAK3 inhibitor (IC50=33 nM) without inhibitory activity towards JAK1, JAK2, and TYK2 (IC50 >10 μ M). Ritlecitinib rapidly inactivates the JAK3 kinase, and blocks signaling and downstream STAT phosphorylation mediated by common gamma chain cytokines such as IL-2 and IL-15. Ritlecitinib can inhibit Th1/Th17 cell differentiation and function, and effectively suppress preclinical animal models such as alopecia areata, adjuvant-induced arthritis (AIA), and experimental autoimmune encephalomyelitis (EAE).
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Pimozide
0 ImagesPimozide is a dopamine receptor antagonist, with Kis of 1.4 nM, 2.5 nM and 588 nM for dopamine D2, D3 and D1 receptors, respectively, and also has affinity at α1-adrenoceptor, with a Ki of 39 nM; Pimozide also inhibits STAT3 and STAT5.
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AC-4-130
0 ImagesAC-4-130 is a potent STAT5 SH2 domain inhibitor. AC-4-130 directly binds to STAT5 and disrupts STAT5 activation, dimerization, nuclear translocation, and STAT5-dependent gene transcription. AC-4-130 induces cell cycle arrest and apoptosis in FLT3-ITD-driven leukemic cells. AC-4-130 has anti-cancer activity and can efficiently block pathological levels of STAT5 activity in acute myeloid leukemia (AML).
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INCA033989
0 ImagesCat. No.: HY-P991888Purity: 98.12%INCA033989 is a fully human IgG1 monoclonal antibody targeting mutCALR (KD = 1.75 nM for mutCALRdel52; KD = 6.78 nM for mutCALRins5). INCA033989 antagonizes mutCALR-driven signaling and proliferation. INCA033989 selectively inhibits pSTAT3/pSTAT5. INCA033989 prevents thrombocytosis and reduces the expansion of mutCALR-positive cells. INCA033989 is useful for research on myeloproliferative neoplasms .
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BCR-ABL degrader 1
0 ImagesCat. No.: HY-180798BCR-ABL degrader 1 is a hydrophobic tag degrader with GNF‑2 (HY-11007) as the ligand and Boc2His (HY-185595) as the hydrophobic tag. BCR-ABL degrader 1 mediates the degradation of BCR‑ABL with a DC50 of 19.9 μM. BCR-ABL degrader 1 induces the degradation of BCR-ABL fusion protein via the ubiquitin-proteasome pathway, a process involving Hsp70 and Hsp90. BCR-ABL degrader 1 downregulates p‑STAT5 and p‑SHP2, the downstream signaling molecules of BCR‑ABL. BCR-ABL degrader 1 can be used in the research of chronic myeloid leukemia.
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MA191
0 ImagesCat. No.: HY-175273MA191 is a FLT3 PROTAC degrader. MA191 targets and degrades mutant FLT3-ITD protein by recruiting the VHL E3 ligase in a manner dependent on ubiquitination and BIM, thereby blocking aberrant downstream MAPK/STAT5 signaling pathways and inducing apoptosis. MA191 can be used in research related to acute myeloid leukemia.
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AS2863619
0 ImagesAS2863619 is an orally active CDK8/19 inhibitor that also inhibits BMP2, MDA5 and RIG-I receptors. AS2863619 targets Stat5a-CDK8/19 to promote the differentiation of CD4+ T cells into regulatory T cells and induce FOXP3 expression, thereby restoring immune homeostasis and establishing transplant immune tolerance. AS2863619 also enhances the BMP2/SMAD signaling pathway to promote osteogenic differentiation and inhibit adipogenic differentiation. AS2863619 exerts osteoprotective effects by alleviating inflammation-induced impairment of osteogenic function and inducing neutrophil apoptosis (apoptosis). AS2863619 can be applied to research in related fields such as periodontitis-induced bone defects.
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AK-2292
0 ImagesAK-2292 is a potent and selective STAT5 PROTAC degrader, with a DC50 of 0.10 μM. AK-2292 induces degradation of STAT5A/B proteins in vitro and in vivo. AK-2292 can induce tumor regression in acute myeloid leukemia and chronic myeloid leukemia xenograft mouse models. AK-2292 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
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STAT4-IN-1
0 ImagesCat. No.: HY-173236Purity: 99.17%STAT4-IN-1 is an inhibitor of STAT4 with a Ki of 0.35 μM. STAT4-IN-1 is expected to be used in the research of autoimmune diseases, including inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, and diabetes.
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BD750
0 ImagesBD750, an effective immunosuppressant and a JAK3/STAT5 inhibitor, inhibits IL-2-induced JAK3/STAT5-dependent T cell proliferation, with IC50 values of 1.5 μM and 1.1 μM in mouse and human T cells, respectively.
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IST5-002
0 ImagesSynonyms: N6-Benzyladenosine-5'-phosphateIST5-002, 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).
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Stafib-1
0 ImagesStafib-1 is the first selective inhibitor of the STAT5b SH2 domain, with a Ki of 44 nM and an IC50 of 154 nM.
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GMB-475
0 ImagesGMB-475 is a potent BCR-ABL1 PROTAC based on Von Hippel-Lindau (VHL). GMB-475 targets the nutmeg pocket of ABL1 in an ectopic manner and degrades BCR-ABL1 protein through the ubiquitin proteasome pathway. GMB-475 inhibits the proliferation of human K562 cells and mouse Ba/F3 cells, and is used for the study of chronic myeloid leukemia.
