STAT5-IN-1 is a cell-permeable STAT5 inhibitor with an IC50 value of 47μM against the STAT5β isoform. STAT5-IN-1 blocks STAT5 signaling and STAT5-DNA binding by interacting with the SH2 domain of STAT5. STAT5-IN-1 selectively inhibits STAT5 and downregulates C/EBPβ and Acod1 expression. STAT5-IN-1 can be used in studies related to tumors, hematological diseases, and immunology[1-4].
In vitro, treatment of CD103+ cDC1 cells with 0-50μM STAT5-IN-1 for 9 days increased the proportion of Annexin V+7AAD- cells[5]. Treatment of TF-1(R140Q) cells with 25-100μM STAT5-IN-1 for 3 days blocked cytokine-independent proliferation in a concentration-dependent manner[6]. Treatment of NK cells with 100μM STAT5-IN-1 for 6 hours reduced p-S6Ser235/236 levels[7].
In vivo, oral administration of 10mg/kg STAT5-IN-1 every other day to high-fat diet-fed ApoE-/- mice for 12 weeks reduced atherosclerotic plaque area in the aortic arch and aortic root. STAT5-IN-1 decreased aortic ICAM-1, VCAM-1, TNF-α, and IL-6 mRNA levels and reduced aortic TNF-α and IL-6 protein levels[8]. Intraperitoneal injection of 20mg/kg STAT5-IN-1 every three days to MC38 colon adenocarcinoma-bearing Rig-I-/- mice for 22 consecutive days restored tumor growth[9].
References:
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[2] Chen S, Lu H, Ying Y, et al. IL2RG knockout mitigates polycystic ovary syndrome pathogenesis by transitioning pyroptosis to apoptosis through the GSDME pathway. Journal of Ovarian Research. 2025 Aug 19;18:189.
[3] Zhu F, Chen H, Xu M, et al. Cryptotanshinone possesses therapeutic effects on ischaemic stroke through regulating STAT5 in a rat model. Pharmaceutical Biology. 2021;59(1):465-471.
[4] Yovas A, Stanely SP, Issac R, et al. β-caryophyllene blocks reactive oxygen species-mediated hyperlipidemia in isoproterenol-induced myocardial infarcted rats. Eur J Pharmacol. 2023 Dec 5;960:176102.
[5] Xu F, Liu C, Dong Y, et al. Ablation of Cbl-b and c-Cbl in dendritic cells causes spontaneous liver cirrhosis via altering multiple properties of CD103+ cDC1s. Cell Death Discovery. 2022;8:142.
[6] Yang J, Chen J, Chang J, et al. IDH2/R140Q mutation confers cytokine-independent proliferation of TF-1 cells by activating constitutive STAT3/5 phosphorylation. Cell Commun Signal. 2024 Feb 12;22:116.
[7] Wang F, Meng M, Mo B, et al. Crosstalks between mTORC1 and mTORC2 variagate cytokine signaling to control NK maturation and effector function. Nat Commun. 2018 Nov 19;9:4874.
[8] Wang X, Ding X, Yan J, et al. STAT5 inhibitor attenuates atherosclerosis via inhibition of inflammation: the role of STAT5 in atherosclerosis. Am J Transl Res. 2021;13(3):1422-1431.
[9] Jiang X, Lin J, Shangguan C, et al. Intrinsic RIG-I restrains STAT5 activation to modulate antitumor activity of CD8+ T cells. J Clin Invest. 2023;133(9):e160790.