SH-4-54 is a specific STAT3 inhibitor with a KD of 300 nM[1]. It is commonly used in the study of treatments for brain cancers such as glioblastoma[2-3].
SH-4-54 demonstrates potent cytotoxic effects on tumor cells with aberrantly active STAT3, exhibiting an IC50 range of 1.0-2.7μM for glioma U251MG and U87MG cells[3]. SH-4-54 (16μM; 72h) effectively induces apoptosis in temozolomide-resistant glioblastoma multiforme cells by mitoSTAT3 pathway, leading to disrupted oxidative phosphorylation and negative regulation of mitochondrial-encoded genes[4]. In addition, SH-4-54 reduces cell survival and phosphorylated STAT3 levels in various tumors, including bladder cancer and pancreatic cancer[5-6].
SH-4-54 (6 mg/kg; every 2 or 3 days; intravenous administration) effectively blocked the DNA binding activity of STAT3, leading to the inhibition of STAT3-dependent gene transcription in human glioma, breast, and prostate cancer cells, as well as in v-Src-transformed murine fibroblasts. And effectively suppressed tumor growth in mouse xenograft models of glioma and breast cancer [3].
References:
[1]. Haftchenary S, Luchman HA, Jouk AO, et al. Potent Targeting of the STAT3 Protein in Brain Cancer Stem Cells: A Promising Route for Treating Glioblastoma. ACS Med Chem Lett. 2013 Sep 8;4(11):1102-7.
[2]. Yu D, Wang S, Wang J, et al. EZH2-STAT3 signaling pathway regulates GSDMD-mediated pyroptosis in glioblastoma. Cell Death Discov. 2024 Jul 28;10(1):341.
[3]. Yue P, Lopez-Tapia F, Paladino D, et al. Hydroxamic Acid and Benzoic Acid-Based STAT3 Inhibitors Suppress Human Glioma and Breast Cancer Phenotypes In Vitro and In Vivo. Cancer Res. 2016 Feb 1;76(3):652-63.
[4]. Cui P, Wei F, Hou J, et al. STAT3 inhibition induced temozolomide-resistant glioblastoma apoptosis via triggering mitochondrial STAT3 translocation and respiratory chain dysfunction. Cell Signal. 2020 Jul;71:109598.
[5]. Hindupur SV, Schmid SC, Koch JA, et al. STAT3/5 Inhibitors Suppress Proliferation in Bladder Cancer and Enhance Oncolytic Adenovirus Therapy. Int J Mol Sci. 2020 Feb 7;21(3):1106.
[6]. Arpin CC, Mac S, Jiang Y, et al. Applying Small Molecule Signal Transducer and Activator of Transcription-3 (STAT3) Protein Inhibitors as Pancreatic Cancer Therapeutics. Mol Cancer Ther. 2016 May;15(5):794-805.
SH-4-54 是一种特异性 STAT3 抑制剂，KD为 300 nM[1]。通常用于研究胶质母细胞瘤等脑癌的治疗[2-3]。
SH-4-54 对于 STAT3 异常活跃的肿瘤细胞表现出强大的细胞毒性，其对胶质瘤 U251MG 和 U87MG 细胞的 IC50 范围为 1.0-2.7 μM[3]。SH-4-54 (16μM; 72h) 通过 mitoSTAT3 通路有效诱导耐替莫唑胺的多形性胶质母细胞瘤细胞凋亡，导致氧化磷酸化受损及线粒体编码基因的负调控[4]。此外，SH-4-54 在多种肿瘤中（包括膀胱癌、胰腺癌）降低细胞存活率和磷酸化的 STAT3 水平，促进细胞凋亡[5-6]。
SH-4-54（6mg/kg; every 2 or 3 days; intravenous administration）有效阻断了STAT3的DNA结合活性，导致人类胶质瘤、乳腺癌和前列腺癌细胞以及v-Src转化的小鼠成纤维细胞中STAT3依赖的基因转录被抑制，在小鼠异种移植模型中有效抑制了胶质瘤和乳腺癌的肿瘤生长[3]。