WP1066
(Synonyms: (2E)-3-(6-溴-2-吡啶基)-2-氰基-N-[(1S)-1-苯基乙基]-2-丙烯酰胺) 目录号 : GC15980
WP1066是一种STAT3（信号转导和转录激活因子3）可逆的竞争性抑制剂，针对STAT3 Tyr705位点磷酸化的抑制IC50约为2.5μM，通常用于恶性肿瘤及炎症相关疾病的研究。
Cas No.:857064-38-1
Sample solution is provided at 25 µL, 10mM.
WP1066 is a reversible competitive inhibitor of STAT3 (Signal Transducer and Activator of Transcription 3), with an IC50 of approximately 2.5µM for the inhibition of STAT3 Tyr705 phosphorylation[1]. WP1066 is commonly used in the research of malignant tumors (such as glioma, hepatocellular carcinoma, and breast cancer) and inflammation-related diseases[2]. WP1066 specifically occupies the SH2 domain pocket of STAT3 through hydrogen bonds and hydrophobic interactions. Its binding can directly block the dimerization process of STAT3[3], thereby inhibiting its nuclear translocation and the transcriptional activation of downstream target genes. This ultimately suppresses tumor cell proliferation, induces tumor cell apoptosis, and reduces the release of inflammatory factors[4].
In vitro, pre-treatment of human oral squamous cell carcinoma Tca8113 and Tca8113/DDP cells with WP1066 (5µM) for 24 hours, followed by treatment with cisplatin (DDP, 0.1–16mg/ml) for 48 hours, significantly inhibits cell proliferation, migration, and invasion capabilities, while reducing STAT3 phosphorylation and miR-21 expression[5]. Treatment of STSW-01 and STSW-01-LUC cells with WP1066 (1.5–3.0µM) for 24 hours significantly decreases STAT3 phosphorylation levels and induces the expression of cell death markers, including necrosis-related protein pMLKL (Ser358) and apoptosis-related protein caspase 3/7[6].
In vivo, WP1066 (40mg/kg) is administered locally, three times per week, to treat a TSCCA xenograft nude mouse model. WP1066 significantly inhibits the increase in tumor volume, reduces tumor cell proliferation and invasion capabilities, and induces tumor cell apoptosis[7]. WP1066 (10–20mg/kg) is administered intraperitoneally, three times per week, to treat gp130757FF mice from 8 weeks of age until 10 weeks of age. WP1066 significantly reduces gastric tumor volume, decreases tumor cell proliferation, and increases tumor cell apoptosis[8].
References:
[1] Horiguchi A, Asano T, Kuroda K, et al. STAT3 inhibitor WP1066 as a novel therapeutic agent for renal cell carcinoma. Br J Cancer. 2010 May 25;102(11):1592-9.
[2] Yang J, Li N, Zhao X, et al. WP1066, a small molecule inhibitor of STAT3, chemosensitizes paclitaxel-resistant ovarian cancer cells to paclitaxel by simultaneously inhibiting the activity of STAT3 and the interaction of STAT3 with Stathmin. Biochem Pharmacol. 2024 Mar;221:116040.
[3] Tsurumaki H, Katano H, Sato K, et al. WP1066, a small molecule inhibitor of the JAK/STAT3 pathway, inhibits ceramide glucosyltransferase activity. Biochem Biophys Res Commun. 2017 Sep 16;491(2):265-270.
[4] Tsujita Y, Horiguchi A, Tasaki S, et al. STAT3 inhibition by WP1066 suppresses the growth and invasiveness of bladder cancer cells. Oncol Rep. 2017 Oct;38(4):2197-2204.
[5] Zhou X, Ren Y, Liu A, et al. WP1066 sensitizes oral squamous cell carcinoma cells to cisplatin by targeting STAT3/miR-21 axis. Sci Rep. 2014 Dec 17;4:7461.
[6] Allaf A, Victoria B, Rosario R, et al. WP1066 induces cell death in a schwannomatosis patient-derived schwannoma cell line. Cold Spring Harb Mol Case Stud. 2022 Jun 22;8(4):a006178.
[7] Zhou X, Ren Y, Liu A, et al. STAT3 inhibitor WP1066 attenuates miRNA-21 to suppress human oral squamous cell carcinoma growth in vitro and in vivo. Oncol Rep. 2014 May;31(5):2173-80.
[8] Judd LM, Menheniott TR, Ling H, et al. Inhibition of the JAK2/STAT3 pathway reduces gastric cancer growth in vitro and in vivo. PLoS One. 2014 May 7;9(5):e95993.
WP1066是一种STAT3（信号转导和转录激活因子3）可逆的竞争性抑制剂，针对STAT3 Tyr705位点磷酸化的抑制IC50约为2.5μM[1]，通常用于恶性肿瘤及炎症相关疾病的研究[2]。WP1066 通过氢键和疏水相互作用，特异性占据STAT3的SH2结构域口袋，WP1066的结合可直接阻断STAT3的二聚化过程[3]，进而抑制其核转位及下游靶基因的转录激活，最终抑制肿瘤细胞增殖、诱导肿瘤细胞凋亡，并减少炎症因子的释放[4]。
在体外，WP1066（5µM）预处理人口腔鳞癌Tca8113和Tca8113/DDP细胞48h，随后以顺铂（DDP，0.1–16mg/ml）处理48h，WP1066显著抑制细胞增殖、迁移和侵袭能力，同时降低STAT3磷酸化和miR-21的表达[5]。WP1066（1.5–3.0µM）处理STSW-01及STSW-01-LUC细胞24h，显著降低STAT3磷酸化水平，同时诱导细胞死亡标志物的表达，包括坏死相关蛋白pMLKL（Ser358）和凋亡相关蛋白caspase 3/7[6]。
在体内，WP1066（40mg/kg）局部注射，每周三次，用于处理TSCCA异种移植裸鼠模型。WP1066显著抑制了肿瘤体积的增加，减少了肿瘤细胞的增殖和侵袭能力，同时诱导了肿瘤细胞凋亡[7]。WP1066（10–20mg/kg）腹腔注射，每周三次，用于处理8周龄开始直至10周龄的gp130757FF小鼠。WP1066显著减少了胃肿瘤体积，降低了肿瘤细胞的增殖，同时增加了肿瘤细胞的凋亡[8]。
| Cell experiment [1]: | |
Cell lines | STSW-01 cells (human schwannoma cell line derived from a schwannomatosis patient) |
Preparation Method | STSW-01 cells were cultured in Schwann cell media (SCM) containing HEPES buffer and bicarbonate buffered basal medium with 5% FBS, penicillin/streptomycin, and a proprietary supplement mix. Cells were maintained at 37°C with 5% CO₂. Cells were treated with WP1066 at a concentration of 1.5–3.0µM for 24 hours. |
Reaction Conditions | 1.5–3.0µM; 24 hours |
Applications | WP1066 significantly reduced cell viability and STAT-3 phosphorylation in STSW-01 cells. WP1066 also induced expression of markers for both necroptosis (pMLKL) and caspase-dependent cell death (cleaved caspase 3/7) |
| Animal experiment [2]: | |
Animal models | Nude mice |
Preparation Method | Nude mice were subcutaneously implanted with TSCCA cells to establish a xenograft tumor model. When tumors reached approximately 10mm in length, mice were divided into three groups: control, DMSO-treated (local injection, once every 3 days for 21 days), and WP1066-treated (40mg/kg, local injection) |
Dosage form | 40mg/kg; local injection |
Applications | WP1066 treatment significantly reduced tumor volume compared to control and DMSO-treated groups. Histological analysis showed decreased microvessel density, chromatin staining, and increased apoptotic nuclei in WP1066-treated tumors. Expressions of STAT3, p-STAT3, Ki67, Bcl-2, and MMP-2 were downregulated, while PTEN, PDCD4, and TIMP-3 were upregulated in WP1066-treated tumors. |
References: | |
| Cas No. | 857064-38-1 | SDF | |
| 别名 | (2E)-3-(6-溴-2-吡啶基)-2-氰基-N-[(1S)-1-苯基乙基]-2-丙烯酰胺 | ||
| 化学名 | (E)-3-(6-bromopyridin-2-yl)-2-cyano-N-[(1S)-1-phenylethyl]prop-2-enamide | ||
| Canonical SMILES | CC(C1=CC=CC=C1)NC(=O)C(=CC2=NC(=CC=C2)Br)C#N | ||
| 分子式 | C17H14BrN3O | 分子量 | 356.22 |
| 溶解度 | ≥ 17.8 mg/mL in DMSO, ≥ 24.6 mg/mL in EtOH with ultrasonic and warming | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.8073 mL | 14.0363 mL | 28.0725 mL |
| 5 mM | 0.5615 mL | 2.8073 mL | 5.6145 mL |
| 10 mM | 0.2807 mL | 1.4036 mL | 2.8073 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
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2.
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