HP590
目录号 : GC67958HP590 是一种具有口服活性的、新型和强效的 STAT3 抑制剂 (STAT3 荧光素酶活性: IC50=27.8 nM; ATP 抑制: IC50=24.7 nM)。HP590 对胃癌细胞显示出抗增殖活性并可诱导细胞凋亡。
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
IC50: 27.8 nM (STAT3 luciferase activity)[1]
HP590 is an orally active, novel and potent STAT3 inhibitor (STAT3 luciferase activity: IC50=27.8 nM; ATP inhibition: IC50=24.7 nM). HP590 shows anti-proliferative activity to gastric cancer cells and induces apoptosis[1].
HP590 (0-40 μM; 72 h) shows anti-proliferative activities to MKN45, AGS, and MGC803 cells[1].
HP590 (0-40 nM; 0-24 h) inhibits STAT3 Tyr705 and Ser727 phosphorylation in GC cells, blocks the expression of STAT3 downstream genes (c-Myc and cyclin D1) in GC cells, reduces IL-6-mediated STAT3 nuclear translocation in MKN45 cells[1].
HP590 (5-20 nM; 48 h) induces gastric cancer cell apoptosis[1].
Cell Proliferation Assay[1]
| Cell Line: | MKN45, AGS, and MGC803 cells |
| Concentration: | 0-40 μM |
| Incubation Time: | 72 hours |
| Result: | Inhibited MKN45, AGS, and MGC803 cells with IC50s of 9.3, 13.5, and 8.7 nM, respectively. |
Apoptosis Analysis[1]
| Cell Line: | MKN45 and AGS cells |
| Concentration: | 5, 10, and 20 nM |
| Incubation Time: | 48 hours |
| Result: | Induced apoptosis in MKN45 and AGS cells in a dose-dependent manner. |
Western Blot Analysis[1]
| Cell Line: | Gastric Cancer Cells |
| Concentration: | 0-40 nM |
| Incubation Time: | 0-24 h |
| Result: | Inhibited STAT3 p-Tyr705 and p-Ser727 in GC cells completely at 40 nM. Blocked the expression of STAT3 downstream genes, including c-Myc and cyclin D1, in a concentration-dependent and time-dependent manner. Showed the STAT3 p-Tyr705 stimulated by IL-6 in GC cell lines, but entirely suppressed by HP590 at 40 nM. |
RT-PCR[1]
| Cell Line: | MKN45 and AGS cells |
| Concentration: | 10, 20, and 40 nM |
| Incubation Time: | 48 hours |
| Result: | Suppressed the expression of STAT3 downstream genes (c-Myc and cyclin D1) at the mRNA level. |
HP590 (oral administration; 25 and 50 mg/kg; once daily; 5 w) inhibits GC growth effectively by inhibiting the STAT3 activation and shows better tolerance in GC xenograft model[1].
| Animal Model: | BALB/c-nude mice injected with GC cells[1] |
| Dosage: | 25 and 50 mg/kg |
| Administration: | Oral administration; 25 and 50 mg/kg; once daily; 5 weeks |
| Result: | Inhibited MKN45 tumor growth in a concentration-dependent manner. Inhibited STAT3 phosphorylation at Tyr705 and Ser727 and reduced the expression of the downstream genes. Inhibited the expression of Ki67 (a proliferation marker). Showed no weight loss during HP590 treatment, and no apparent damage in the major organs of mice. |
[1]. He P, et al. Discovery of a Novel Potent STAT3 Inhibitor HP590 with Dual p-Tyr705/Ser727 Inhibitory Activity for Gastric Cancer Treatment. J Med Chem. 2022 Sep 14.
| Cas No. | SDF | Download SDF | |
| 分子式 | C29H24F6N4O3 | 分子量 | 590.52 |
| 溶解度 | 储存条件 | 4°C, away from moisture and light | |
| 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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.6934 mL | 8.4671 mL | 16.9342 mL |
| 5 mM | 0.3387 mL | 1.6934 mL | 3.3868 mL |
| 10 mM | 0.1693 mL | 0.8467 mL | 1.6934 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 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 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Discovery of a Novel Potent STAT3 Inhibitor HP590 with Dual p-Tyr705/Ser727 Inhibitory Activity for Gastric Cancer Treatment
J Med Chem 2022 Oct 13;65(19):12650-12674.PMID:36103247DOI:10.1021/acs.jmedchem.2c00413
Accumulating evidence has documented that STAT3 phosphorylation at Tyr705 and Ser727 jointly promotes the initiation and progression of gastric cancer. However, most reported STAT3 inhibitors have mainly focused on suppressing STAT3 phosphorylation at Tyr705 while ignoring the tumorigenic effects of phosphorylation at Ser727. Herein, we described the design, synthesis, and structure-activity relationship studies on a series of triaromatic heterocyclic derivatives as potent dual phosphorylation STAT3 inhibitors. These efforts led to the discovery of the best compound 3h (HP590) among the investigated ones, a novel, highly potent, and orally bioavailable STAT3 inhibitor possessing lower nanomolar inhibitory activity toward p-Tyr705 and p-Ser727. Target validation revealed that HP590 selectively targets STAT3 to remarkably inhibit its canonical and noncanonical activation and corresponding biological functions, thereby resulting in the growth inhibition of gastric cancer in vitro and in vivo, highlighting the therapeutic potential of dual phosphorylation STAT3 inhibitors for gastric cancer.