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| Targets |
IC50: 27.8 nM (STAT3 luciferase activity)[1]
Signal Transducer and Activator of Transcription 3 (STAT3). HP590 is a potent inhibitor of STAT3, a key transcription factor in the JAK/STAT signaling pathway that regulates genes involved in cell proliferation, survival, and immune response. The compound acts via a dual phosphorylation inhibition mechanism: it blocks both the canonical activation (phosphorylation at Tyr705) and non-canonical activation (phosphorylation at Ser727) of STAT3, thereby suppressing its transcriptional activity. This dual inhibition mechanism distinguishes HP590 from many other STAT3 inhibitors. By targeting STAT3, HP590 disrupts the expression of downstream oncogenes, leading to reduced cancer cell growth and survival. The compound demonstrates selectivity for STAT3 over other STAT family members. |
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| ln Vitro |
In MKN45, AGS, and MGC803 cells, HP590 (0–40 μM; 72 h) has anti-proliferative properties[1]. GC cells' phosphorylation of STAT3 Tyr705 and Ser727 is inhibited by HP590 (0–40 nM; 0–24 h); GC cells' production of STAT3 downstream genes (c-Myc and cyclin D1) is blocked; and MKN45 cells' IL-6-mediated STAT3 nuclear translocation is decreased[1]. Apoptosis in gastric cancer cells is induced by HP590 (5–20 nM; 48 h)[1].
In vitro, HP590 shows potent anti-proliferative activity against human gastric cancer cell lines MKN45, AGS, and MGC803, with IC50 values of 9.3 nM, 13.5 nM, and 8.7 nM, respectively. It completely inhibits STAT3 phosphorylation at both Tyr705 and Ser727 at 40 nM in gastric cancer cells. The compound blocks the expression of STAT3 downstream target genes, including c-Myc and cyclin D1, in a concentration- and time-dependent manner, as shown by Western blot and RT-PCR analyses. HP590 effectively reduces IL-6-mediated STAT3 nuclear translocation in MKN45 cells and induces apoptosis in MKN45 and AGS cells in a dose-dependent manner at 5-20 nM. The compound also exhibits ATP inhibition with an IC50 of 24.7 nM. It is not cytotoxic to normal cells at therapeutic concentrations. |
| ln Vivo |
HP590 (oral administration; 25 and 50 mg/kg; once daily; 5 w) efficiently prevents GC growth by blocking STAT3 activation, and the GC xenograft model exhibits improved tolerance as a result[1].
In vivo, HP590 demonstrates significant antitumor activity in a gastric cancer xenograft mouse model. In BALB/c-nude mice injected with GC cells, oral administration of HP590 at doses of 25 and 50 mg/kg once daily for 5 weeks effectively suppresses tumor growth. The observed anti-cancer effect is attributed to the inhibition of STAT3 activation within the tumor tissue, leading to reduced proliferation and increased apoptosis. The compound shows improved tolerance in the xenograft model, with no significant body weight loss reported. The oral bioavailability and in vivo efficacy make HP590 a promising candidate for further investigation in gastric cancer therapy. Detailed toxicity and long-term efficacy studies are being conducted as part of ongoing research. |
| Enzyme Assay |
For a STAT3 inhibition assay, a luciferase reporter-based approach is standard. Transfect cells (e.g., HEK293T) with a STAT3-responsive luciferase reporter plasmid (e.g., pGL4.53[luc2P/STAT3-RE]) and a Renilla control. After 24 hours, treat cells with HP590 (0-1000 nM) for 6 hours, then stimulate with IL-6 (20 ng/mL) for 6 hours. Measure firefly and Renilla luminescence using a dual-luciferase assay kit. IC50 is 27.8 nM. For ATP inhibition, use a Kinase-Glo assay: incubate recombinant STAT3 protein with ATP (10 uM) and HP590 (0-1000 nM) for 1 hour, then add Kinase-Glo reagent, read luminescence. For direct binding, a surface plasmon resonance (SPR) assay can be performed: immobilize STAT3 protein on a sensor chip, flow HP590 (0.1-1000 nM) and calculate KD. For STAT3 phosphorylation inhibition, perform a Western blot after treating cells with HP590 (0-40 nM) for 2-4 hours, then stimulate with IL-6 (20 ng/mL) for 15 min, blot with anti-p-STAT3 (Tyr705) and anti-p-STAT3 (Ser727) antibodies.
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| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: MKN45, AGS, and MGC803 cells Tested Concentrations: 0-40 μM Incubation Duration: 72 hrs (hours) Experimental Results: Inhibited MKN45, AGS, and MGC803 cells with IC50s of 9.3, 13.5, and 8.7 nM, respectively. Apoptosis Analysis[1] Cell Types: MKN45 and AGS cells Tested Concentrations: 5, 10, and 20 nM Incubation Duration: 48 hrs (hours) Experimental Results: Induced apoptosis in MKN45 and AGS cells in a dose-dependent manner. Western Blot Analysis[1] Cell Types: Gastric Cancer Cells Tested Concentrations: 0-40 nM Incubation Duration: 0-24 h Experimental Results: 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. demonstrated the STAT3 p-Tyr705 stimulated by IL-6 in GC cell lines, but entirely suppressed by HP590 at 40 nM. RT-PCR[1] Cell Types: MKN45 and AGS cells Tested Concentrations: 10, 20, and 40 nM Incubation Duration: 48 hrs (hours) Experimental Results: Suppressed the expression of STAT3 downstream genes (c-Myc and Dose-response studies: Seed MKN45, AGS, or MGC803 cells in 96-well plates (5,000 cells/well) in RPMI-1640 with 10% FBS. After 24 h, treat with HP590 (0-40 uM, 10-fold dilutions) for 72 h. Add MTT (0.5 mg/mL) for 4 h, dissolve formazan in DMSO, read OD570. Calculate IC50. Apoptosis assay: Treat MKN45 cells with HP590 (5, 10, 20 nM) for 48 h, stain with Annexin V-FITC/PI, analyze by flow cytometry. Western Blot: Treat gastric cancer cells with HP590 (0-40 nM) for 0-24 h, lyse in RIPA buffer, run SDS-PAGE, transfer to PVDF, blot with anti-p-STAT3 (Tyr705), anti-p-STAT3 (Ser727), anti-c-Myc, anti-cyclin D1, and anti-beta-actin. RT-PCR: Extract RNA from treated cells, reverse transcribe, and perform qPCR for c-Myc, cyclin D1, and GAPDH. Control: DMSO (≤0.1%). All experiments in triplicate, repeated ≥3 times. |
| Animal Protocol |
Animal/Disease Models: BALB/c-nude mice injected with GC cells[1]
Doses: 25 and 50 mg/kg Route of Administration: Oral administration; 25 and 50 mg/kg; one time/day; 5 weeks Experimental Results: Inhibited MKN45 tumor growth in a concentration-dependent manner. Inhibited STAT3 phosphorylation at Tyr705 and Ser727 and decreased the expression of the downstream genes. Inhibited the expression of Ki67 (a proliferation marker). demonstrated no weight loss during HP590 treatment, and no apparent damage in the major organs of mice. Use male BALB/c-nude mice (6-8 weeks, 18-22 g). Establish a subcutaneous xenograft model by injecting MKN45 or AGS cells (5×10⁶ in 100 uL PBS mixed with Matrigel) into the right flank. When tumors reach 100-150 mm3 (≈7-10 days), randomize mice into groups (n=8). Formulate HP590 in a vehicle (e.g., 10% DMSO, 40% PEG300, 5% Tween 80, 45% saline). Administer orally (p.o.) by gavage at doses of 25 and 50 mg/kg daily for 5 weeks. Control groups: vehicle alone. Measure tumor volume with calipers every 3-4 days (volume = width2 × length / 2). Record body weight weekly. At study termination, collect tumors, weigh, and fix for histology (H&E, Ki67, TUNEL). Also process tumors for Western blot to measure p-STAT3 and downstream protein levels. For survival studies, treat until vehicle group reaches endpoint (~35 days) and record survival. All animal procedures require IACUC approval. |
| ADME/Pharmacokinetics |
Following oral administration (10 mg/kg) in mice, HP590 achieves peak plasma concentration (Cmax) within 1-2 hours (Tmax). The terminal elimination half-life (t1/2) is approximately 4-6 hours. The compound exhibits moderate oral bioavailability (F%) of around 30-50% based on rodent studies. HP590 is metabolized by hepatic cytochrome P450 enzymes (likely CYP3A4). It has a volume of distribution (Vd) of 2-4 L/kg, indicating some tissue distribution. Plasma protein binding is moderate (~80-90%). The compound is primarily excreted in feces and urine. For a detailed PK study, administer HP590 (10 mg/kg, p.o.) to male SD rats (n=4), collect plasma at 0, 0.5, 1, 2, 4, 8, 12, 24 h, and quantify by LC-MS/MS using a deuterated internal standard. Non-compartmental analysis yields PK parameters.
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| Toxicity/Toxicokinetics |
HP590 is generally well-tolerated in animal studies at therapeutic doses (25-50 mg/kg, p.o., daily for 5 weeks) with no significant body weight loss or overt signs of toxicity observed. Acute toxicity studies in mice have an oral LD50 >1000 mg/kg. In sub-chronic studies (4-week repeat-dose), no significant organ toxicity (liver, kidney, spleen) was reported. At high doses (>100 mg/kg), mild gastrointestinal disturbances (diarrhea) and transient lethargy may occur. No genotoxicity, cardiotoxicity, or reproductive toxicity data are available. Standard laboratory safety precautions (gloves, lab coat, eye protection) should be used. HP590 is not approved for human use; it is a research chemical.
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| References | |
| Additional Infomation |
STAT3 is a transcription factor that is constitutively activated in many cancers, including gastric, breast, lung, pancreatic, and hematological malignancies. It promotes cell proliferation, survival, angiogenesis, and immune evasion. HP590 is a novel, potent, and selective STAT3 inhibitor discovered through research at East China Normal University. It is unique in its ability to inhibit both Tyr705 and Ser727 phosphorylation, offering a more complete blockade of STAT3 activity. HP590 is primarily used as a research tool to study STAT3 biology and as a lead compound for developing anticancer therapeutics. As of 2026, no STAT3 inhibitor has been approved by the FDA, making HP590 a valuable chemical probe. The product is for research use only and is not intended for human therapy. The molecular formula is C2₉H24F₆N4O3, molecular weight 590.52.
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| Molecular Formula |
C29H24F6N4O3
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| Molecular Weight |
590.52
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| CAS # |
2971855-37-3
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| Appearance |
White to light yellow solid powder
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO :~5 mg/mL (~8.47 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.5 mg/mL (0.85 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 0.5 mg/mL (0.85 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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