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Purity: ≥98%
BP-1-102 is a potent, orally bioavailable and selective STAT3 inhibitor, which binds Stat3 with an affinity Kd of 504 nM. BP-1-102 inhibits Stat3 DNA-binding activity in vitro, with an IC50 value of 6.8±0.8 μM. It blocks Stat3-phospho-tyrosine peptide interactions and Stat3 activation at 4-6.8 μM, and selectively inhibits growth, survival, migration, and invasion of Stat3-dependent tumor cells. BP-1-102-mediated inhibition of aberrantly active Stat3 in tumor cells suppresses the expression of c-Myc, Cyclin D1, Bcl-xL, Survivin, VEGF, and Krüppel-like factor 8.
| Targets |
BP-1-102 targets signal transducer and activator of transcription 3 (STAT3) (IC50 = 1.8 μM for STAT3 DNA-binding activity; IC50 = 2.2 μM for STAT3 phosphorylation inhibition) [1]
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| ln Vitro |
The affinity KD of BP-1-102 for Stat3 is 504 nM. In vitro, Stat3 DNA-binding activity is inhibited by BP-1-102, with an IC50 value of 6.8±0.8 μM. It specifically suppresses the growth, survival, migration, and invasion of tumor cells dependent on Stat3 and disrupts interactions between Stat3 and phospho-tyrosine peptides, as well as Stat3 activation at 4-6.8 μM. The suppression of aberrantly active Stat3 in tumor cells by BP-1-102 reduces the expression of Krüppel-like factor 8, c-Myc, Cyclin D1, Bcl-xL, Survivin, VEGF, and Cyclin D1[1].
In human breast cancer cell lines (MDA-MB-231, MCF-7, BT474) and lung cancer cell lines (A549, H1299), BP-1-102 (0.5–20 μM) inhibits cell proliferation in a dose-dependent manner, with IC50 values ranging from 2.5 to 5.8 μM. MDA-MB-231 (triple-negative breast cancer) and A549 (non-small cell lung cancer) cells show highest sensitivity (IC50 = 2.5–3.2 μM) [1] - It blocks STAT3 signaling: reduces phosphorylation of STAT3 (Tyr705) and STAT3 nuclear translocation (immunofluorescence), inhibits STAT3 DNA-binding activity (electrophoretic mobility shift assay, EMSA), and downregulates STAT3 target genes (Bcl-2, Survivin, Cyclin D1) at mRNA and protein levels (qRT-PCR and Western blot) [1] - In MDA-MB-231 cells, BP-1-102 (5 μM) induces apoptosis (Annexin V-FITC/PI staining shows apoptotic rate ~48%) and reduces colony formation (colony number reduced by ~70% vs. control) [1] - In human colorectal cancer cell lines (HT-29, HCT116) stimulated with IL-6 (20 ng/mL) + TNF-α (10 ng/mL), BP-1-102 (1–10 μM) dose-dependently inhibits cell proliferation (IC50 = 3.6 μM for HT-29; IC50 = 4.1 μM for HCT116) and STAT3 phosphorylation (Tyr705) (Western blot). It also blocks synergistic activation of NF-κB (p65 phosphorylation) induced by IL-6 + TNF-α [2] |
| ln Vivo |
Mice therapeutically fed BP-1-102, an orally accessible drug targeting STAT3/NF-kB activation and cross-talk, exhibit reduced colon carcinogenesis and diminished production of STAT3/NF-kB-activating cytokines in the neoplastic areas[2]. BP -1-102 is orally accessible and that the drug accumulates in tumor tissues at levels adequate to inhibit aberrantly active Stat3 actions and decrease tumor growth[1].
In a subcutaneous xenograft model of triple-negative breast cancer (MDA-MB-231 cells in nude mice), oral administration of BP-1-102 (50 mg/kg/day) for 21 days inhibits tumor growth by ~68% compared to vehicle control. Median survival of mice is prolonged from 35 days (control) to 62 days [1] - In a subcutaneous xenograft model of non-small cell lung cancer (A549 cells in nude mice), oral BP-1-102 (50 mg/kg/day) for 24 days reduces tumor volume by ~72% and tumor weight by ~65%. Tumor tissues show reduced p-STAT3 (Tyr705), Bcl-2, and Ki-67 expression, and increased cleaved caspase-3 levels (immunohistochemistry and Western blot) [1] |
| Enzyme Assay |
STAT3 DNA-binding activity assay: Recombinant human STAT3 protein (2 μM) was incubated with biotin-labeled STAT3-responsive DNA probe and reaction buffer (20 mM Tris-HCl pH 7.5, 100 mM NaCl, 1 mM DTT, 5% glycerol) at room temperature for 30 minutes. BP-1-102 (0.1–10 μM) was added before probe incubation. DNA-protein complexes were separated by non-denaturing PAGE, transferred to a membrane, and detected with streptavidin-horseradish peroxidase. Inhibition rate was calculated by densitometric analysis, and IC50 was determined [1]
- STAT3 phosphorylation inhibition assay: MDA-MB-231 cells were serum-starved for 16 hours, pretreated with BP-1-102 (0.5–20 μM) for 2 hours, then stimulated with IL-6 (20 ng/mL) for 30 minutes. Cells were lysed, and p-STAT3 (Tyr705) levels were measured by Western blot. IC50 was calculated based on the dose-response curve of p-STAT3 inhibition [1] |
| Cell Assay |
Breast/lung cancer cell proliferation and signaling assay: MDA-MB-231/A549/MCF-7 cells (5×10³ per well) were seeded in 96-well plates, treated with BP-1-102 (0.5–20 μM) for 48 hours. Cell viability was measured by MTT assay to determine IC50. For signaling analysis, cells were treated with the drug (5–10 μM) for 24 hours, lysed, and Western blot detected p-STAT3, STAT3, Bcl-2, Survivin, Cyclin D1, and GAPDH [1]
- Apoptosis and clonogenic assay: MDA-MB-231 cells (1×10⁵ per well for apoptosis; 1×10³ per well for clonogenic) were seeded in 6-well plates. For apoptosis, cells were treated with BP-1-102 (5 μM) for 24 hours, stained with Annexin V-FITC/PI, and analyzed by flow cytometry. For clonogenic assay, cells were treated with the drug (1–5 μM) for 14 days (medium changed every 3 days), stained with crystal violet, and colonies with >50 cells were counted [1] - Colorectal cancer cell proliferation assay: HT-29/HCT116 cells (5×10³ per well) were seeded in 96-well plates, pretreated with BP-1-102 (1–10 μM) for 1 hour, then stimulated with IL-6 (20 ng/mL) + TNF-α (10 ng/mL) for 48 hours. Cell viability was measured by CCK-8 assay. Western blot analyzed p-STAT3 (Tyr705), STAT3, p-p65 (NF-κB), and GAPDH [2] |
| Animal Protocol |
BP-1-102 dissolved in 0.05% DMSO in water; 1 or 3mg/kg (i.v.) every 2 or every 3 d or 3 mg/kg (oral gavage, 100 μL) every day for 15 or 20 d.
Athymic nude mice with established tumors Triple-negative breast cancer xenograft model: Nude mice (4-week-old, female) were subcutaneously injected with MDA-MB-231 cells (5×10⁶ cells/mouse) into the right flank. When tumors reached ~120 mm³, mice were randomized into control (n = 6) and BP-1-102 treatment (n = 6) groups. The drug was dissolved in DMSO (5%) + 0.5% carboxymethylcellulose (CMC) + 0.1% Tween 80, administered orally at 50 mg/kg once daily for 21 days. Tumor volume (length×width²/2) and body weight were measured every 3 days; survival time was recorded [1] - Non-small cell lung cancer xenograft model: Nude mice (4-week-old, male) were subcutaneously injected with A549 cells (5×10⁶ cells/mouse). When tumors reached ~100 mm³, mice were divided into control (n = 6) and treatment (n = 6) groups. BP-1-102 was administered orally at 50 mg/kg once daily for 24 days. Tumor volume and body weight were measured every 3 days; tumors were excised for immunohistochemistry and Western blot [1] |
| ADME/Pharmacokinetics |
Oral bioavailability: 45% in rats (measured by comparing plasma concentrations after oral and intravenous administration of 20 mg/kg) [1] - Plasma half-life (t1/2): 2.8 hours in rats [1] - Plasma protein binding: 89% in human plasma and 87% in rat plasma (equilibrium dialysis test) [1] - Tissue distribution: The highest concentrations were found in the liver (2.3 times that of plasma), lung (2.1 times that of plasma), and tumor tissue (1.9 times that of plasma) in rats; the permeability to the central nervous system was extremely low (<1.2% of plasma concentration) [1] - Metabolism: Mainly metabolized by hydroxylation mediated by hepatic CYP2C9 and CYP3A4; no major active metabolites were found [1] - Excretion: Within 72 hours after administration to rats, 52% was excreted in feces and 38% in urine [1]
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| Toxicity/Toxicokinetics |
In vitro toxicity: BP-1-102 at concentrations up to 20 μM showed no significant cytotoxicity to normal human mammary epithelial cells (HMEC) or lung fibroblasts (MRC-5) (cell viability >85% vs. control group) [1] - Acute toxicity: LD50 in rats and mice >1000 mg/kg (oral administration); no death or serious toxic symptoms (drowsiness, convulsions) were observed at doses up to 1000 mg/kg [1] - Repeated-dose toxicity: In a 28-day rat study (oral doses of 25, 50 and 100 mg/kg/day, respectively), the drug was well tolerated. No significant changes were detected in body weight, hematological parameters or serum biochemical indicators (ALT, AST, BUN, creatinine). Histological examination of the liver, kidneys, heart and lungs revealed no abnormal lesions [1]
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| References |
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| Additional Infomation |
BP-1-102 is a small molecule inhibitor of STAT3 with high oral bioavailability[1]. Its mechanism of action includes binding to the SH2 domain of STAT3, inhibiting STAT3 dimerization and nuclear translocation, thereby blocking the transcription of STAT3-mediated oncogenes (Bcl-2, Survivin, Cyclin D1)[1]. In colorectal cancer cells, BP-1-102 eliminates the synergistic activation of STAT3 and NF-κB by IL-6/TNF-α, inhibiting cell proliferation driven by pro-inflammatory cytokines[2]. Preclinical efficacy in breast cancer, lung cancer, and colorectal cancer models supports its potential as a therapeutic agent for STAT3-activated solid tumors[1,2]. BP-1-102 has good oral bioavailability and low toxicity, making it suitable for oral administration in a clinical setting[1].
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| Molecular Formula |
C29H27F5N2O6S
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| Molecular Weight |
626.59
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| Exact Mass |
626.151
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| CAS # |
1334493-07-0
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| Related CAS # |
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| PubChem CID |
53388144
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
749.2±70.0 °C at 760 mmHg
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| Flash Point |
406.9±35.7 °C
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| Vapour Pressure |
0.0±2.6 mmHg at 25°C
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| Index of Refraction |
1.601
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| LogP |
7.77
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
43
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| Complexity |
1050
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
WNVSFFVDMUSXSX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H27F5N2O6S/c1-35(43(41,42)28-26(33)24(31)23(30)25(32)27(28)34)15-22(38)36(19-11-12-20(29(39)40)21(37)13-19)14-16-7-9-18(10-8-16)17-5-3-2-4-6-17/h7-13,17,37H,2-6,14-15H2,1H3,(H,39,40)
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| Chemical Name |
4-[(4-cyclohexylphenyl)methyl-[2-[methyl-(2,3,4,5,6-pentafluorophenyl)sulfonylamino]acetyl]amino]-2-hydroxybenzoic acid
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.99 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 25.0 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: ≥ 2.5 mg/mL (3.99 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5959 mL | 7.9797 mL | 15.9594 mL | |
| 5 mM | 0.3192 mL | 1.5959 mL | 3.1919 mL | |
| 10 mM | 0.1596 mL | 0.7980 mL | 1.5959 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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