BP-1-102
目录号 : GC34063
A STAT3 inhibitor
Cas No.:1334493-07-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | Proliferating cells in 6- or 96-well plates are treated once with 0-30 μM BP-1-102 for 24 h or with 10 μM BP-1-102 for up to 96 h. Viable cells are counted by trypan blue exclusion/phase-contrast microscopy or assessed by a cell proliferation kit[1]. |
Animal experiment: | Mice: Athymic nude mice with established tumors are grouped and then given BP-1-102 (in 0.05% DMSO in water) at 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. Animals are monitored every day, and tumor sizes are measured with calipers and body weights are taken every 2 or 3 d. For each treatment group, the tumor volumes for each set of measurements are statistically analyzed in comparison with the control group using a paired T test[1]. |
References: [1]. Zhang X, et al. Orally bioavailable small-molecule inhibitor of transcription factor Stat3 regresses human breast and lung cancer xenografts. Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):9623-8. | |
BP-1-102 is an inhibitor of STAT3.1 It binds to STAT3 (Kd = 504 nM) and inhibits STAT3 binding to an IL-6R/gp130 peptide in a fluorescence polarization assay (IC50 = 4.1 μM). BP-1-102 (10-30 μM) decreases viability and proliferation of STAT3-dependent NIH3T3/v-Src, MDA-MB-231, PANC-1, DU145 and A549 cancer cells, but not STAT3-independent NIH3T3, NIH3T3/vRas, TE-71, and A2780S cancer cells. It reduces tumor growth and inhibits expression of the STAT3-dependent genes encoding c-Myc, survivin, Bcl-xL, cyclin D1, and VEGF in MDA-MB-231 and A549 mouse xenograft models when administered at doses of 1 and 3 mg/kg.
1.Zhang, X., Yue, P., Page, B.D., et al.Orally bioavailable small-molecule inhibitor of transcription factor Stat3 regresses human breast and lung cancer xenograftsProc. Natl. Acad. Sci. USA109(24)9623-9628(2012)
| Cas No. | 1334493-07-0 | SDF | |
| Canonical SMILES | O=C(O)C1=CC=C(N(CC2=CC=C(C3CCCCC3)C=C2)C(CN(C)S(=O)(C4=C(F)C(F)=C(F)C(F)=C4F)=O)=O)C=C1O | ||
| 分子式 | C29H27F5N2O6S | 分子量 | 626.59 |
| 溶解度 | DMSO : ≥ 33 mg/mL (52.67 mM) | 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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| 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 | 1.5959 mL | 7.9797 mL | 15.9594 mL |
| 5 mM | 0.3192 mL | 1.5959 mL | 3.1919 mL |
| 10 mM | 0.1596 mL | 0.798 mL | 1.5959 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。
Protective effects of BP-1-102 against intracranial aneurysms-induced impairments in mice
J Drug Target 2021 Nov;29(9):974-982.PMID:33682559DOI:10.1080/1061186X.2021.1895817.
The development of non-invasive pharmacological therapies to prevent the progression and rupture of intracranial aneurysms (IAs) is an important field of research. This study attempts to reveal the role of BP-1-102, an oral bioavailable signal transducer and activator of transcription 3 (STAT3) inhibitor, in IA. We first constructed an IA mouse model by injecting elastase into the cerebrospinal fluid with simultaneous induction of hypertension by deoxycorticosterone acetate (DOCA) implantation. The results showed that the proportion of IA rupture in mice after BP-1-102 administration was significantly reduced, and the survival time was significantly extended. Further research showed that compared with the vehicle group, the proportion of macrophages infiltrated at the aneurysm and the expression of pro-inflammatory cytokines in the BP-1-102 administration group were significantly reduced. The contractile phenotype vascular smooth muscle cell (VSMC) specific markers, SM22α and αSMA, were significantly upregulated in the BP-1-102 group. Furthermore, we found that BP-1-102 inhibited the expression of critical proteins in the nuclear factor kappa-B and Janus kinase 2/STAT3 signalling pathways. Our study shows that BP-1-102 significantly decreases the rupture of IA, reduces the inflammatory responses and modulates the phenotype of VSMCs, suggesting that BP-1-102 could be utilised as a potential intervention drug for IA.
Effects of STAT3 Inhibitor BP-1-102 on The Proliferation, Invasiveness, Apoptosis and Neurosphere Formation of Glioma Cells in Vitro
Cell Biochem Biophys 2022 Dec;80(4):723-735.PMID:35994220DOI:10.1007/s12013-022-01088-y.
Malignant glioma, especially glioblastoma (GBM), has historically been associated with a low survival rate. The hyperactivation of STAT3 played a key role in GBM initiation and resistance to therapy; thus, there is an urgent requirement for novel STAT3 inhibitors. BP-1-102 was recently reported as a biochemical inhibitor of STAT3, but its roles and mechanism in biological behavior of glioma cells were still unclear. In this study, the effects of BP-1-102 on proliferation, apoptosis, invasion and neurosphere formation of glioma cell were investigated. Our results indicated that BP-1-102 inhibited the proliferation of U251 and A172 cells, and their IC50 values were 10.51 and 8.534 μM, respectively. Furthermore, BP-1-102 inhibited the invasion and migration abilities of U251 and A172 cells by decreasing the expression of matrix metallopeptidase 9, and induced glioma cell apoptosis by decreasing the expression of B-cell lymphoma-2. BP-1-102 also inhibited the formation of neurosphere. Mechanically, BP-1-102 reduced the phosphorylation of STAT3 and the p-STAT3's nuclear translocation in glioma cells. Thus, this study herein provided a potential drug for glioma therapy.
Th17-type cytokines, IL-6 and TNF-α synergistically activate STAT3 and NF-kB to promote colorectal cancer cell growth
Oncogene 2015 Jul;34(27):3493-503.PMID:25174402DOI:10.1038/onc.2014.286.
Colorectal cancers (CRCs) often show a dense infiltrate of cytokine-producing immune/inflammatory cells. The exact contribution of each immune cell subset and cytokine in the activation of the intracellular pathways sustaining CRC cell growth is not understood. Herein, we isolate tumor-infiltrating leukocytes (TILs) and lamina propria mononuclear cells (LPMCs) from the tumor area and the macroscopically unaffected, adjacent, colonic mucosa of patients who underwent resection for sporadic CRC and show that the culture supernatants of TILs, but not of LPMCs, potently enhance the growth of human CRC cell lines through the activation of the oncogenic transcription factors signal transducer and activator of transcription 3 (STAT3) and nuclear factor-kappa B (NF-kB). Characterization of immune cell complexity of TILs and LPMCs reveals no differences in the percentages of T cells, natural killer T cells, natural killer (NK) cells, macrophages and B cells. However, T cells from TILs show a functional switch compared with those from LPMCs to produce large amounts of T helper type 17 (Th17)-related cytokines (that is, interleukin-17A (IL-17A), IL-17F, IL-21 and IL-22), tumor necrosis factor-α (TNF-α) and IL-6. Individual neutralization of IL-17A, IL-17F, IL-21, IL-22, TNF-α or IL-6 does not change TIL-derived supernatant-driven STAT3 and NF-kB activation, as well as their proproliferative effect in CRC cells. In contrast, simultaneous neutralization of both IL-17A and TNF-α, which abrogates NF-kB signaling, and IL-22 and IL-6, which abrogates STAT3 signaling, reduces the mitogenic effect of supernatants in CRC cells. IL-17A, IL-21, IL-22, TNF-α and IL-6 are also produced in excess in the early colonic lesions in a mouse model of sporadic CRC, associated with enhanced STAT3/NF-kB activation. Mice therapeutically given BP-1-102, an orally bioavailable compound targeting STAT3/NF-kB activation and cross-talk, exhibit reduced colon tumorigenesis and diminished expression of STAT3/NF-kB-activating cytokines in the neoplastic areas. These data suggest that strategies aimed at the cotargeting of STAT3/NF-kB activation and interaction between them might represent an attractive and novel approach to combat CRC.
BP‑1‑102 exerts antitumor effects on T‑cell acute lymphoblastic leukemia cells by suppressing the JAK2/STAT3/c‑Myc signaling pathway
Exp Ther Med 2023 Mar 15;25(5):191.PMID:37020528DOI:10.3892/etm.2023.11890.
Drug resistance and relapse of T-cell acute lymphoblastic leukemia (T-ALL) remain significant concerns for physicians; hence, the development and screening of effective targeted drugs remain important. Considering that STAT3 is emerging as a potential therapeutic target for T-ALL, T-ALL cell lines (MOLT-4 and CUTLL1) were treated with BP-1-102, a small-molecule inhibitor that blocks STAT3 phosphorylation. Cell Counting Kit-8 assay and colony formation assay results showed that BP-1-102 inhibited T-ALL cell proliferation and colony formation. Flow cytometry and morphological results demonstrated that BP-1-102 dramatically induced apoptosis and caused cell cycle arrest at the G0/G1 phase in T-ALL cell lines. Western blotting results indicated that BP-1-102 suppressed the JAK2/STAT3/c-Myc pathway activity in T-ALL cell lines. In conclusion, BP-1-102 suppressed the JAK2/STAT3/c-Myc signaling pathway in T-ALL cells and exerted various antitumor effects, representing a promising targeted antitumor inhibitor.
Pharmacological inhibition of STAT3 by BP-1-102 inhibits intracranial aneurysm formation and rupture in mice through modulating inflammatory response
Pharmacol Res Perspect 2021 Feb;9(1):e00704.PMID:33474811DOI:10.1002/prp2.704.
As an inhibitor of STAT3, BP-1-102 can regulate the inflammation response caused by vascular smooth muscle cells (VSMCs) by inhibiting the JAK/STAT3/NF-κB pathway, thereby attenuating the symptoms of intracranial aneurysm (IA). IA mouse model was established by stereotactic injection of elastase to evaluate the effect of BP-1-102. The expression levels of smooth muscle markers and matrix metalloproteinases (MMPs) were detected by qRT-PCR, and the levels of inflammatory factors were detected by ELISA and qRT-PCR. The protein levels of the NF-κB signaling pathway factors were examined by Western blot. BP-1-102 reduced blood pressure in aneurysm mice, up-regulated smooth muscle cell markers MHC, SMA, and SM22, and down-regulated the expression of MMP2 and MMP9 in vascular tissues. At the same time, BP-1-102 also down-regulated the expression levels of inflammatory response factors and the NF-κB pathway proteins. In the IA model, BP-1-102 can reduce the expression of inflammatory factors and MMPs bound to NF-κB by inhibiting the activation of the JAK/STAT3/NF-κB pathway proteins, and then restore the vascular wall elastin to reduce blood pressure, thereby treating aneurysm.