BN82002
目录号 : GC33345
BN82002是CDC25磷酸酶的合成抑制剂，其对重组CDC25磷酸酶的IC50值为2.4-6.3μM。
Cas No.:396073-89-5
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
BN82002 is a synthetic inhibitor of CDC25 phophatases, with IC50s of 2.4-6.3 μM for recombinant CDC25 phosphatases.
The effect of BN82002 on cell proliferation is evaluated in vitro on several human tumor cell lines. Menadione, which has been reported to inhibit cell proliferation, is used as a control. All of the examined cell lines are sensitive to BN82002 and Menadione in a concentration-dependent manner in the low micromolar range. The most sensitive is the pancreatic cancer cell line MIA PaCa-2 with an IC50 of 7.2 μM, and the less sensitive cell line is the colon cancer HT-29 with an IC50 of 32.6 μM. The range of activity is very similar to the one observed with menadione (5-15 μM). It is also showed that 50 μM BN82002 is a concentration that fully inhibits cell proliferation, the cell cycle distribution is only modestly affected with a slight decrease in S phase and an increase in cells containing both a G1 and a G2 DNA content, suggesting that the cells treated with BN82002 are arrested at various stages of the cell cycle[1].
[1]. Brezak MC, et al. A novel synthetic inhibitor of CDC25 phosphatases: BN82002. Cancer Res. 2004 May 1;64(9):3320-5.
| Cas No. | 396073-89-5 | SDF | |
| Canonical SMILES | OC1=C(CN(C)CCC2=CC=C([N+]([O-])=O)C=C2)C=C(N(C)C)C=C1OC | ||
| 分子式 | C19H25N3O4 | 分子量 | 359.42 |
| 溶解度 | DMSO : ≥ 150 mg/mL (417.34 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 | 2.7823 mL | 13.9113 mL | 27.8226 mL |
| 5 mM | 0.5565 mL | 2.7823 mL | 5.5645 mL |
| 10 mM | 0.2782 mL | 1.3911 mL | 2.7823 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。
BN82002 alleviated tissue damage of septic mice by reducing inflammatory response through inhibiting AKT2/NF-κB signaling pathway
Biomed Pharmacother 2022 Apr;148:112740.PMID:35202908DOI:10.1016/j.biopha.2022.112740.
BN82002 is well-known as an inhibitor of the CDC25 phosphatase. However, it was recently reported that BN82002 also selectively suppressed AKT2 and reduced inflammatory responses in lipopolysaccharide (LPS)-stimulated macrophage-like RAW264.7 cells. Therefore, in this study, we evaluated the alleviating efficacy of BN82002 in sepsis in vivo. BN82002 (50 μM) suppressed the mRNA levels of cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in LPS-treated peritoneal macrophages without cytotoxicity. The septic in vivo mouse model was established on the basis of the endotoxin model using poly(I:C) (10 mg/kg) and LPS (54 mg/kg). In histological analysis, peritoneal injection of BN82002 (20 mg/kg) significantly reduced lung, kidney, and liver damage. Lung edema and serum alanine transaminase (ALT), aspartate transaminase (AST), TNF-α, IL-1β, and nitric oxide (NO) levels also were decreased by BN82002 (20 mg/kg). In addition, BN82002 (20 mg/kg) suppressed the mRNA levels of TNF-α in lung and liver tissues. Gene expression levels of IL-1β and IL-6 were decreased in lung, kidney, and liver in the BN82002 (20 mg/kg) group. Furthermore, p-AKT2 and p-IκBα levels were reduced by BN82002 (20 mg/kg). Finally, all septic mice died 7 days after poly(I:C)/LPS-injection, whereas 4 mice in the BN82002 (20 mg/kg) group, survived strongly suggesting that BN82002 reduces sepsis mortality. In conclusion, we verified that pre-treatment with BN82002 protects against tissue damage and increases survival by inhibiting AKT2-NF-κB signaling in septic mice. These results suggest that BN82002 could be utilized in the treatment of sepsis.
Anti-inflammatory functions of the CDC25 phosphatase inhibitor BN82002 via targeting AKT2
Biochem Pharmacol 2019 Jun;164:216-227.PMID:30980807DOI:10.1016/j.bcp.2019.04.007.
This study presents BN82002 as an anti-inflammatory drug candidate. It was found that BN82002 inhibited the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in RAW 264.7 cells and peritoneal macrophages that were activated by toll-like receptor (TLR) 4 ligand, lipopolysaccharide (LPS). BN82002 dose-dependently down-regulated mRNA levels of nitric oxide synthase, tumor necrosis factor-α, and cyclooxygenase-2. The nuclear translocation of nuclear factor (NF)-κB (p65 and p50) was also blocked by BN82002 in RAW265.7 cells stimulated by LPS. According to reporter gene assay performed with NF-κB construct, BN82002 clearly reduced increased level of luciferase activity mediated by transcription factor NF-κB in LPS-treated RAW264.7 cells and in MyD88- and AKT2-overexpressing HEK293 cells. However, BN82002 did not inhibit NF-κB activity in AKT1- or IKKβ-overexpressing HEK293 cells. NF-κB upstream signaling events specifically targeted AKT2 but had no effect on AKT1. The specific target of BN82002 was Tyr-178 in AKT2. BN82002 bound to Tyr-178 and interrupted the kinase activity of AKT2, according to a cellular thermal shift assay analysis of the interaction of BN82002 with AKT2 and an AKT2 mutant (Tyr-178 mutated to Ala; AKT2 Y178A). These results suggest that BN82002 could reduce inflammatory pathway by controlling NF-κB pathway and specifically targeting AKT2.
A novel synthetic inhibitor of CDC25 phosphatases: BN82002
Cancer Res 2004 May 1;64(9):3320-5.PMID:15126376DOI:10.1158/0008-5472.can-03-3984.
CDC25 dual-specificity phosphatases are essential regulators that dephosphorylate and activate cyclin-dependent kinase/cyclin complexes at key transitions of the cell cycle. CDC25 activity is currently considered to be an interesting target for the development of new antiproliferative agents. Here we report the identification of a new CDC25 inhibitor and the characterization of its effects at the molecular and cellular levels, and in animal models. BN82002 inhibits the phosphatase activity of recombinant human CDC25A, B, and C in vitro. It impairs the proliferation of tumoral cell lines and increases cyclin-dependent kinase 1 inhibitory tyrosine phosphorylation. In synchronized HeLa cells, BN82002 delays cell cycle progression at G1-S, in S phase and at the G2-M transition. In contrast, BN82002 arrests U2OS cell cycle mostly in the G1 phase. Selectivity of this inhibitor is demonstrated: (a) by the reversion of the mitotic-inducing effect observed in HeLa cells upon CDC25B overexpression; and (b) by the partial reversion of cell cycle arrest in U2OS expressing CDC25. We also show that BN82002 reduces growth rate of human tumor xenografts in athymic nude mice. BN82002 is a original CDC25 inhibitor that is active both in cell and animal models. This greatly reinforces the interest in CDC25 as an anticancer target.
CDC25 Inhibition in Acute Myeloid Leukemia-A Study of Patient Heterogeneity and the Effects of Different Inhibitors
Molecules 2017 Mar 11;22(3):446.PMID:28287460DOI:10.3390/molecules22030446.
Cell division cycle 25 (CDC25) protein phosphatases regulate cell cycle progression through the activation of cyclin-dependent kinases (CDKs), but they are also involved in chromatin modulation and transcriptional regulation. CDC25 inhibition is regarded as a possible therapeutic strategy for the treatment of human malignancies, including acute myeloid leukemia (AML). We investigated the in vitro effects of CDC25 inhibitors on primary human AML cells derived from 79 unselected patients in suspension cultures. Both the previously well-characterized CDC25 inhibitor NSC95397, as well as five other inhibitors (BN82002 and the novel small molecular compounds ALX1, ALX2, ALX3, and ALX4), only exhibited antiproliferative effects for a subset of patients when tested alone. These antiproliferative effects showed associations with differences in genetic abnormalities and/or AML cell differentiation. However, the responders to CDC25 inhibition could be identified by analysis of global gene expression profiles. The differentially expressed genes were associated with the cytoskeleton, microtubules, and cell signaling. The constitutive release of 28 soluble mediators showed a wide variation among patients and this variation was maintained in the presence of CDC25 inhibition. Finally, NSC95397 had no or only minimal effects on AML cell viability. In conclusion, CDC25 inhibition has antiproliferative effects on primary human AML cells for a subset of patients, and these patients can be identified by gene expression profiling.
Synthesis of small molecule CDC25 phosphatases inhibitors
Bioorg Med Chem Lett 2004 Dec 6;14(23):5809-12.PMID:15501045DOI:10.1016/j.bmcl.2004.09.041.
A targeted library of small molecules has been prepared to optimize the biological activity of BN82002, our initial lead compound, recently described as an original inhibitor of CDC25 phosphatases. Some of these compounds inhibit CDC25 in the micromolar range and therefore reinforce the interest of CDC25 as an anticancer target.