7-(4-methylpiperazin-1-yl)-4-nitro-2,1,3-benzoxadiazol-1-ium-1-olate

• ChemBase编号: 73180
• 分子式: C11H13N5O4
• 平均质量: 279.25202
• 单一同位素质量: 279.09675392
• SMILES: C1CN(CCN1c1c2c(c(cc1)[N+](=O)[O-])no[n+]2[O-])C
• Canonical SMILES: CN1CCN(CC1)c1ccc(c2c1[n+]([O-])on2)[N+](=O)[O-]
• InChI: InChI=1S/C11H13N5O4/c1-13-4-6-14(7-5-13)9-3-2-8(15(17)18)10-11(9)16(19)20-12-10/h2-3H,4-7H2,1H3
• InChIKey: MWFZDJLPWDCQIL-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: 7-(4-methylpiperazin-1-yl)-4-nitro-2,1,3-benzoxadiazol-1-ium-1-olate
• IUPAC传统名: 7-(4-methylpiperazin-1-yl)-4-nitro-2,1,3-benzoxadiazol-1-ium-1-olate
• 别名: XI-006; NSC-207895

登记号

• CAS号: 58131-57-0
• PubChem SID: 162038100
• PubChem CID: 42640

理论计算性质

• 质子受体: 7
• 质子供体: 0
• LogD (pH = 5.5): -0.9588745
• LogD (pH = 7.4): 0.71045935
• Log P: 1.1007
• 摩尔折射率: 93.2386 cm^3
• 极化性: 26.576202 Å^3
• 极化表面积: 103.79 Å^2
• 可自由旋转的化学键: 2
• 里宾斯基五规则: true

分子性质

安全信息

• 保存条件: -20°C

药理学性质

• 作用靶点: p53

产品相关信息

• 成盐信息: Free Base

详细说明

Selleck Chemicals - S2678

Biological Activity

• Description: NSC-207895 is novel inhibitor of MDMX and activates p53.
• Targets:

  MDMX

• In Vitro: NSC-207895 decreases both the MDMX mRNA and protein in MCF-7 cells. NSC-207895 induces expression of p53 as well as well-characterized p53-target gene, p21 and MDM2, in a dose-dependent manner in MCF-7 cells. NSC-207895 extends the half-life of p53 from 20 to 30 minutes to more than 3 hours as revealed by cycloheximide chase assays in MCF-7 cells. NSC-207895 also activates p53 and induces p21 and MDM2 expression in LNCaP prostate and A549 lung cancer cells. NSC-207895 increases the mRNA levels of proapoptotic genes including PUMA, BAX, and PIG3 in a dose-dependent manner in MCF-7 cells. NSC-207895 results in a significant increase in the numbers of sub-G0/G1 cells as well as G2 arrest. NSC-207895 also results in more than 40% of cells dying via apoptosis and decreases cell viability in A549 and LNCaP cells. ^[1] NSC-207895 inhibits biosynthesis of nucleic acids and proteins in L1210 cells. ^[2] NSC-207895 interacts with DNA repair to activate the DNA damage repair pathway in three species (S. cerevisiae, S. pombe and H. sapiens). ^[3] NSC-207895 acts as cytotoxic agent in the G/R-luc astrocytoma cell line with GI50 of 117 nM. ^[4]

Combination Therapy

• Description:

  NSC-207895 (2 μM) decreased cell survival in combination with low concentrations of Nutltin-3 in an additive manner. While NSC-207895 does not affect significantly Nutlin-3–induced decrease of cell viability. ^[1]

Protocol

• Protocol: Cell Assay ^[1]
• Cell Lines: MCF-7 cell
• Concentrations: 1-10 μM
• Incubation Time: 2 days
• Methods:

  MCF-7 cells treated with dimethyl sulfoxide (DMSO), nutlin-3a, or NSC-207895 are permeabilized with cold 70% ethanol overnight, and stained with a solution containing 50 μg/mL propidium iodide and 20 μg/mL RNase A at 37°C for 20 minutes. The cells are then subjected to flow cytometry analysis. The FlowJo software is used to calculate percentages of cells in each cell cycle phase. For terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling (TUNEL) staining, MCF-7 cells treated with the NSC-207895 for 2 days are fixed with 4% paraformadelhyde for 1 hour, and then subjected to dUTP labeling using In Situ Cell Death Detection Kit TMR Red according to the manufacturer's protocol. For quantitation, at least 300 cells are randomly chosen and the numbers of TUNEL-positive cells are counted.

References

• References: [1] Wang H, et al. Mol Cancer Ther, 2011, 10(1), 69-79.
• References: [2] Kessel D, et al. Cancer Res, 1975, 35(12), 3735-3740.
• References: [3] Kapitzky L, et al. Mol Syst Biol, 2010, 6, 451.
• References: [4] Hawes JJ, et al. J Biomol Screen, 2008, 13(8), 795-803.

参考文献

• Wang H, et al. Mol Cancer Ther, 2011, 10(1), 69-79.
• Kessel D, et al. Cancer Res, 1975, 35(12), 3735-3740.
• Kapitzky L, et al. Mol Syst Biol, 2010, 6, 451.
• Hawes JJ, et al. J Biomol Screen, 2008, 13(8), 795-803.