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

• ChemBase ID: 73180
• Molecular Formular: C11H13N5O4
• Molecular Mass: 279.25202
• Monoisotopic Mass: 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

NAMES AND DATABASE IDS

Names

• IUPAC name: 7-(4-methylpiperazin-1-yl)-4-nitro-2,1,3-benzoxadiazol-1-ium-1-olate
• IUPAC Traditional name: 7-(4-methylpiperazin-1-yl)-4-nitro-2,1,3-benzoxadiazol-1-ium-1-olate
• Synonyms: XI-006; NSC-207895

Database IDs

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

CALCULATED PROPERTIES

• H Acceptors: 7
• H Donor: 0
• LogD (pH = 5.5): -0.9588745
• LogD (pH = 7.4): 0.71045935
• Log P: 1.1007
• Molar Refractivity: 93.2386 cm^3
• Polarizability: 26.576202 Å^3
• Polar Surface Area: 103.79 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: true

PROPERTIES

Safety Information

• Storage Condition: -20°C

Pharmacology Properties

• Target: p53

Product Information

• Salt Data: Free Base

DETAILS

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.

REFERENCES

• 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.