NSAH?

SKU: orb1219337

Description

NSAH is a nonnucleoside inhibitor of human ribonucleotide reductase (hRR).with cell-free IC50 of 32 μM and cell-based IC50 of ~250 nM, respectively.A unique nonnucleoside small-molecule hRR inhibitor, naphthyl salicylic acyl hydrazone (NSAH), using virtual screening, binding affinity, inhibition, and cell toxicity assays. NSAH binds to hRRM1 with an apparent dissociation constant of 37 μM, and steady-state kinetics reveal a competitive mode of inhibition. A 2.66- resolution crystal structure of NSAH in complex with hRRM1 demonstrates that NSAH functions by binding at the catalytic site (C-site) where it makes both common and unique contacts with the enzyme compared with NDP substrates. Importantly, the IC for NSAH is within twofold of gemcitabine for growth inhibition of multiple cancer cell lines, while demonstrating little cytotoxicity against normal mobilized peripheral blood progenitor cells. NSAH depresses dGTP and dATP levels in the dNTP pool causing S-phase arrest, providing evidence for RR inhibition in cells.NSAH (0-10 μM, 2, 6, 24, or 72 h) exhibits potent anti-tumor activity in 3 cancer cell lines.

Key Properties

• CAS Number: 1099592-35-4
• MW: 306.3
• Purity: >98% (HPLC)
• Formula: C₁₈H₁₄N₂O₃
• SMILES: O=C(C1=CC=CC=C1O)N/N=C/C2=C3C=CC=CC3=CC=C2O
• Target: DNA/RNA Synthesis
• Solubility: DMSO:62.5 mg/mL (204.03 mM; Need ultrasonic)

Bioactivity

• In Vitro:
  NSAH depresses dGTP and dATP levels in the dNTP pool causing S-phase arrest, providing evidence for RR inhibition in cells. NSAH (0-10 μM, 2, 6, 24, or 72 h) exhibits potent anti-tumor activity in 3 cancer cell lines. NSAH blocks S-phase progression well to the extent and timing of the decreases in dATP and dGTP. Cell Viability Assay Cell line: MDA-231, HCT116 and Panc1 cancer cell lines. Concentration: 0-10 μM. Incubation time: 2, 6, 24, or 72 h. Result: Resulted in IC50 values ranging from 220 to 500 nM.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

2-hydroxy-N'-[(E)-(2-hydroxynaphthalen-1-yl)methylidene]benzohydrazide

Quick Database Links

Gene Symbol

DNA/RNA Synthesis