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HomeProduct name listNSC59984

NSC59984

  • CAS NO.:803647-40-7
  • Empirical Formula: C12H15N3O4
  • Molecular Weight: 265.27
  • MDL number: MFCD29905462
  • Update Date: 2024-11-19 20:33:22
NSC59984 Structural

What is NSC59984?

Description

NSC59984 (803647-40-7) is a p53 activator.? Restores wild-type p53 signaling and depletes mutant p53 gain of function. Induces mutant p53 protein degradation via MDM2 and ubiquitin-proteasome pathway. Induces p73-dependent cell death in cancer cells without toxicity toward normal cells.1?Inhibition of p53-MDM2 interaction remains a viable strategy for cancer therapeutic development.2,3

in vitro

in sw480 and dld-1 cells, nsc59984 treatment for 3 hours dose-dependently increased the mrna levels of p21, noxa and puma. nsc59984 was also found to increase p53-responsive reporter activity in both sw480 in a dose-dependent manner. the ec50 values of nsc59984 against a panel of cancer cell lines were different, varying from 8.38 to 110.49 μm. after incubation with 12 μm nsc59984 for 8 hours, the level ofγh2ax, a marker of genotoxicity due to dna double-strand breaks, increased in hct116 cells. nsc59984 induced cell death in apanel of cancer cells but displayed little or no cytotoxicity towards normal cells.noxa mrna slightly increased in response to 25 μm of nsc59984 in hct116 and 12 μm of nsc59984 in p53-null hct116 cells [1].

in vivo

in nude mice bearing colon-tumor xenografts, nsc59984 (i.p. injection, 45mg/kg) did not cause an obvious change in mouse body weights and no overt toxic effects. nsc59984 treatment significantly repressed the dld-1 xenograft tumor growth. tumor weight measured at day 15 reduced by 34% in dld-1 xenograft tumors. in p73 knock-down dld-1 xenograft tumors, nsc59984 didn’t suppress tumor growth. in p73 knock-down dld-1 xenograft tumors, nsc59984 treatment reduced tumor weight by 18% [1].

References

1) Zhang?et al.?(2015),?Small-Molecule NSC59984 Restores p53 Pathway Signaling and Antitumor effects against Colorectal Cancer via p73 Activation and Degradation of Mutant p53; Cancer Res.,?75?3842 2) Ferraiuolo?et al.?(2016),?Oncogenic Intra-p53 Family Member Interactions in Human Cancers; Front. Oncol.,?6?77 3) Hong?et al.?(2014),?Targeting tumor suppressor p53 for cancer therapy: strategies, challenges and opportunities; Curr. Drug Targets,?15?80

Properties of NSC59984

Boiling point: 451.8±45.0 °C(Predicted)
Density  1.304±0.06 g/cm3(Predicted)
storage temp.  2-8°C
solubility  Soluble in DMSO (up to 20 mg/ml)
form  solid
pka 6.72±0.10(Predicted)
color  Off-white
Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month.

Safety information for NSC59984

Signal word Warning
Pictogram(s)
ghs
Exclamation Mark
Irritant
GHS07
GHS Hazard Statements H315:Skin corrosion/irritation
H319:Serious eye damage/eye irritation
H335:Specific target organ toxicity, single exposure;Respiratory tract irritation
Precautionary Statement Codes P261:Avoid breathing dust/fume/gas/mist/vapours/spray.
P305+P351+P338:IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

Computed Descriptors for NSC59984

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