• CAT Number: I004928
  • CAS Number: 803647-40-7
  • Molecular Formula: C12H15N3O4
  • Molecular Weight: 265.3
  • Purity: ≥95%
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NSC59984 is a compound that promotes the degradation of mutant p53 protein through the MDM2 and ubiquitin-proteasome pathways. It achieves this by targeting specifically the GOF-mutant form of p53. Additionally, NSC59984 activates p73, a protein that is similar to p53, but is not mutated in cancer cells. This activation restores the p53 signaling pathway, which is often disrupted in cancer cells with mutant p53. Therefore, NSC59984 shows potential as a therapeutic agent for treating cancers with mutant p53.

Catalog Number I004928
CAS Number 803647-40-7
Molecular Formula


Purity 95%
Target p53
Solubility DMSO: ≥ 38 mg/mL
Storage 2-8°C
IC50 8.38 μM (EC50, for p53-null HCT116 cells)
IUPAC Name (E)-1-(4-methylpiperazin-1-yl)-3-(5-nitrofuran-2-yl)prop-2-en-1-one
InChI InChI=1S/C12H15N3O4/c1-13-6-8-14(9-7-13)11(16)4-2-10-3-5-12(19-10)15(17)18/h2-5H,6-9H2,1H3/b4-2+

1:Cancer Res. 2015 Sep 15;75(18):3842-52. doi: 10.1158/0008-5472.CAN-13-1079. Epub 2015 Aug 20. Small-Molecule NSC59984 Restores p53 Pathway Signaling and Antitumor Effects against Colorectal Cancer via p73 Activation and Degradation of Mutant p53.Zhang S,Zhou L,Hong B,van den Heuvel AP,Prabhu VV,Warfel NA,Kline CL,Dicker DT,Kopelovich L,El-Deiry WS, PMID: 26294215 PMCID: PMC4573895 DOI: 10.1158/0008-5472.CAN-13-1079 </br><span>Abstract:</span> The tumor-suppressor p53 prevents cancer development via initiating cell-cycle arrest, cell death, repair, or antiangiogenesis processes. Over 50% of human cancers harbor cancer-causing mutant p53. p53 mutations not only abrogate its tumor-suppressor function, but also endow mutant p53 with a gain of function (GOF), creating a proto-oncogene that contributes to tumorigenesis, tumor progression, and chemo- or radiotherapy resistance. Thus, targeting mutant p53 to restore a wild-type p53 signaling pathway provides an attractive strategy for cancer therapy. We demonstrate that small-molecule NSC59984 not only restores wild-type p53 signaling, but also depletes mutant p53 GOF. NSC59984 induces mutant p53 protein degradation via MDM2 and the ubiquitin-proteasome pathway. NSC59984 restores wild-type p53 signaling via p73 activation, specifically in mutant p53-expressing colorectal cancer cells. At therapeutic doses, NSC59984 induces p73-dependent cell death in cancer cells with minimal genotoxicity and without evident toxicity toward normal cells. NSC59984 synergizes with CPT11 to induce cell death in mutant p53-expressing colorectal cancer cells and inhibits mutant p53-associated colon tumor xenograft growth in a p73-dependent manner in vivo. We hypothesize that specific targeting of mutant p53 may be essential for anticancer strategies that involve the stimulation of p73 in order to efficiently restore tumor suppression. Taken together, our data identify NSC59984 as a promising lead compound for anticancer therapy that acts by targeting GOF-mutant p53 and stimulates p73 to restore the p53 pathway signaling.©2015 American Association for Cancer Research.

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