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Chemical Structure| 803647-40-7 Chemical Structure| 803647-40-7

Structure of NSC59984
CAS No.: 803647-40-7

Chemical Structure| 803647-40-7

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NSC 59984 is a reactivator of p53 which targets various mutant p53 to restore wild-type p53 pathway via the activation of p73 in cancer cells. It could induce p53 mutant protein degradation via MDM2-mediated ubiquitination.

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Product Details of NSC59984

CAS No. :803647-40-7
Formula : C12H15N3O4
M.W : 265.27
SMILES Code : O=C(N1CCN(C)CC1)/C=C/C2=CC=C([N+]([O-])=O)O2
MDL No. :MFCD29905462
InChI Key :QKTRIGNWBRHBFV-DUXPYHPUSA-N
Pubchem ID :5356520

Safety of NSC59984

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

Description
NSC59984 targets mutant p53 for degradation through MDM2 and the ubiquitin-proteasome pathway[1].

In Vitro:

Cell Line
Concentration Treated Time Description References
Detroit 562 cells 100 μM NSC59984 had a lesser effect on repressing Detroit 562 cell growth. PMC8946684
DLD-1 25 μmol/L 16 hours NSC59984 induces ERK2-dependent cell death and inhibits colony formation. PMC8983457
HT29 25 μmol/L 16 hours NSC59984 induces mutant p53 degradation via ROS-ERK2-MDM2 axis and restores p53 pathway signaling. PMC8983457
SW480 25 μmol/L 16 hours NSC59984 induces sustained phosphorylation of ERK2 via ROS, promotes MDM2 phosphorylation at serine-166, enhances phosphorylated-MDM2 binding to mutant p53, leading to mutant p53 ubiquitination and degradation. PMC8983457
OECM-1 cells 100 μM NSC59984 could repress OECM-1 cell growth and upregulate p73 downstream genes NEU4, JAG2, LIG1, and G6PD. PMC8946684
Barrett's esophagus cells CP-A-WT 12 µM 72 hours NSC59984 treatment had minimal effects on proliferation and apoptosis in CP-A-WT cells. PMC9874945
Esophageal adenocarcinoma cells EsC3-R175H 12 µM 72 hours NSC59984 treatment led to reduced proliferation and increased apoptosis, but the effects were weaker compared to ESO26-R248W cells. PMC9874945
Esophageal adenocarcinoma cells ESO26-R248W 12 µM 72 hours NSC59984 treatment significantly reduced cellular proliferation and increased apoptosis as measured by Annexin V, showing a 3-fold higher response compared to EsC3-R175H cells. PMC9874945
THP-1 cells 12 µM 48 h Combination treatment of THP-1 cells with venetoclax and NSC59984 significantly increased the apoptotic fraction and downregulated the expression levels of DRP1 and p-DRP1 S616. PMC9913445
MOE cells 25 μM/L 8 hours NSC59984 degraded mutant p53 protein and rescued CDH6 repression in MOE cells with p53R273H. PMC5342521

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Nude mice DLD-1 xenograft model Intraperitoneal injection 45mg/kg Every 5 days for 15 days Inhibits tumor growth, reduces tumor weight by 34% PMC4573895
Nude mice HT29 xenograft tumor model Intraperitoneal injection 75 mg/kg Every 3 days for 2 weeks NSC59984 in combination with BSO significantly suppressed tumor growth, increased the index of cleaved-caspase 3 and reduced Ki67 index. PMC8983457

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

3.77mL

0.75mL

0.38mL

18.85mL

3.77mL

1.88mL

37.70mL

7.54mL

3.77mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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