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Chemical Structure| 64984-31-2 Chemical Structure| 64984-31-2

Structure of Pifithrin-μ
CAS No.: 64984-31-2

Chemical Structure| 64984-31-2

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Pifithrin-μ is an inhibitor of p53 and HSP70 with antitumor and neuroprotective effects.

Synonyms: 2-Phenylethynesulfonamide; PFTμ; PFT-µ

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Product Citations

Product Citations

Wang, Mai ; Phan, Steven ; Hayes, Brandon H. ; Discher, Dennis E. ;

Abstract: Chromosome gains or losses often lead to copy number variations (CNV) and loss of heterozygosity (LOH). Both quantities are low in hematol. "liquid" cancers vs. solid tumors in data of The Cancer Genome Atlas (TCGA) that also shows the fraction of a genome affected by LOH is ∼ one-half of that with CNV. Suspension cultures of p53-null THP-1 leukemia-derived cells conform to these trends, despite novel evidence here of genetic heterogeneity and transiently elevated CNV after perturbation. Single-cell DNAseq indeed reveals at least 8 distinct THP-1 aneuploid clones with further intra-clonal variation, suggesting ongoing genetic evolution. Importantly, acute inhibition of the mitotic spindle assembly checkpoint (SAC) produces CNV levels that are typical of high-CNV solid tumors, with subsequent cell death and down-selection to novel CNV. Pan-cancer analyses show p53 inactivation associates with aneuploidy, but leukemias exhibit a weaker trend even though p53 inactivation correlates with poor survival. Overexpression of p53 in THP-1 does not rescue established aneuploidy or LOH but slightly increases cell death under oxidative or confinement stress, and triggers p21, a key p53 target, but without affecting net growth. Our results suggest that factors other than p53 exert stronger pressures against aneuploidy in liquid cancers, and identifying such CNV suppressors could be useful across liquid and solid tumor types.

Keywords: Aneuploidy ; Hematologic cancer ; Liquid tumor ; Spindle assembly check point (SAC) ; p53

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Product Details of Pifithrin-μ

CAS No. :64984-31-2
Formula : C8H7NO2S
M.W : 181.21
SMILES Code : O=S(C#CC1=CC=CC=C1)(N)=O
Synonyms :
2-Phenylethynesulfonamide; PFTμ; PFT-µ
MDL No. :MFCD00181531
InChI Key :ZZUZYEMRHCMVTB-UHFFFAOYSA-N
Pubchem ID :327653

Safety of Pifithrin-μ

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of Pifithrin-μ

DNA

Isoform Comparison

Biological Activity

Target
  • p53

In Vitro:

Cell Line
Concentration Treated Time Description References
HepG2 cells 5μM/L 1 hour Pretreatment with Pifithrin-μ significantly alleviated GOX-induced mitochondrial dysfunction, including the loss of mitochondrial membrane potential, mitochondrial swelling, and the decrease in ATP levels. PMC4737676
BCBL1 PEL cells 20 µM 12-48 hours PES treatment increased cell death between 12 and 48 hours in both BC3 and BCBL1 cells, indicating time-dependent cytotoxicity. PMC3730433
BC3 PEL cells 10-30 µM 24 hours PES induced a dose-dependent cytotoxic effect in BC3 and BCBL1 PEL cells, leading to lysosome membrane permeabilization, relocation of cathepsin D to the cytosol, Bid cleavage, mitochondrial depolarization, and ultimately programmed cell death. PMC3730433
SNU886 cells 5 μM 24 hours Pifithrin-μ disrupted the interaction between CREB1 and CREBBP, reduced the mRNA levels of CREB1 target genes, and suppressed SESN3 expression, thereby enhancing sorafenib-induced cell death. PMC11762308
HCCLM3 cells 10 μM 24 hours Pifithrin-μ inhibited HSP70 to reduce the transcriptional activity of CREB1 and the expression of SESN3, consequently enhancing sorafenib-induced ferroptosis in mTOR-activated liver cancer cells. PMC11762308
KG-1a (AML) 0.5 to 100 μM 48 hours PFT-μ significantly inhibited cell viability at low micromolar concentrations in all cell lines tested, with IC50 values ranging from 2.5 to 12.7 μM, and was highly active in primary AML blasts with a median IC50 of 8.9 μM. PFT-μ induced apoptosis and cell cycle arrest in a dose-dependent manner in AML and ALL. PMC3255249
NALM-6 (B-precursor ALL) 0.5 to 100 μM 48 hours PFT-μ significantly inhibited the viability of NALM-6 cells, with an IC50 value of 2.5 μM. PFT-μ led to an increase in the active form of caspase-3 and reduced intracellular concentrations of AKT and ERK1/2. PMC3255249
TOM-1 (B-precursor ALL; BCR-ABL positive) 0.5 to 100 μM 48 hours PFT-μ significantly inhibited the viability of TOM-1 cells, with an IC50 value of 6.1 μM. PFT-μ enhanced the cytotoxicity of cytarabine, 17-AAG, SAHA, and sorafenib in TOM-1 cells. PMC3255249
HONE1/Akata cells 40 µM 48 hours PES significantly decreased the expression of EBNA1, independent of effects on EBNA1 transcription or proteasomal degradation. PMC6026193
HK1/Akata cells 40 µM 48 hours PES significantly decreased the expression of EBNA1, independent of effects on EBNA1 transcription or proteasomal degradation. PMC6026193
B95-8 cells 10 µM 48 hours PES significantly decreased the expression of EBNA1, independent of effects on EBNA1 transcription or proteasomal degradation. PMC6026193

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
WT and Traf6−/− mice Traf6−/− mice Intraperitoneal injection 10 mg/kg Every other day for one week Pifithrin-μ reversed the spontaneous apoptosis in Traf6?/? thymus, while pifithrin-α did not have this effect PMC5541903
C57BL/6J mice Cisplatin-induced cognitive impairment model Intraperitoneal injection 8 mg/kg Once daily for two 5-day cycles PFT-μ completely prevented cisplatin-induced cognitive impairment and associated structural changes in the brain, including loss of white matter integrity and neurogenic areas. PMC5290207
BALB/c Nude mice Subcutaneous xenograft model Intraperitoneal injection (Pifithrin-μ), Oral administration (sorafenib) 10 mg/kg Every other day, until the end of the experiment Combined treatment of Pifithrin-μ and sorafenib significantly inhibited tumor growth in mTOR-activated liver cancer cells, reduced tumor volume and weight, and had no significant impact on the body weight of mice. PMC11762308
BALB/c Nude mice HONE1/Akata cell-induced tumor model Intraperitoneal injection 8 mg/kg Once daily for 5 consecutive days PES significantly inhibited the growth of tumors induced by HONE1/Akata cells and reduced the expression of EBNA1 in tumor tissues. PMC6026193

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

5.52mL

1.10mL

0.55mL

27.59mL

5.52mL

2.76mL

55.18mL

11.04mL

5.52mL

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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