Pifithrin-µ

Names

[ Name ]:
Pifithrin-µ

[Synonym ]:
2-Phenylethynesulfonamide
Pifithrin-mu
2-Phenylacetylenesulfonamide
Phenyl-ethynesulfonic acid amide
Ethynesulfonamide, 2-phenyl-
Phenylethynsulfonic acid amide
PFTmu
Pifithrin-μ

Biological Activity

[Description]:

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

[Related Catalog]:

Signaling Pathways >> Apoptosis >> MDM-2/p53

Research Areas >> Cancer

Research Areas >> Neurological Disease

[Target]

HSP70

MDM-2/p53

[In Vitro]

Pifithrin-μ (10 μM) is a p53 inhibitor, which inhibits p53 binding to mitochondria by reducing its affinity to antiapoptotic proteins Bcl-xL and Bcl-2 but has no effect on p53-dependent transactivation, activity of caspases 2, 8, 9 and 10 in a cell-free system, or NF-κB-dependent transcription[1]. Pifithrin-μ (PES) time- and dose-dependently reduces viability in A549 cells, with IC50s of 44.9 and 25.7 µM at 24 h and 48 h. Pifithrin-μ (20 μM) suppresses the cell migration, induces cell cycle arrest and cell apoptosis in A549 and H460 cells. Pifithrin-μ (10 or 20 µM) inhibits activities of AKT, ERK, and Hsp70 in A549 and H460 cells. Pifithrin-μ (20 µM) sensitizes A549 and H460 cell lines to TRAIL-induced cell proliferation inhibition and apoptosis[2].

[In Vivo]

Pifithrin-μ (40 mg/kg, i.p.) shows no protective effect against doses of radiation that cause gastrointestinal syndrome in mice[1]. Pifithrin-μ (PES, 10 mg/kg) shows antitumor effect in mice bearing A549 cells[2]. Pifithrin-μ exhibits neuroprotective effect with the P53-inhibitor pifithrin-μ after cardiac arrest in a rodent model[3].

[Cell Assay]

The cell viability is determined by the Cell Counting Kit-8 assay. Briefly, A549 and H460 cells are incubated in 96-well plates at a density of 5 × 103 per 100 µL of culture medium overnight. After treated with indicated concentration of Pifithrin-μ for 24 and 48 h, 10 µL of tetrazolium substrate are added to each well of the plate. After incubation at 37°C for 1 h, the absorbance is recorded at a wavelength of 450 nm using a microplate reader. Each experiment is determined in triplicate and repeated at least three times[2].

[Animal admin]

Mice[2] A549 cells (1 × 107) are suspended in Matrigel and inoculated subcutaneously into the mice. Twelve mice bearing evident tumors are arbitrarily assigned to PBS control group and Pifithrin-μ treatment groups (six mice per group). When tumors reach a size of ∼5×5 mm2, mice are treated with either a single of intraperitoneal injection of Pifithrin-μ (20 mg/kg) or PBS every two days. After 3-week treatment, mice are euthanized with carbon dioxide. Tumor burdens are evaluated by measuring body weight, tumor weight, and tumor volume. Tumor volume is determined as 0.5 × length × width2. Tumor samples are collected and fixed in 10% neutral buffered formalin. Hematoxylin and eosin staining and immunohistochemistry for histological analysis of tumor samples are measured[2].

[References]

[1]. Strom E, et al. Small-molecule inhibitor of p53 binding to mitochondria protects mice from gamma radiation. Nat Chem Biol. 2006 Sep;2(9):474-9. Epub 2006 Jul 23.

[2]. Zhou Y, et al. Pifithrin-μ is efficacious against non-small cell lung cancer via inhibition of heat shock protein 70. Oncol Rep. 2017 Jan;37(1):313-322.

[3]. Glas M, et al. Neuroprotection with the P53-Inhibitor Pifithrin-μ after Cardiac Arrest in a Rodent Model. Shock. 2018 Feb;49(2):229-234.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
351.7±25.0 °C at 760 mmHg

[ Melting Point ]:
135.0 to 139.0 °C

[ Molecular Formula ]:
C₈H₇NO₂S

[ Molecular Weight ]:
181.212

[ Flash Point ]:
166.5±23.2 °C

[ Exact Mass ]:
181.019745

[ PSA ]:
68.54000

[ LogP ]:
2.00

[ Vapour Pressure ]:
0.0±0.8 mmHg at 25°C

[ Index of Refraction ]:
1.634

[ Storage condition ]:
2-8°C

[ Water Solubility ]:
DMSO: soluble >10mg/mL, clear

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302-H315-H319-H335

[ Precautionary Statements ]:
P261-P305 + P351 + P338

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves

[ Hazard Codes ]:
Xn: Harmful;

[ Risk Phrases ]:
22-36/37/38

[ Safety Phrases ]:
26

[ RIDADR ]:
NONH for all modes of transport

[ HS Code ]:
2935009090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2935009090

[ Summary ]:
2935009090 other sulphonamides VAT:17.0% Tax rebate rate:9.0% Supervision conditions:none MFN tariff:6.5% General tariff:35.0%

Articles

Cell death induced by 2-phenylethynesulfonamide uncovers a pro-survival function of BAX.

Cancer Lett. 354(1) , 115-21, (2014)

PES (2-phenylethynesulfonamide) was initially identified as an inhibitor of p53 translocation to mitochondria and named Pifithrin-µ. Further studies showed that PES selectively killed tumour cells and...

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Immune responses contribute to the success of radiotherapy of solid tumors; however, the mechanism of triggering CD8(+) T-cell responses is poorly understood. Antigen cross-presentation from tumor cel...