| Identification | Back Directory | [Name]
PHENYLETHYNSULFONIC ACID AMIDE | [CAS]
64984-31-2 | [Synonyms]
PFT
Pftmu
CS-1119
NSC 303580
Pifithrin--
Pifithrin-u
PIFITHRIN-MU
Pifithrin-μ
Pifithrin-mu>
Pifithrin-μ USP/EP/BP
PHENYLETHYNESULFONAMIDE
2-Phenylethynesulfonamide
2-Phenyl-ethynesulfoanide
Phenylacetylenylsulfonamide
EthynesulfonaMide, 2-phenyl-
2-PHENYLACETYLENESULFONAMIDE
PHENYLETHYNSULFONIC ACID AMIDE
Phenyl-ethynesulfonic Acid Amide
2-Phenylethynesulfonamide, PFTμ
2-(3-chlorophenyl)-ethynesulfonamide
Pifithrin-μ - CAS 64984-31-2 - Calbiochem
Phenylethynsulfonic Acid Amide
P0122_Sigma | [Molecular Formula]
C8H7NO2S | [MDL Number]
MFCD00181531 | [MOL File]
64984-31-2.mol | [Molecular Weight]
181.212 |
| Chemical Properties | Back Directory | [Melting point ]
135.0 to 139.0 °C | [Boiling point ]
351.7±25.0 °C(Predicted) | [density ]
1.39±0.1 g/cm3(Predicted) | [storage temp. ]
2-8°C | [solubility ]
DMSO: soluble >10mg/mL, clear | [form ]
solid | [pka]
7.96±0.60(Predicted) | [color ]
White or off-white | [Stability:]
Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months. | [InChIKey]
ZZUZYEMRHCMVTB-UHFFFAOYSA-N |
| Hazard Information | Back Directory | [Description]
In addition to its transactivational functions, p53 mediates apoptosis by binding with the anti-apoptotic proteins Bcl-xL and Bcl-2 at the mitochondrial surface. Pifithrin-μ (PFT-μ) is an inhibitor of p53-mediated apoptosis, preventing p53 binding to Bcl-xL and Bcl-2 at the mitochondria without affecting p53 transactivational activities In vitro, PFT-μ binds both p53 (Kd = 0.82 mM) and Bcl-xL (Kd = 0.80 mM). PFT-μ reduces p53-mediated apoptosis induced by γ-radiation in mouse thymocytes in vitro and protects mice from doses of radiation that cause lethal hematopoietic syndrome. At 25 μM, PFT-μ reduces apoptosis triggered by nutlin-3, which inhibits MDM2/p53 binding and potentiates p53-mediated growth arrest and apoptosis. PFT-μ also interacts selectively with heat shock protein 70 (Hsp70), leading to disruption of the association between Hsp70 and many of its co-chaperones and substrate proteins. | [Uses]
A small molecule inhibitor of p53 binding to mitochondria protects mice from gamma radiation | [Uses]
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. Pifithrin-μ has also been shown to inhibit HSP70 leading to tumor cell death associated with protein aggregation, impaired autophagy and inhibition of lysosomal function. | [Definition]
ChEBI: 2-phenylethynesulfonamide is a member of benzenes. | [General Description]
A cell-permeable sulfonamide that blocks p53 interaction with Bcl-xL and Bcl-2 proteins and selectively inhibits p53 translocation to mitochondria without affecting the transactivation function of p53. Effectively protects against γ radiation-induced cell death in vitro and animal lethality in vivo. Because Pifithrin-μ targets only the mitochondrial branch of the p53 pathway without affecting the important transcriptional functions of p53, it is superior to Pifithrin-α (Cat. No. 506132) in in vivo studies. Shown to selectively interact with inducible HSP70 and disrupt its functions. | [Biological Activity]
Inhibits p53 binding to mitochondria by reducing its affinity for antiapoptotic proteins Bcl-2 and Bcl-XL. Displays no effect on the transactivational or cell cycle checkpoint control function of p53. Potentially increases reprogramming efficiency of human somatic cells to induced pluripotent stem cells (iPSCs) by silencing p53. Reduces cell death induced by γ -radiation in vitro and protects mice from doses of radiation that cause lethal hematopoietic syndrome. Selectively inhibits heat shock protein 70 (HSP70) activity. | [Biochem/physiol Actions]
Pifithrin-μ is an inhibitor of p53 binding and anti-apoptotic, which directly inhibits p53 binding to mitochondria as well as to Bcl-xL and Bcl-2 proteins. PFTμ rescues cells from lethal γ-irradiation-induced cell death. Because pifithrin-μ shuts down only the p53-mitochondrial pathway without affecting the transcriptional functions of p53, it is superior to pifithrin-α. | [Enzyme inhibitor]
This cell-permeable sulfonamide-based inhibitor and anti-apoptotic factor
(FW = 181.20 g/mol; CAS 64984-31-2; Solubility: >10 mg/mL DMSO, <2
mg/mL HO; pK = 8; Symbol = PFTμ and PAS), also known as 2-
2a
phenylethynesulfonamide, targets p53 and Heat Shock Protein-70, or HSP
70. Because it only targets the mitochondrial branch of the p53 pathway
without affecting the important transcriptional functions of p53, Pifithrin-μ
is recommended over Pifithrin-α for in vivo studies. PFTμ exhibits high
specificity for p53 and does not protect cells from apoptosis induced by
overexpression of the proapoptotic protein Bax or by treatment with
dexamethasone. With B-chronic lymphocytic leukemia (CLL) cells,
Pifithrin-μ (5–20 μM) initiated apoptosis within 24 hours, with maximal
death at 48 hours, as assessed by cell morphology, cleavage of poly (ADP-
ribose) polymerase (PARP), caspase-3 activation, and annexin V staining
. | [Enzyme inhibitor]
This synthetic Hsp70 protein substrate-binding inhibitor (FW = 181.21
g/mol; CAS 64984-31-2; Abbreviation: PES) selectively interacts with the
multifunctional, stress-inducible molecular chaperone HSP70, disrupting its
association with several of co-chaperones and client proteins. Treatment
of cultured tumor cells with PES promotes cell death as a consequence of
protein aggregation, impaired autophagy, and inhibition of lysosomal
function. (Typical does are 1–10 μg/g injected intraperitoneally in mice, and
1–10 μM in vitro.) PES also exerts profound effects both in vivo and in vitro
by: (a) preventing LPS-induced increase in serum alanine aminotransferase
(ALT) and aspartate aminotransferase (AST) activity, reducing infiltration
of inflammatory cells, and promoting liver cell apoptosis; (b) reducing
inducible nitric oxide synthase (iNOS) protein expression as well as that of
serum nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-6
(IL-6) content in LPS-stimulated mice; (c) decreasing the mRNA levels of
iNOS, TNF-α, and IL-6 in LPS-stimulated liver; (d) attenuating the
degradation of inhibitor of κB-α (IκB-α) as well as the phosphorylation and
nuclear translocation of nuclear factor-κB (NF-κB) in LPS-stimulated liver
. PES also r2+emarkably reduces typically observed increases in
intracellular [Ca] and intracellular pH value in LPS-stimulated RAW
264.7 cells. Moreover, PES significantly reduces the increase in Na+/H+
exchanger 1 (NHE1) association to Hsp70 in LPS-stimulated macrophages
and liver, suggesting that NHE1-Hsp70 interaction is required for the
involvement of NHE1 in the inflammation response. By disrupting HSP70
actions of in multiple cell signaling pathways, PES offers a way to probe
the diverse functions of this molecular. | [storage]
Store at -20°C,stored under nitrogen | [References]
1) Leu et al. (2009), The therapeutic potential of p53 reactivation by nutlin-3a in ALK+ anaplastic large cell lymphoma with wild-type or mutated p53; Mol. Cell, 36 15
2) Strom et al. (2006), Small-molecule inhibitor of p53 binding to mitochondria protects mice from gamma radiation.; Nat. Chem. Biol., 2 474 |
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