64984-31-2 Usage
Description
PHENYLETHYNSULFONIC ACID AMIDE, also known as Pifithrin-μ (PFT-μ), is a small molecule inhibitor of p53-mediated apoptosis. It prevents p53 binding to anti-apoptotic proteins Bcl-xL and Bcl-2 at the mitochondria without affecting p53 transactivational activities. PFT-μ has a binding affinity for both p53 (Kd = 0.82 mM) and Bcl-xL (Kd = 0.80 mM). It has been shown to reduce p53-mediated apoptosis induced by γ-radiation in mouse thymocytes in vitro and protect mice from doses of radiation that cause lethal hematopoietic syndrome.
Uses
Used in Radiation Protection:
PHENYLETHYNSULFONIC ACID AMIDE is used as a small molecule inhibitor of p53 binding to mitochondria for protecting mice from gamma radiation.
Used in Neuroprotection Research:
PHENYLETHYNSULFONIC ACID AMIDE is used as a treatment for microglial cell lines to analyze its neuroprotective effect on M1-like and M2-like phenotypes.
Used in Heat Shock Protein Inhibition:
PHENYLETHYNSULFONIC ACID AMIDE is used as a heat shock protein (HSP)-70 inhibitor for treating transfected Marc-145 cells to elucidate the role of heat shock chaperones in mouse embryonic stem cells.
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 H2O; pKa = 8; Symbol = PFTμ and PAS), also known as 2- 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(ADPribose) polymerase (PARP), caspase-3 activation, and annexin V staining.
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
Check Digit Verification of cas no
The CAS Registry Mumber 64984-31-2 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 6,4,9,8 and 4 respectively; the second part has 2 digits, 3 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 64984-31:
(7*6)+(6*4)+(5*9)+(4*8)+(3*4)+(2*3)+(1*1)=162
162 % 10 = 2
So 64984-31-2 is a valid CAS Registry Number.
InChI:InChI=1/C8H7NO2S/c9-12(10,11)7-6-8-4-2-1-3-5-8/h1-5H,(H2,9,10,11)
64984-31-2Relevant articles and documents
Novel improved synthesis of hsp70 inhibitor, pifithrin-μ in vitro synergy quantification of pifithrin-μ combined with pt drugs in prostate and colorectal cancer cells
McKeon, Aoife M.,Egan, Alan,Chandanshive, Jay,McMahon, Helena,Griffith, Darren M.
, (2016)
We describe a novel improved approach to the synthesis of the important and well-known heat shock protein 70 inhibitor (HSP70), pifithrin-μ, with corresponding and previously unreported characterisation. The first example of a combination study comprising
HSP70 INHIBITORS AND METHODS OF USING SAME
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Page/Page column 67; 73-74, (2021/10/11)
The disclosure provides compounds, and compositions comprising such compounds, that can be used to treat cancer, especially colorectal cancer (CRC). In certain embodiments, the compounds of the disclosure inhibit HSP70. In other embodiments, the compounds of the disclosure promote or increase immune cell recruitment to a cancer. In yet other embodiments, the compounds of the disclosure promote or increase immune cell infiltration in a cancer.
