60477-38-5 Usage
Description
Pifithrin-α, p-nitro, cyclic is a cell-permeable p53 inhibitor that is derived from the compound Pifithrin-α. It is characterized by its higher potency and longer half-life compared to the standard Pifithrin-α. Pifithrin-α, p-nitro, cyclic is designed to block p53-dependent transcriptional activation and apoptosis, making it a potential candidate for anti-cancer applications.
Uses
Used in Pharmaceutical Industry:
Pifithrin-α, p-nitro, cyclic is used as an inactivator of p53 for its ability to block p53-dependent transcriptional activation and apoptosis. This makes it a potential anti-cancer agent, particularly in the development of treatments targeting p53-related pathways in cancer cells.
However, it is important to note that while Pifithrin-α, p-nitro, cyclic shows in vitro efficacy, it is not effective when administered in rats in vivo. For in vivo applications, alternative compounds such as Pifithrin-α, p-Nitro (Cat. No. 506152) should be considered.
Biological Activity
p-nitro-cyclic pifithrin-α is an inactivator of p53.the activation of the tumor suppressor gene p53 plays a key role in regulating the in-vitro death of neurons, following apoptotic stimuli molecules including glutamate and dna-damaging agents. thus, p53 inhibitors may prove effective in suppressing the degenerative processes in neurodegenerative disorders.
Biochem/physiol Actions
Cell permeable: yes
in vitro
pifithrin-α (pft-α) was identified as an inactivator of p53 blocking p53-dependent transcriptional activation and apoptosis. cyclic pft-α was a stable analog of pft-α. p-nitro-cyclic pft-α, a cell-permeable form of cyclic pft-α, was found to be one order of magnitude more active than pft-α in protecting cortical neurons exposed to etoposide. p-nitro-cyclic pft-α acted in a p53-dependently but did not block phosphorylation of p53 on ser15 in response to etoposide treatment, although it prevented p53 posttranscriptional activity [1].
in vivo
in a previou study, c57bl/6 mice were fed a high-fat (hfd) or control diet for 8 weeks; pft was administered three times per week. results showed that pft administration could suppress hfd-induced weight gain, steatosis, oxidative stress, alt elevation, and apoptosis. pft treatment also able to blunt the hfd-induced upregulation of mirna34a and increase sirt1 expression. in the livers of hfd-fed, pft-treated mice, activation of the sirt1/pgc1α/pparα axis increased the expression of malonyl-coa decarboxylase [2].
references
[1] . pietrancosta, n.,moumen, a.,dono, r., et al. imino-tetrahydro-benzothiazole derivatives as p53 inhibitors: discovery of a highly potent in vivo inhibitor and its action mechanism. journal of medicinal chemistry 49(12), 3645-3652 (2006).[2] derdak z, villegas ka, harb r, wu am, sousa a, wands jr. inhibition of p53 attenuates steatosis and liver injury in a mouse model of non-alcoholic fatty liver disease. j hepatol. 2013 apr;58(4):785-91.
Check Digit Verification of cas no
The CAS Registry Mumber 60477-38-5 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 6,0,4,7 and 7 respectively; the second part has 2 digits, 3 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 60477-38:
(7*6)+(6*0)+(5*4)+(4*7)+(3*7)+(2*3)+(1*8)=125
125 % 10 = 5
So 60477-38-5 is a valid CAS Registry Number.
60477-38-5Relevant articles and documents
Identification of new aminoacid amides containing the imidazo[2,1-b] benzothiazol-2-ylphenyl moiety as inhibitors of tumorigenesis by oncogenic Met signaling
Furlan, Alessandro,Colombo, Francesco,Kover, Andrea,Issaly, Nathalie,Tintori, Cristina,Angeli, Lucilla,Leroux, Vincent,Letard, Sébastien,Amat, Mercedes,Asses, Yasmine,Maigret, Bernard,Dubreuil, Patrice,Botta, Maurizio,Dono, Rosanna,Bosch, Joan,Piccolo, Oreste,Passarella, Daniele,Maina, Flavio
, p. 239 - 254 (2012/03/08)
The Met receptor tyrosine kinase is a promising target in anticancer therapies for its role during tumor evolution and resistance to treatment. It is characterized by an unusual structural plasticity as its active site accepts different inhibitor binding
Imino-tetrahydro-benzothiazole derivatives as p53 inhibitors: Discovery of a highly potent in vivo inhibitor and its action mechanism
Pietrancosta, Nicolas,Moumen, Anice,Dono, Rosanna,Lingor, Paul,Planchamp, Veronique,Lamballe, Fabienne,B?hr, Mathias,Kraus, Jean-Louis,Maina, Flavio
, p. 3645 - 3652 (2007/10/03)
Several neurological disorders manifest symptoms that result from the degeneration and death of specific neurons. p53 is an important modulator of cell death, and its inhibition could be a therapeutic approach to several neuropathologies. Here, we report
