60477-38-5

Basic information

• Product Name: Pifithrin-α, p-nitro, cyclic
• Synonyms: Pifithrin-α, p-nitro, cyclic;p-nitro-Cyclic Pifithrin-α;Pifithrin-alpha, p-Nitro, Cyclic;2-(4-Nitro-phenyl)-5,6,7,8-tetrahydro-benzo[d]imidazo[2,1-b]thiazole;p-nitro Cyclic Pifithrin-.alpha.
• CAS NO: 60477-38-5
• Molecular Formula: C₁₅H₁₃N₃O₂S
• Molecular Weight: 299.34762
• Mol File: 60477-38-5.mol
• Article Data: 4

Chemical Properties

• Melting Point: 233-234 °C(Solv: N,N-dimethylformamide (68-12-2); water (7732-18-5))
• Appearance: /
• Density: 1.53±0.1 g/cm3(Predicted)
• Storage Temp.: -20C
• Solubility: ≤1mg/ml in dimethyl formamide
• PKA: 6.14±0.20(Predicted)
• CAS DataBase Reference: Pifithrin-α, p-nitro, cyclic(CAS DataBase Reference)
• NIST Chemistry Reference: Pifithrin-α, p-nitro, cyclic(60477-38-5)
• EPA Substance Registry System: Pifithrin-α, p-nitro, cyclic(60477-38-5)

Safety Data

• Hazardous Substances Data: 60477-38-5(Hazardous Substances Data)

Usage

Uses

p-nitro-Cyclic Pifithrin-α is an inactivator of p53 that blocks p53-dependent transcriptional activation and apoptisis. Anti-cancer agent.

General Description

A cell-permeable p53 inhibitor that exhibits 10-fold higher potency (ED50 = 30 nM in protecting etoposide-induced cortical neuron death) and 50% longer half-life (t1/2 = 6h in neuron culture medium at 37°C) than Pifithrin-α (Cat. No. 506132). However, despite its in vitro efficacy, this inhibitor is not effective when adminstered in rats in vivo. For in vivo applications, please consider Pifithrin-α, p-Nitro (Cat. No. 506152).

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.

Upstream product

• 2933-29-1 2-Amino-4,5,6,7-tetrahydrobenzothiazole 
• 118926-63-9 2-amino-4,5,6,7-tetrahydrobenzothiazole hydroiodide 
• 108-94-1 cyclohexanone 
• 99-81-0 4-Nitrophenacyl bromide 

Downstream Products

• 1282523-77-6 4-(5,6,7,8-tetrahydroimidazo[2,1-b]benzothiazol-2-yl)benzenamine hydrochloride 
• 1356955-74-2 CF₀₅₄ 

Relevant 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

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

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