| Identification | Back Directory | [Name]
Pifithrin-α, p-nitro, cyclic | [CAS]
60477-38-5 | [Synonyms]
p-Nitro-CyclicPifithrin-α
p-nitro-Cyclic Pifithrin-α
Cyclic pifithrin-α-p-nitro
p-Nitro-Cyclic Pifithrin-a
Pifithrin-α, p-nitro, cyclic
p-nitro Cyclic Pifithrin-.alpha.
Pifithrin-alpha, p-Nitro, Cyclic
Pifithrin-α, p-Nitro, Cyclic - CAS 60477-38-5 - Calbiochem
Imidazo[2,1-b]benzothiazole, 5,6,7,8-tetrahydro-2-(4-nitrophenyl)-
2-(4-Nitro-phenyl)-5,6,7,8-tetrahydro-benzo[d]imidazo[2,1-b]thiazole | [Molecular Formula]
C15H13N3O2S | [MOL File]
60477-38-5.mol | [Molecular Weight]
299.35 |
| Chemical Properties | Back Directory | [Melting point ]
233-234 °C(Solv: N,N-dimethylformamide (68-12-2); water (7732-18-5)) | [density ]
1.53±0.1 g/cm3(Predicted) | [storage temp. ]
-20C | [solubility ]
≤1mg/ml in dimethyl formamide | [form ]
Yellow solid | [pka]
6.14±0.20(Predicted) | [color ]
Light yellow to yellow | [InChI]
1S/C15H13N3O2S/c19-18(20)11-7-5-10(6-8-11)12-9-17-13-3-1-2-4-14(13)21-15(17)16-12/h5-9H,1-4H2 | [InChIKey]
XMFNSEDROOHGBY-UHFFFAOYSA-N | [SMILES]
[s]1c2[n](c4c1CCCC4)cc(n2)c3ccc(cc3)[N+](=O)[O-] |
| Hazard Information | Back Directory | [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. |
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