产品号 #72062_C
p53 Inhibitor
概述
Cyclic Pifthrin-Alpha is a cell-permeable and reversible inhibitor of p53-mediated apoptosis and p53-dependent gene transcription. It is a more stable and less cytotoxic analog of the non-cyclic form of pifithrin-alpha. Cyclic Pifithrin-Alpha has also been reported to activate the aryl hydrocarbon receptor (Fernandez-Cruz et al., Gary & Jensen, Komarov et al.)
REPROGRAMMING
· Increases efficiency of reprogramming mouse embryonic fibroblasts to induced pluripotent stem cells (Liao et al.).
MAINTENANCE AND SELF-RENEWAL
· Reduces UV-induced apoptosis of mouse embryonic stem cells (Qin et al.).
· Increases the numbers of mouse hematopoietic stem and progenitor cells in vivo and in vitro, also decreases the radiation-induced death of these cells (Leonova et al.).
Alternative Names
Cyclic PFT-α, Cyclic Pifithrin-α, PFT-β, Pifithrin-β
Cell Type
Hematopoietic Stem and Progenitor Cells, Pluripotent Stem Cells
Species
Human, Mouse, Non-Human Primate, Other, Rat
Application
Expansion, Maintenance, Reprogramming
Area of Interest
Stem Cell Biology
CAS Number
511296-88-1
Chemical Formula
C₁₆H₁₆N₂S · HBr
Molecular Weight
349.3 g/mol
Purity
≥ 95%
Pathway
p53
Target
p53
Protocols and Documentation
Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.
Applications
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Resources and Publications
Educational Materials (3)
Publications (6)
Inhibition of PTEN tumor suppressor promotes the generation of induced pluripotent stem cells. Molecular therapy : the journal of the American Society of Gene Therapy 2013 JUN
Abstract
Induced pluripotent stem cells (iPSCs) can be generated from patients with specific diseases by the transduction of reprogramming factors and can be useful as a cell source for cell transplantation therapy for various diseases with impaired organs. However, the low efficiency of iPSC derived from somatic cells (0.01-0.1%) is one of the major problems in the field. The phosphoinositide 3-kinase (PI3K) pathway is thought to be important for self-renewal, proliferation, and maintenance of embryonic stem cells (ESCs), but the contribution of this pathway or its well-known negative regulator, phosphatase, and tensin homolog deleted on chromosome ten (Pten), to somatic cell reprogramming remains largely unknown. Here, we show that activation of the PI3K pathway by the Pten inhibitor, dipotassium bisperoxo(5-hydroxypyridine-2-carboxyl)oxovanadate, improves the efficiency of germline-competent iPSC derivation from mouse somatic cells. This simple method provides a new approach for efficient generation of iPSCs.
Biological and chemical studies on aryl hydrocarbon receptor induction by the p53 inhibitor pifithrin-α and its condensation product pifithrin-β. Life sciences 2011 APR
Abstract
AIMS Pifithrin α (PFTα), an inhibitor of the p53 protein, is regarded as a lead compound for cancer and neurodegenerative disease therapy. There is some evidence that this compound activates the aryl hydrocarbon receptor (AhR) in a complete independent way of the p53 inhibition and that it is easily converted to its condensation product pifithrin β (PFTβ). The aim of this study was to explore the ability of PFTα and of PFTβ to induce a variety of AhR mediated processes. MAIN METHODS Computational analysis using quantum chemical calculations and chemical analysis have been used to study the conformation of the compounds as well as the cyclization reaction. The AhR mediated processes of these compounds have been studied in a rainbow trout cell line (RTG-2) and in a rat hepatoma cell line (H4IIE). KEY FINDINGS PFTα molecule could not take a planar conformation required for AhR activation whereas PFTβ showed a conformation similar to those of the prototypical AhR ligand β-naphthoflavone. In both cell lines, PFTα and PFTβ provoked different responses related with AhR activation. However, when cyclization of PFTα to PFTβ was hampered by acetylation of the exocyclic nitrogen, all these responses were not observed. These results lead to the conclusion that the activation of the AhR is probably caused by PFTβ instead of PFTα. SIGNIFICANCE Since PFTα is a promising compound for the development of new pharmaceuticals inhibiting p53, the chemical instability of this compound as well as the capacity of its transformation product should be taken into account.
A small molecule inhibitor of p53 stimulates amplification of hematopoietic stem cells but does not promote tumor development in mice. Cell cycle (Georgetown, Tex.) 2010 APR
Abstract
It has been shown that genetic inhibition of p53 leads to enhanced proliferation of hematopoietic stem cells (HSCs). This could, in theory, contribute to the increased frequency of tumor development observed in p53-deficient mice and humans. In our previous work, we identified chemical p53 inhibitors (PFTs) that suppress the transactivation function of p53 and protect cultured cells and mice from death induced by gamma irradiation (IR). Here we found that when applied to bone marrow cells in vitro or injected into mice, PFTb impeded IR-induced reduction of hematopoietic stem cell (HSC) and hematopoietic progenitor cell (HPC) population sizes. In addition, we showed that PFTb stimulated HSC and HPC proliferation in the absence of IR in vitro and in vivo and mobilized HSCs to the peripheral blood. Importantly, however, PFTb treatment did not affect the timing or frequency of tumor development in irradiated p53 heterozygous mice used as a model for determination of carcinogenicity. Thus, although PFTb administration led to increased numbers of HSCs and HPCs, it was not carcinogenic in mice. These findings suggest that chemical p53 inhibitors may be clinically useful as safe and effective stimulators of hematopoiesis.
PRODUCTS ARE FOR RESEARCH USE ONLY AND NOT INTENDED FOR HUMAN OR ANIMAL DIAGNOSTIC OR THERAPEUTIC USES UNLESS OTHERWISE STATED.
