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- Pifithrin-α (PFTα)
Pifithrin-α (PFTα)
Pifithrin-α is a synthetic, water-soluble and stable inhibitor of p53 [1].
Pifithrin-α is firstly found to block the activation of p53-responsive lacZ in ConA cells and reduce activation of endogenous cellular p53-responsive genes. In MEF cells transformed with E1a+ras, 10 μM Pifithrin-α can inhibit the apoptosis of the cells and this anti-apoptotic activity is p53-dependent. Pifithrin-α also inhibits the growth arrest of human diploid fibroblasts induced by DNA damage but has no effect on p53-deficient fibroblasts. In addition, Pifithrin-α induces G2-arrest of cells after gamma irradiation [1].
Moerover, Pifithrin-α can also induce cell cycle arrest and growth arrest of embryonic stem cells. Treatment of Pifithrin-α significantly downregulates the protein lever of Nanog (a pluripotency marker).It is proved that the inhibition of p53 activity caused by Pifithrin-α has no effect on ES cell viability [2].
References:
[1] Komarov PG, Komarova EA, Kondratov RV, Christov-Tselkov K, Coon JS, Chernov MV, Gudkov AV. A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy. Science. 1999 Sep 10; 285 (5434): 1733-7.
[2] Abdelalim EM, Tooyama I. The p53 inhibitor, pifithrin-α, suppresses self-renewal of embryonic stem cells. Biochem Biophys Res Commun. 2012 Apr 13; 420 (3): 605-10.
- 1. Cong-cong Wang, Wen-bin Liu, et al. "Excess DHA Induces Cell Cycle Arrest by Activating the P53/Cycling Pathway in Blunt Snout Bream (Megalobrama amblycephala)." ORIGINAL RESEARCH. 15 May, 2020.
- 2. He W, Tao W, et al. "Lobetyolin induces apoptosis of colon cancer cells by inhibiting glutamine metabolism." J Cell Mol Med. 2020;10.1111/jcmm.15009. PMID:31990147
- 3. Xie YL, Zhang B, Jing L. "MiR-125b blocks Bax/Cytochrome C/Caspase-3 apoptotic signaling pathway in rat models of cerebral ischemia-reperfusion injury by targeting p53." Neurol Res. 2018 Jun 29:1-10. PMID:29956588
- 4. Guo XB, Deng X, et al. "Hematopoietic Substrate-1-Associated Protein X-1 Regulates the Proliferation and Apoptosis of Endothelial Progenitor Cells Through Akt Pathway Modulation." Stem Cells. 2018 Mar;36(3):406-419. PMID:29139175
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 367.3 |
| Cas No. | 63208-82-2 |
| Formula | C16H18N2OS·HBr |
| Solubility | insoluble in H2O; ≥17.45 mg/mL in DMSO; ≥7.12 mg/mL in EtOH with gentle warming and ultrasonic |
| Chemical Name | 2-(2-imino-4,5,6,7-tetrahydro-1,3-benzothiazol-3-yl)-1-(4-methylphenyl)ethanone;hydrobromide |
| SDF | Download SDF |
| Canonical SMILES | CC1=CC=C(C=C1)C(=O)CN2C3=C(CCCC3)SC2=N.Br |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
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Cell lines |
Murine embryonic stem (ES) cells |
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Preparation method |
The solubility of this compound in DMSO is >17.45 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37°C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months. |
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Reacting condition |
10 μM and 20 μM; 24 or 48 h |
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Applications |
In murine ES cells, pifithrin-α significantly reduced the number and colony size of the ES cells in a dose dependent way. In ES cells seeded at low density in the presence of LIF, pifithrin-α significantly reduced the number of formed secondary ES cell colonies. |
| Animal experiment [2]: | |
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Animal models |
Balb/c and C57BL6 mice treated with whole-body gamma irradiation |
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Dosage form |
2.2 mg/kg; i.p. injection |
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Application |
In Balb/c and C57BL6 mice treated with whole-body gamma irradiation, pifithrin-α completely rescued mice of both strains from 60% killing doses of gamma irradiation (8 Gy for C57BL and 6 Gy for Balb/c). pifithrin-α did not protect p53-null mice from lethal irradiation, suggesting that pifithrin-α acted through a p53-dependent way. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Abdelalim EM, Tooyama I. The p53 inhibitor, pifithrin-α, suppresses self-renewal of embryonic stem cells. Biochem Biophys Res Commun. 2012 Apr 13; 420 (3): 605-10. [2] Komarov PG, Komarova EA, Kondratov RV, Christov-Tselkov K, Coon JS, Chernov MV, Gudkov AV. A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy. Science. 1999 Sep 10; 285 (5434): 1733-7. |
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| Description | Pifithrin-α is an inactivator of p53 | |||||
| Targets | p53 | |||||
| IC50 | ||||||
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