Identification of a small molecule 1,4-bis-[4-(3-phenoxy-propoxy)-but-2- ynyl]-piperazine as a novel inhibitor of the transcription factor p53

Acta Pharmacologica Sinica

Volumn 34, Issue 6, 2013, Pages 805-810

  Liu, Xin ^a   Zhang, Ying ^b   Tong, Man ^a   Liu, Xiu Ying ^a,c   Luo, Guan Zheng ^a   Xie, Dong Fang ^a   Ren, Shao Fang ^a   Bai, Dong Hui ^b,c   Wang, Liu ^b   Zhou, Qi ^b   Wang, Xiu Jie ^a  

^a INSTITUTE OF GENETICS AND DEVELOPMENTAL BIOLOGY   (China)

^b INSTITUTE OF ZOOLOGY   (China)

^c UNIVERSITY OF CHINESE ACADEMY OF SCIENCES   (China)

Author keywords

1,4 bis 4 (3 phenoxy propoxy) but 2 ynyl piperazine; embryonic fibroblast; embryonic stem cell; p53; p53 inhibitor; proliferation; tumor suppressor protein

Indexed keywords

1,4 BIS [4 (3 PHENOXY PROPOXY)BUT 2 YNYL]PIPERAZINE; MESSENGER RNA; PIPERAZINE DERIVATIVE; PROTEIN MDM2; PROTEIN P21; PROTEIN P53; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CELL PROLIFERATION; CONTROLLED STUDY; DOWN REGULATION; EMBRYONIC STEM CELL; FIBROBLAST; GENE EXPRESSION PROFILING; MOUSE; NONHUMAN; PROTEIN EXPRESSION; REAL TIME POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; UPREGULATION; WESTERN BLOTTING;

ANIMALS; BLOTTING, WESTERN; CELL PROLIFERATION; CELLS, CULTURED; DOWN-REGULATION; EMBRYONIC STEM CELLS; FIBROBLASTS; MICE; PHENYL ETHERS; PIPERAZINES; REAL-TIME POLYMERASE CHAIN REACTION; RNA, MESSENGER; SIGNAL TRANSDUCTION; TIME FACTORS; TUMOR SUPPRESSOR PROTEIN P53; UP-REGULATION;

EID: 84881454561     PISSN: 16714083     EISSN: 17457254     Source Type: Journal    
DOI: 10.1038/aps.2013.61     Document Type: Article

References (32)

1. Vousden KH, Prives C. Blinded by the light: the growing complexity of p53. Cell 2009; 137: 413-31.
2. Vogelstein B, Lane D, Levine AJ. Surfing the p53 network. Nature 2000; 408: 307-10.
3. Vousden KH, Lu X. Live or let die: the cell's response to p53. Nat Rev Cancer 2002; 2: 594-604.
4. Li M, He Y, Dubois W, Wu X, Shi J, Huang J. Distinct regulatory mechanisms and functions for p53-activated and p53-repressed DNA damage response genes in embryonic stem cells. Mol Cell 2012; 46: 30-42.
5. Hong H, Takahashi K, Ichisaka T, Aoi T, Kanagawa O, Nakagawa M, et al. Suppression of induced pluripotent stem cell generation by the p53-p21 pathway. Nature 2009; 460: 1132-5.
6. Li M, Huang J. A new puzzling role of p53 in mouse embryonic stem cells. Cell Cycle 2010; 9: 1669-70.
7. Lin T, Chao C, Saito S, Mazur SJ, Murphy ME, Appella E, et al. p53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression. Nat Cell Biol 2005; 7: 165-71.
8. Maimets T, Neganova I, Armstrong L, Lako M. Activation of p53 by nultin leads to rapid differentiation of human embryonic stem cells. Oncogene 2008; 27: 5277-87.
9. Qin H, Yu T, Qing T, Liu Y, Zhao Y, Cai J, et al. Regulation of apoptosis and differentiation by p53 in human embryonic stem cells. J Biol Chem 2007; 282: 5842-52.
10. Marion RM, Strati K, Li H, Murga M, Blanco R, Ortega S, et al. A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity. Nature 2009; 460: 1149-53.
11. Zhao Y, Yin X, Qin H, Zhu F, Liu H, Yang W, et al. Two supporting factors greatly improve the efficiency of human iPSC generation. Cell Stem Cell 2008; 3: 475-9.
12. Bykov VJN, Selivanova G, Wiman KG. Small molecules that reactivate mutant p53. Eur J Cancer 2003; 39: 1828-34.
13. Wiman KG. Strategies for therapeutic targeting of the p53 pathway in cancer. Cell Death Differ 2006; 13: 921-6.
14. Nayak SK, Panesar PS, Kumar H. p53-induced apoptosis and inhibitors of p53. Curr Med Chem 2009; 16: 2627-40.
15. Asher G, Lotem J, Cohen B, Sachs L, Shaul Y. Regulation of p53 stability and p53-dependent apoptosis by NADH quinone oxidoreductase 1. Proc Natl Acad Sci USA 2001; 98: 1188-93.
16. Asher G, Lotem J, Kama R, Sachs L, Shaul Y. NQO1 stabilizes p53 through a distinct pathway. Proc Natl Acad Sci USA 2002; 99: 3099-104.
17. Asher G, Lotem J, Sachs L, Kahana C, Shaul Y. Mdm-2 and ubiquitinindependent p53 proteasomal degradation regulated by NQO1. Proc Natl Acad Sci USA 2002; 99: 13125-30.
18. Komarov PG, Komarova EA, Kondratov RV, Christov-Tselkov K, Coon JS, Chernov MV, et al. A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy. Science 1999; 285: 1733-7.
19. Komarova EA, Gudkov AV. Suppression of p53: a new approach to overcome side effects of antitumor therapy. Biochemistry 2000; 65: 41-8.
20. Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 2004; 303: 844-8.
21. Abdelalim EM, Tooyama I. The p53 inhibitor, pifithrin-?, suppresses self-renewal of embryonic stem cells. Biochem Biophys Res Commun 2012; 420: 605-10.
22. Tong M, Lv Z, Liu L, Zhu H, Zheng QY, Zhao XY, et al. Mice generated from tetraploid complementation competent iPS cells show similar developmental features as those from ES cells but are prone to tumorigenesis. Cell Res 2011; 21: 1634-7.
23. Zhao XY, Li W, Lv Z, Liu L, Tong M, Hai T, et al. iPS cells produce viable mice through tetraploid complementation. Nature 2009; 461: 86-90.
24. Wu H, Chen Y, Liang J, Shi B, Wu G, Zhang Y, et al. Hypomethylationlinked activation of PAX2 mediates tamoxifen-stimulated endometrial carcinogenesis. Nature 2005; 438: 981-7.
25. Plasilova M, Schonmeyr B, Fernandez J, Clavin N, Soares M, Mehrara BJ. Accelerating stem cell proliferation by down-regulation of cell cycle regulator p21. Plast Reconstr Surg 2009; 123: 149S-157S.
26. Sandberg M, Källström M, Muhr J. Sox21 promotes the progression of vertebrate neurogenesis. Nat Neurosci 2005; 8: 995-1001.
27. Bourillot PY, Savatier P. Krüppel-like transcription factors and control of pluripotency. BMC Biol 2010; 8: 125.
28. Tutter AV, Kowalski MP, Baltus GA, Iourgenko V, Labow M, Li E, et al. Role for Med12 in regulation of Nanog and Nanog target genes. J Biol Chem 2009; 284: 3709-18.
29. Macleod KF, Sherry N, Hannon G, Beach D, Tokino T, Kinzler K, et al. p53-dependent and independent expression of p21 during cell growth, differentiation, and DNA damage. Genes Dev 1995; 9: 935-44.
30. Huo JX, Metz SA, Li GD. p53-independent induction of p21waf1/cip1 contributes to the activation of caspases in GTP-depletion-induced apoptosis of insulin-secreting cells. Cell Death Differ 2004; 11: 99-109.
31. Aliouat-Denis CM, Dendouga N, Van den Wyngaert I, Goehlmann H, Steller U, van de Weyer I, et al. p53-independent regulation of p21Waf1/Cip1 expression and senescence by Chk2. Mol Cancer Res 2005; 3: 627-34.
32. Hall J, Guo G, Wray J, Eyres I, Nichols J, Grotewold L, et al. Oct4 and LIF/Stat3 additively induce Krüppel factors to sustain embryonic stem cell self-renewal. Cell Stem Cell 2009; 5: 597-609.