Nonpeptidic propargylamines as inhibitors of lysine specific demethylase 1 (LSD1) with cellular activity

Journal of Medicinal Chemistry

Volumn 56, Issue 18, 2013, Pages 7334-7342

  Schmitt, Martin L ^a   Hauser, Alexander Thomas ^a   Carlino, Luca ^b   Pippel, Martin ^b   Schulz Fincke, Johannes ^a   Metzger, Eric ^c   Willmann, Dominica ^c   Yiu, Teresa ^d,e   Barton, Michelle ^e   Schüle, Roland ^c   Sippl, Wolfgang ^b   Jung, Manfred ^a  

^a UNIVERSITY OF FREIBURG   (Germany)

^b MARTIN LUTHER UNIVERSITY HALLE WITTENBERG   (Germany)

^c UNIVERSITY OF FREIBURG   (Germany)

^d BAYLOR COLLEGE OF MEDICINE   (United States)

^e UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 (N METHYL 4 PHENYLANILINO) 3 (PROP 2 YNYLAMINO)PROPAN 2 OL; 2 [(4 BIPHENYLOXY)METHYL]OXIRANE; 2',4' DICHLORO 4 PHENYLPHENOL; 3 (PROP 2 YNYLAMINO) 2 HYDROXY 1 (BIPHENYL 4 YLOXY)PROPANE; ANTINEOPLASTIC AGENT; LYSINE SPECIFIC DEMETHYLASE 1; METHYLTRANSFERASE; N METHYL 4 PHENYLANILINE; N METHYL N (OXIRAN 2 YLMETHYL) 4 PHENYLANILINE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; BREAST CANCER; CELL ACTIVITY; CELL PROLIFERATION; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; EPIGENETICS; IN VITRO STUDY;

AMINES; ANIMALS; CELL LINE, TUMOR; DRUG DESIGN; ENZYME INHIBITORS; HISTONE DEMETHYLASES; HISTONES; METHYLATION; MOLECULAR DOCKING SIMULATION; PROTEIN CONFORMATION;

EID: 84885013682     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm400792m     Document Type: Article

References (25)

1. Biel, M.; Wascholowski, V.; Giannis, A. Epigenetics-an epicenter of gene regulation: histones and histone-modifying enzymes Angew. Chem., Int. Ed. 2005, 44, 3186-3216 (Pubitemid 40778337)
2. Li, B.; Carey, M.; Workman, J. L. The role of chromatin during transcription Cell 2007, 128, 707-719 (Pubitemid 46273570)
3. Metzger, E.; Wissmann, M.; Yin, N.; Müller, J. M.; Schneider, R.; Peters, A. H.; Günther, T.; Buettner, R.; Schüle, R. LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription Nature 2005, 437, 436-439 (Pubitemid 41613508)
4. Shi, Y.; Lan, F.; Matson, C.; Mulligan, P.; Whetstine, J. R.; Cole, P. A.; Casero, R. A. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1 Cell 2004, 119, 941-953 (Pubitemid 40037608)
5. Stavropoulos, P.; Blobel, G.; Hoelz, A. Crystal structure and mechanism of human lysine-specific demethylase-1 Nat. Struct. Mol. Biol. 2006, 13, 626-632 (Pubitemid 44036473)
6. Lee, M. G.; Wynder, C.; Schmidt, D. M.; McCafferty, D. G.; Shiekhattar, R. Histone H3 lysine 4 demethylation is a target of nonselective antidepressive medications Chem. Biol. 2006, 13, 563-567
7. Suzuki, T.; Miyata, N. Lysine demethylases inhibitors J. Med. Chem. 2011, 54, 8236-8250
8. Culhane, J. C.; Szewczuk, L. M.; Liu, X.; Da, G.; Marmorstein, R.; Cole, P. A. A mechanism-based inactivator for histone demethylase LSD1 J. Am. Chem. Soc. 2006, 128, 4536-4537
9. Binda, C.; Valente, S.; Romanenghi, M.; Pilotto, S.; Cirilli, R.; Karytinos, A.; Ciossani, G.; Botrugno, O. A.; Forneris, F.; Tardugno, M.; Edmondson, D. E.; Minucci, S.; Mattevi, A.; Mai, A. Biochemical, structural, and biological evaluation of tranylcypromine derivatives as inhibitors of histone demethylases LSD1 and LSD2 J. Am. Chem. Soc. 2010, 132, 6827-6833
10. Benelkebir, H.; Hodgkinson, C.; Duriez, P. J.; Hayden, A. L.; Bulleid, R. A.; Crabb, S. J.; Packham, G.; Ganesan, A. Enantioselective synthesis of tranylcypromine analogues as lysine demethylase (LSD1) inhibitors Bioorg. Med. Chem. 2011, 19, 3709-3716
11. Ueda, R.; Suzuki, T.; Mino, K.; Tsumoto, H.; Nakagawa, H.; Hasegawa, M.; Sasaki, R.; Mizukami, T.; Miyata, N. Identification of cell-active lysine specific demethylase 1-selective inhibitors J. Am. Chem. Soc. 2009, 131, 17536-17537
12. Mimasu, S.; Umezawa, N.; Sato, S.; Higuchi, T.; Umehara, T.; Yokoyama, S. Structurally designed trans -2-phenylcyclopropylamine derivatives potently inhibit histone demethylase LSD1/KDM1 Biochemistry 2010, 49, 6494-6503
13. Huang, Y.; Greene, E.; Murray Stewart, T.; Goodwin, A. C.; Baylin, S. B.; Woster, P. M.; Casero, R. A., Jr. Inhibition of lysine-specific demethylase 1 by polyamine analogues results in reexpression of aberrantly silenced genes Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 8023-8028 (Pubitemid 47185869)
14. Zhu, Q.; Huang, Y.; Marton, L. J.; Woster, P. M.; Davidson, N. E.; Casero, R. A., Jr. Polyamine analogs modulate gene expression by inhibiting lysine-specific demethylase 1 (LSD1) and altering chromatin structure in human breast cancer cells Amino Acids 2012, 42, 887-898
15. Wang, J.; Lu, F.; Ren, Q.; Sun, H.; Xu, Z.; Lan, R.; Liu, Y.; Ward, D.; Quan, J.; Ye, T.; Zhang, H. Novel histone demethylase LSD1 inhibitors selectively target cancer cells with pluripotent stem cell properties Cancer Res. 2011, 71, 7238-7249
16. Willmann, D.; Lim, S.; Wetzel, S.; Metzger, E.; Jandausch, A.; Wilk, W.; Jung, M.; Forne, I.; Imhof, A.; Janzer, A.; Kirfel, J.; Waldmann, H.; Schule, R.; Buettner, R. Impairment of prostate cancer cell growth by a selective and reversible LSD1 inhibitor Int. J. Cancer 2012, 131, 2704-2709
17. Hauser, A.-T.; Bissinger, E.-M.; Metzger, E.; Repenning, A.; Bauer, U.-M.; Mai, A.; Schüle, R.; Jung, M. Screening assays for epigenetic targets using native histones as substrates J. Biomol. Screening 2012, 17, 18-26
18. Yang, M.; Culhane, J. C.; Szewczuk, L. M.; Jalili, P.; Ball, H. L.; Machius, M.; Cole, P. A.; Yu, H. Structural basis for the inhibition of the LSD1 histone demethylase by the antidepressant trans-2-phenylcyclopropylamine Biochemistry 2007, 46, 8058-8065 (Pubitemid 47051641)
19. Chen, Y. Crystal structure of human histone lysine-specific demethylase 1 (LSD1) Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 13956-13961 (Pubitemid 44452964)
20. Forneris, F.; Binda, C.; Adamo, A.; Battaglioli, E.; Mattevi, A. Structural basis of LSD1-CoREST selectivity in histone H3 recognition J. Biol. Chem. 2007, 282, 20070-20074 (Pubitemid 47099979)
21. Yang, M.; Gocke, C. B.; Luo, X.; Borek, D.; Tomchick, D. R.; Machius, M.; Otwinowski, Z.; Yu, H. Structural basis for CoREST-dependent demethylation of nucleosomes by the human LSD1 histone demethylase Mol. Cell 2006, 23, 377-387 (Pubitemid 44128856)
22. Mimasu, S.; Sengoku, T.; Fukuzawa, S.; Umehara, T.; Yokoyama, S. Crystal structure of histone demethylase LSD1 and tranylcypromine at 2.25 A Biochem. Biophys. Res. Commun. 2008, 366, 15-22 (Pubitemid 50007727)
23. Yang, M.; Culhane, J. C.; Szewczuk, L. M.; Gocke, C. B.; Brautigam, C. A.; Tomchick, D. R.; Machius, M.; Cole, P. A.; Yu, H. Structural basis of histone demethylation by LSD1 revealed by suicide inactivation Nat. Struct. Mol. Biol. 2007, 14, 535-539 (Pubitemid 46871816)
24. Culhane, J. C.; Cole, P. A. LSD1 and the chemistry of histone demethylation Curr. Opin. Chem. Biol. 2007, 11, 561-568 (Pubitemid 47588999)
25. Fraaije, M. W.; Mattevi, A. Flavoenzymes: diverse catalysts with recurrent features Trends Biochem. Sci. 2000, 25, 126-132