(R)-PFI-2 is a potent and selective inhibitor of SETD7 methyltransferase activity in cells

Proceedings of the National Academy of Sciences of the United States of America

Volumn 111, Issue 35, 2014, Pages 12853-12858

  Barsyte Lovejoy, Dalia ^a   Li, Fengling ^a   Oudhoff, Menno J ^b   Tatlock, John H ^c   Dong, Aiping ^a   Zeng, Hong ^a   Wu, Hong ^a   Freeman, Spencer A ^b   Schapira, Matthieu ^a   Senisterra, Guillermo A ^a   Kuznetsova, Ekaterina ^a   Marcellus, Richard ^d   Allali Hassani, Abdellah ^a   Kennedy, Steven ^a   Lambert, Jean Philippe ^e   Couzens, Amber L ^e   Aman, Ahmed ^d   Gingras, Anne Claude ^e,f   Al Awar, Rima ^a,d   Fish, Paul V ^g,i   Gerstenberger, Brian S ^c   Roberts, Lee ^c   Benn, Caroline L ^g   Grimley, Rachel L ^g   Braam, Mitchell J S ^b   Rossi, Fabio M V ^b   Sudol, Marius ^h   Brown, Peter J ^a   Bunnage, Mark E ^c   Owen, Dafydd R ^c   Zaph, Colby ^b   Vedadi, Masoud ^a   Arrowsmith, Cheryl H ^a,f   more..

^a UNIVERSITY OF TORONTO   (Canada)

^b UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^c PFIZER INC   (United States)

^d ONTARIO INSTITUTE FOR CANCER RESEARCH   (Canada)

^e MOUNT SINAI HOSPITAL   (Canada)

^f UNIVERSITY OF TORONTO   (Canada)

^g PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

^h WEIS CENTER FOR RESEARCH   (United States)

ⁱ UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

Chemical biology; Chemical probe; Epigenetics

Indexed keywords

CHEMICAL BIOLOGY; CHEMICAL PROBE; EPIGENETICS;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; DOSE-RESPONSE RELATIONSHIP, DRUG; ENZYME INHIBITORS; EPIGENESIS, GENETIC; FIBROBLASTS; HISTONE-LYSINE N-METHYLTRANSFERASE; HUMANS; MCF-7 CELLS; METHYLTRANSFERASES; MUTATION; PHOSPHOPROTEINS; PROTEIN STRUCTURE, TERTIARY; PROTEIN-SERINE-THREONINE KINASES; PYRROLIDINES; SIGNAL TRANSDUCTION; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONAMIDES; TETRAHYDROISOQUINOLINES;

EID: 84907228225     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1407358111     Document Type: Article

References (35)

1. Nishioka K, et al. (2002) Set9, a novel histone H3 methyltransferase that facilitates transcription by precluding histone tail modifications required for heterochromatin formation. Genes Dev 16(4):479-489.
2. Wang H, et al. (2001) Purification and functional characterization of a histone H3-lysine 4-specific methyltransferase. Mol Cell 8(6):1207-1217.
3. Calnan DR, et al. (2012) Methylation by Set9 modulates FoxO3 stability and transcriptional activity. Aging (Albany, NY) 4(7):462-479.
4. Carr SM, Munro S, Kessler B, Oppermann U, La Thangue NB (2011) Interplay between lysine methylation and Cdk phosphorylation in growth control by the retinoblastoma protein. EMBO J 30(2):317-327.
5. Chuikov S, et al. (2004) Regulation of p53 activity through lysine methylation. Nature 432(7015):353-360.
6. Deering TG, Ogihara T, Trace AP, Maier B, Mirmira RG (2009) Methyltransferase Set7/9 maintains transcription and euchromatin structure at islet-enriched genes. Diabetes 58(1):185-193.
7. Dhayalan A, Kudithipudi S, Rathert P, Jeltsch A (2011) Specificity analysis-based identification of new methylation targets of the SET7/9 protein lysine methyltransferase. Chem Biol 18(1):111-120.
8. Ea CK, Baltimore D (2009) Regulation of NF-kappaB activity through lysine monomethylation of p65. Proc Natl Acad Sci USA 106(45):18972-18977.
9. Estève PO, et al. (2009) Regulation of DNMT1 stability through SET7-mediated lysine methylation in mammalian cells. Proc Natl Acad Sci USA 106(13):5076-5081.
10. Keating ST, El-Osta A (2013) Transcriptional regulation by the Set7 lysine methyltransferase. Epigenetics 8(4):361-372.
11. Kouskouti A, Scheer E, Staub A, Tora L, Talianidis I (2004) Gene-specific modulation of TAF10 function by SET9-mediated methylation. Mol Cell 14(2):175-182.
12. Pagans S, et al. (2010) The cellular lysine methyltransferase Set7/9-KMT7 binds HIV-1 TAR RNA, monomethylates the viral transactivator Tat, and enhances HIV transcription. Cell Host Microbe 7(3):234-244.
13. Subramanian K, et al. (2008) Regulation of estrogen receptor alpha by the SET7 lysine methyltransferase. Mol Cell 30(3):336-347.
14. Wang J, et al. (2009) The lysine demethylase LSD1 (KDM1) is required for maintenance of global DNA methylation. Nat Genet 41(1):125-129.
15. Yang J, et al. (2010) Reversible methylation of promoter-bound STAT3 by histone-modifying enzymes. Proc Natl Acad Sci USA 107(50):21499-21504.
16. Yang XD, et al. (2009) Negative regulation of NF-kappaB action by Set9-mediated lysine methylation of the RelA subunit. EMBO J 28(8):1055-1066.
17. Campaner S, et al. (2011) The methyltransferase Set7/9 (Setd7) is dispensable for the p53-mediated DNA damage response in vivo. Mol Cell 43(4):681-688.
18. Lehnertz B, et al. (2011) p53-dependent transcription and tumor suppression are not affected in Set7/9-deficient mice. Mol Cell 43(4):673-680.
19. Schapira M (2011) Structural chemistry of human SET domain protein methyltransferases. Curr Chem Genomics 5(Suppl 1):85-94.
20. Li Y, et al. (2008) Role of the histone H3 lysine 4 methyltransferase, SET7/9, in the regulation of NF-kappaB-dependent inflammatory genes: Relevance to diabetes and inflammation. J Biol Chem 283(39):26771-26781.
21. Okabe J, et al. (2012) Distinguishing hyperglycemic changes by Set7 in vascular endothelial cells. Circ Res 110(8):1067-1076.
22. Garbino A, et al. (2009) Molecular evolution of the junctophilin gene family. Physiol Genomics 37(3):175-186.
23. Bunnage ME, Chekler EL, Jones LH (2013) Target validation using chemical probes. Nat Chem Biol 9(4):195-199.
24. Frye SV (2010) The art of the chemical probe. Nat Chem Biol 6(3):159-161.
25. Arrowsmith CH, Bountra C, Fish PV, Lee K, Schapira M (2012) Epigenetic protein families: A new frontier for drug discovery. Nat Rev Drug Discov 11(5):384-400.
26. Copeland RA, et al. (1995) Recombinant human dihydroorotate dehydrogenase: Expression, purification, and characterization of a catalytically functional truncated enzyme. Arch Biochem Biophys 323(1):79-86.
27. Ribeiro C, Esteves da Silva JC (2008) Kinetics of inhibition of firefly luciferase by oxyluciferin and dehydroluciferyl-adenylate. Photochem Photobiol Sci 7(9):1085-1090.
28. Xiao B, et al. (2003) Structure and catalytic mechanism of the human histone methyltransferase SET7/9. Nature 421(6923):652-656.
29. Ibáñez G, McBean JL, Astudillo YM, Luo M (2010) An enzyme-coupled ultrasensitive luminescence assay for protein methyltransferases. Anal Biochem 401(2):203-210.
30. Copeland RA (2013) Evaluation of Enzyme Inhibitors in Drug Discovery: A Guide for Medicinal Chemists and Pharmacologists (Wiley, Hoboken, NJ).
31. Oudhoff MJ, et al. (2013) Control of the hippo pathway by Set7-dependent methylation of Yap. Dev Cell 26(2):188-194.
32. Pan D (2010) The hippo signaling pathway in development and cancer. Dev Cell 19(4):491-505.
33. Vedadi M, et al. (2011) A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells. Nat Chem Biol 7(8):566-574.
34. Ferguson AD, et al. (2011) Structural basis of substrate methylation and inhibition of SMYD2. Structure 19(9):1262-1273.
35. Wigle TJ, Copeland RA (2013) Drugging the human methylome: An emerging modality for reversible control of aberrant gene transcription. Curr Opin Chem Biol 17(3):369-378.