Epigenetic Targets in Drug Discovery, Volume 42 - download pdf or read online
By Wolfgang Sippl, Manfred Jung, Raimund Mannhold, Hugo Kubinyi, Gerd Folkers
ISBN-10: 3527323554
ISBN-13: 9783527323555
ISBN-10: 3527627073
ISBN-13: 9783527627073
Fueled by way of the services of a crew of foreign professional authors, this primary reference at the booming subject covers every little thing a drug researcher must learn about focusing on epigenetic mechanisms of affliction.
the 1st a part of the publication surveys present methodologies for locating and validating drug applicants that act through epigenetic mechanisms. the second one half systematically surveys identified and suspected drug pursuits in the epigenetic equipment, together with the invention and improvement of vorinostat, the 1st advertised epigenetic drug.
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Extra resources for Epigenetic Targets in Drug Discovery, Volume 42
Example text
For example, RG108 (3), a phthaloyl tryptophan derivative was identified in a small molecule screen as a DNMT1 active site inhibitor [75]. RG108 inhibits methyltransferase activity in vitro and reduces global methylation levels in human cancer cells [76]. Hydralazine (4), a vasodilating drug, is reported to inhibit DNA methylation [77]. Surprisingly, in a recent Phase I study, hydralazine reactivated tumor suppressor genes in cervical cancer patients without altering global methylation levels [78].
ACS Chemical Biology, 1, 433–441. K. M. (1999) Structure and ligand of a histone acetyltransferase bromodomain. Nature, 399, 491–496. Mellor, J. (2006) It takes a PHD to read the histone code. Cell, 126, 22–24. D. and Khorasanizadeh, S. (2003) Molecular basis for the discrimination of repressive methyl-lysine marks in histone H3 by Polycomb and HP1 chromodomains. Genes and Development, 17, 1870–1881. J. L. (2002) Function and selectivity of bromodomains in anchoring chromatin-modifying complexes to promoter nucleosomes.
Et al. (2007) The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA. Nature, 450, 908–912. , Nishidate, T. and Nakamura, Y. (2004) ICBP90, an E2F-1 target, recruits j17 j 1 New Frontiers in Epigenetic Modifications 18 13 14 15 16 17 18 19 20 21 22 HDAC1 and binds to methyl-CpG through its SRA domain. Oncogene, 23, 7601–7610. , Zhang, X. and Cheng, X. (2002) The PWWP domain of mammalian DNA methyltransferase Dnmt3b defines a new family of DNA-binding folds. Nature Structural Biology, 9, 217–224.
Epigenetic Targets in Drug Discovery, Volume 42 by Wolfgang Sippl, Manfred Jung, Raimund Mannhold, Hugo Kubinyi, Gerd Folkers
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