- The discovery of SKLB-0335 as a paralog-selective EZH2 covalent inhibitor
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By targeting the unique Cys663 of EZH2, SKLB-0335 displays high paralog-selectivity on EZH2. Biochemical studies show that SKLB-0335 can covalently bind to EZH2 at its S-adenosylmethionine (SAM) pocket and inhibit H3K27Me3. SKLB-0335 could be an effective chemical probe with which to further investigate the specific biological functions of EZH2.
- Zhang, Qiangsheng,Hu, Xi,Li, Lu,Zhang, Lidan,Wan, Guoquan,Feng, Qiang,Zhu, Yongxia,Wang, Ningyu,Liu, Zhihao,Yu, Luoting
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supporting information
p. 3006 - 3009
(2021/03/29)
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- Amination/Cyclization Cascade by Acid-Catalyzed Activation of Indolenine for the One-Pot Synthesis of Phaitanthrin E
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We have developed a concise one-pot synthesis of phaitanthrin E derivatives, where simple starting materials undergo an acid-catalyzed intermolecular amination/intramolecular cyclization cascade.
- Abe, Takumi,Yamada, Koji
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p. 6504 - 6507
(2016/12/23)
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- Identification of small-molecule enhancers of arginine methylation catalyzed by coactivator-associated arginine methyltransferase 1
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Arginine methylation is a common post-translational modification that is crucial in modulating gene expression at multiple critical levels. The arginine methyltransferases (PRMTs) are envisaged as promising druggable targets, but their role in physiological and pathological pathways is far from being clear due to the limited number of modulators reported to date. In this effort, enzyme activators can be invaluable tools useful as gain-of-function reagents to interrogate the biological roles in cells and in vivo of PRMTs. Yet the identification of such molecules is rarely pursued. Herein we describe a series of aryl ureido acetamido indole carboxylates (dubbed "uracandolates"), able to increase the methylation of histone (H3) or nonhistone (polyadenylate-binding protein 1, PABP1) substrates induced by coactivator-associated arginine methyltransferase 1 (CARM1), both in in vitro and cellular settings. To the best of our knowledge, this is the first report of compounds acting as CARM1 activators.
- Castellano, Sabrina,Spannhoff, Astrid,Milite, Ciro,Dal Piaz, Fabrizio,Cheng, Donghang,Tosco, Alessandra,Viviano, Monica,Yamani, Abdellah,Cianciulli, Agostino,Sala, Marina,Cura, Vincent,Cavarelli, Jean,Novellino, Ettore,Mai, Antonello,Bedford, Mark T.,Sbardella, Gianluca
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p. 9875 - 9890
(2013/01/16)
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- NEW SUBSTITUTED ARYLSULPHONYLGLYCINES, THE PREPARATION THEREOF AND THE USE THEREOF AS PHARMACEUTICAL COMPOSITIONS
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The present invention relates to substituted arylsulphonylglycines of general formula (I) wherein R, X, Y and Z are defined as in claim 1, the tautomers, enantiomers, diastereomers, mixtures thereof and salts thereof, which have valuable pharmacological properties, particularly the suppression of the interaction of glycogen phosphorylase a with the GL subunit of glycogen-associated protein phosphatase 1 (PP1 ), and their use as pharmaceutical compositions.
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Page/Page column 124
(2008/12/07)
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- ANTIPARASITIC COMPOUNDS AND COMPOSITIONS
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Disclosed is use of a compound having a structure according to general formula (I) defined below, in the manufacture of a medicament to treat and/or prevent a parasitic infection or infestation in a mammalian subject wherein X1 = N or CH or C=O (X2 = NH) or C=S (X2 = NH) or C-OR1 or C-halogen or C-azide; X2 = N or CR1 or C-halogen or CS(O)nR1 where n = 0-2 or a (C)m linker where m = 1-3 between X2 and X6 or C-X5X6 (in which case X5X6 at C6 (purine numbering) is replaced by H or NHR1 or O or OR1 or S or SR1); X3 = N or CH or C-NO2; X4 = N or CH or C-NO2 or C-NR1R2 or an amidine derivative or a guanidinium derivative; X5 = O or NR1 or CR1R2; X6 = OR1 or O-acyl or 0-S(O)nR1 or NR1R2 or NH-acyl or N(Acyl)2 or NH-OS(O)2R1 or NH-S(O)nR1 where n = 0-2 or a hydrazone derivative or an oxime derivative, but if X5 = O, X6 cannot = O or X5X6 is an amidine or an N-substituted pyridine or substituted guanidine; Y = H or NH2 or NR1R2 or -O (X3 = NH) or OR1 or F or Cl or Br or I or CR1R2R3 or S(O)nR1 where n = 0-2 or azide or X5X6 (in which case X5X6 at C6 (purine numbering) is replaced by H or NHR1 or O or OR1 or S or SR1); R1, R2, R3 are independently selected from the group consisting of H or (optionally substituted), alkyl, alkenyl or alkynyl or aryl or aralkyl where the substituents may be selected from H, OH, NH2, halogen, N3, CN, CHO, COOR', C0NR'2, OR, NE'2, SR', NR'NR'2, NR'OR', NO2 and R' is alkyl, alkenyl, alkynyl, aralkyl, acyl, sulfonyl; Z = H or substituted (alkyl or alkenyl or alkynyl or aralkyl) or a sugar derivative of general formula (II) in the β-configuration where: B is the nucleobase from Formula (I); X7 = CH2 or O or NR1 or S; R4 = H or OH or OR1 or halogen or azide or a phosphate derivative; R5 = H or F or CH3; R6 = H or OH or OR1 or halogen or azide or a phosphate derivative; and R7 = H or halogen or R1 or a derivative of an amino acid or PO3H2 or P2O6H3 or P3O9H4 or a methylene derivative of P2O6H3 or P3O9H4 or a masked phosphate or a phosphonate derivative (5'-O replaced with CH2).
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- Effect of a hydrogen bonding carboxamide group on universal bases
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A number of aromatic universal base analogues have been described in the literature, but most are non-hydrogen bonding. We have examined the effect of introducing hydrogen bonding carboxamide groups onto the pyrrole ring of 5-nitroindole. The modified ana
- Too, Kathleen,Brown, Daniel M.,Holliger, Philipp,Loakes, David
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p. 899 - 911
(2008/02/03)
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