- Rational Design and Synthesis of Selective PRMT4 Inhibitors: A New Chemotype for Development of Cancer Therapeutics**
-
Protein arginine N-methyl transferase 4 (PRMT4) asymmetrically dimethylates the arginine residues of histone H3 and nonhistone proteins. The overexpression of PRMT4 in several cancers has stimulated interest in the discovery of inhibitors as biological tools and, potentially, therapeutics. Although several PRMT4 inhibitors have been reported, most display poor selectivity against other members of the PRMT family of methyl transferases. Herein, we report the structure-based design of a new class of alanine-containing 3-arylindoles as potent and selective PRMT4 inhibitors, and describe key structure–activity relationships for this class of compounds.
- Sutherland, Mathew,Li, Alice,Kaghad, Anissa,Panagopoulos, Dimitrios,Li, Fengling,Szewczyk, Magdalena,Smil, David,Scholten, Cora,Bouché, Léa,Stellfeld, Timo,Arrowsmith, Cheryl H.,Barsyte, Dalia,Vedadi, Masoud,Hartung, Ingo V.,Steuber, Holger,Britton, Robert,Santhakumar, Vijayaratnam
-
supporting information
p. 1116 - 1125
(2021/03/08)
-
- FUSED PYRAZINE DERIVATIVES AS KINASE INHIBITORS
-
A series of quinoxaline derivatives, and analogues thereof, which are functionalised further by a substituted phenyl or pyridinyl moiety, being selective inhibitors of PO kinase enzymes, are accordingly of benefit in medicine, for example in the treatment of inflammatory, autoimmune, cardiovascular, neurodegenerative, metabolic, oncological, nociceptive or ophthalmic conditions.
- -
-
Page/Page column 56-57
(2010/06/11)
-
- Synthesis and PKCθ inhibitory activity of a series of 5-vinyl phenyl sulfonamide-3-pyridinecarbonitriles
-
A series of 5-vinyl phenyl sulfonamide-3-pyridinecarbonitriles were prepared and evaluated as PKCθ inhibitors. Optimization resulted in the identification of compound 15 with an IC50 value 0.44 nM for the inhibition of PKCθ with 150-fold select
- Shim, Jaechul,Eid, Clark,Lee, Julie,Liu, Erica,Chaudhary, Divya,Boschelli, Diane H.
-
scheme or table
p. 6575 - 6577
(2010/06/12)
-
