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Rational Design and Synthesis of Selective PRMT4 Inhibitors: A New Chemotype for Development of Cancer Therapeutics*.
- Source :
-
ChemMedChem [ChemMedChem] 2021 Apr 08; Vol. 16 (7), pp. 1116-1125. Date of Electronic Publication: 2021 Mar 04. - Publication Year :
- 2021
-
Abstract
- 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.<br /> (© 2021 Wiley-VCH GmbH.)
- Subjects :
- Alanine chemistry
Antineoplastic Agents chemical synthesis
Antineoplastic Agents chemistry
Dose-Response Relationship, Drug
Enzyme Inhibitors chemical synthesis
Enzyme Inhibitors chemistry
HEK293 Cells
Humans
Indoles chemical synthesis
Indoles chemistry
Molecular Structure
Neoplasms metabolism
Protein-Arginine N-Methyltransferases genetics
Protein-Arginine N-Methyltransferases metabolism
Structure-Activity Relationship
Alanine pharmacology
Antineoplastic Agents pharmacology
Drug Design
Enzyme Inhibitors pharmacology
Indoles pharmacology
Neoplasms drug therapy
Protein-Arginine N-Methyltransferases antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1860-7187
- Volume :
- 16
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- ChemMedChem
- Publication Type :
- Academic Journal
- Accession number :
- 33513288
- Full Text :
- https://doi.org/10.1002/cmdc.202100018