Virtual screening and biological characterization of novel histone arginine methyltransferase PRMT1 inhibitors was written by Heinke, Ralf;Spannhoff, Astrid;Meier, Rene;Trojer, Patrick;Bauer, Ingo;Jung, Manfred;Sippl, Wolfgang. And the article was included in ChemMedChem in 2009.Reference of 129-74-8 This article mentions the following:
Lysine and arginine methyltransferases participate in the posttranslational modification of histones and regulate key cellular functions. Protein arginine methyltransferase 1 (PRMT1) has been identified as an essential component of mixed lineage leukemia (MLL) oncogenic complexes, revealing its potential as a novel therapeutic target in human cancer. The first potent arginine methyltransferase inhibitors were recently discovered by random- and target-based screening approaches. Herein we report virtual and biol. screening for novel inhibitors of PRMT1. Structure-based virtual screening (VS) of the Chembridge database composed of 328 000 mols. was performed with a combination of ligand- and target-based in silico approaches. Nine inhibitors were identified from the top-scored docking solutions; these were exptl. tested using human PRMT1 and an antibody-based assay with a time-resolved fluorescence readout. Among several aromatic amines, an aliphatic amine and an amide were also found to be active in the micromolar range. In the experiment, the researchers used many compounds, for example, 1-(4-(tert-Butyl)benzyl)-4-((4-chlorophenyl)(phenyl)methyl)piperazine dihydrochloride (cas: 129-74-8Reference of 129-74-8).
1-(4-(tert-Butyl)benzyl)-4-((4-chlorophenyl)(phenyl)methyl)piperazine dihydrochloride (cas: 129-74-8) belongs to piperazine derivatives. A form in which piperazine is commonly available industrially is as the hexahydrate, C4H10N2. 6H2O, which melts at 44 掳C and boils at 125鈥?30 掳C. Piperazine and its salts did not induce point mutations in a bacterial test. A series of mutagenicity studies in cells, both in vitro and in vivo, has been completed and showed no evidence of mutagenic effect.Reference of 129-74-8
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics