title: In silico design and synthesis of piperazine-1-pyrrolidine-2,5-dione scaffold-based novel malic enzyme inhibitors.
abstract: Fragment-based virtual library design and virtual screening have been conducted against malic enzyme (ME) homology model. Several scaffolds have been identified as promising motifs to target ME's NADP binding site. One small focused library has been synthesized and tested against ME. Several compounds from this library have shown sub-micromolar inhibitory activity against malic enzyme.
authors.affiliation: Cytrx Laboratories, One Innovation Drive, Worcester, MA 01605, USA. jzhang@cytrx.com
authors.forename: Y John
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Zhaolin
authors.initials: Z
authors.lastname: Wang
authors.forename: Dennis
authors.initials: D
authors.lastname: Sprous
authors.forename: Roustem
authors.initials: R
authors.lastname: Nabioullin
mesh_terms: D001665:Binding Sites; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D003600:Cytosol / Q000201:enzymology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D008291:Malate Dehydrogenase / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D000077489:Piperazine; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011487:Protein Conformation; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000494:pharmacology; D011760:Pyrrolidinones / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D010879:Piperazines; D011759:Pyrrolidines; D011760:Pyrrolidinones; C508940:piperazine-1-pyrrolidine-2,5-dione; D000077489:Piperazine; D009249:NADP; D008291:Malate Dehydrogenase