title: Diphenyl urea derivatives as inhibitors of transketolase: a structure-based virtual screening.
abstract: Transketolase is an enzyme involved in a critical step of the non-oxidative branch of the pentose phosphate pathway whose inhibition could lead to new anticancer drugs. Here, we report new human transketolase inhibitors, based on the phenyl urea scaffold, found by applying structure-based virtual screening. These inhibitors are designed to cover a hot spot in the dimerization interface of the homodimer of the enzyme, providing for the first time compounds with a suggested novel binding mode not based on mimicking the thiamine pyrophosphate cofactor.
authors.affiliation: Departamento de Química Física, Facultat de Química, Universitat de Barcelona and Institut de Recerca en Química Teòrica i Computacional, Barcelona, Spain.
authors.forename: Cristian
authors.initials: C
authors.lastname: Obiol-Pardo
authors.forename: Gema
authors.initials: G
authors.lastname: Alcarraz-Vizán
authors.forename: Marta
authors.initials: M
authors.lastname: Cascante
authors.forename: Jaime
authors.initials: J
authors.lastname: Rubio-Martinez
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002224:Carbanilides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D014174:Transketolase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D014584:User-Computer Interface
chemical_list: D000970:Antineoplastic Agents; D002224:Carbanilides; D004791:Enzyme Inhibitors; D014174:Transketolase