title: [The design of muti-target antitumor drugs affecting on FTase and Raf-1 kinase].
abstract: Ras/Raf/MEK/ERK singal transduction plays an important role in cell proliferation, differentiation, apoptosis, metastasis and metabolism. This investigation focused on this signal pathway and chose farnesyl transferase (FTase) as the main target and Raf-1 kinase as the second target. A lot of compounds were selected to construct the pharmacophore models of farnesyl transferase inhibitors (FTIs) and Raf-1 kinase inhibitors by using computer-aided drug design (CADD). The pharmacophore of FTIs is constituted by a hydrogen bonding acceptor, an aromatic ring, a positive ionizable and two hydrophobic regions; the pharmacophore of Raf-1 kinase is constituted by a hydrogen donor, a hydrogen acceptor, a hydrophobic regions and an aromatic ring. There are some similarities between the two pharmacophores. After analysis of the constructions of these two pharmacophores, some new aminomethylbenzoic acid derivatives with good forecasting activity against both of FTase and Raf-1 kinase were designed with these new pharmacophore models.
authors.affiliation: School of Pharmacy, Tong]i Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhao
authors.forename: Yi-jing
authors.initials: YJ
authors.lastname: Zhu
authors.forename: Lu
authors.initials: L
authors.lastname: Zeng
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Feng-chao
authors.initials: FC
authors.lastname: Jiang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017076:Computer-Aided Design; D016503:Drug Delivery Systems; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D019908:Proto-Oncogene Proteins c-raf / Q000037:antagonists & inhibitors*; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D051231:Farnesyltranstransferase; D019908:Proto-Oncogene Proteins c-raf