title: A novel anabolic agent: a simvastatin analogue without HMG-CoA reductase inhibitory activity.
abstract: For the first time, structural information regarding the role of simvastatin in bone anabolism is described, and a bone-specific statin is introduced. Polyaspartate-conjugated simvastatin was synthesized by solid-phase synthesis with the assistance of microwave irradiation. It displays significant bone targeting and bone formation with less toxicity than simvastatin.
authors.affiliation: School of Pharmacy, ‡Department of Medicinal and Applied Chemistry, §Department of Fragrance and Cosmetic Science, ∥Orthopedic Research Center, ⊥Department of Physiology, and #Department of Orthopedics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University , Kaohsiung, Taiwan.
authors.forename: Kuang-Chan
authors.initials: KC
authors.lastname: Hsieh
authors.forename: Chai-Lin
authors.initials: CL
authors.lastname: Kao
authors.forename: Chien-Wei
authors.initials: CW
authors.lastname: Feng
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Wen
authors.forename: Hsin-Fang
authors.initials: HF
authors.lastname: Chang
authors.forename: Shu-Chun
authors.initials: SC
authors.lastname: Chuang
authors.forename: Gwo-Jaw
authors.initials: GJ
authors.lastname: Wang
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Ho
authors.forename: Shou-Mei
authors.initials: SM
authors.lastname: Wu
authors.forename: Je-Ken
authors.initials: JK
authors.lastname: Chang
authors.forename: Hui-Ting
authors.initials: HT
authors.lastname: Chen
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism*; D045930:Anabolic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D015394:Molecular Structure; D010012:Osteogenesis / Q000187:drug effects; D019821:Simvastatin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D060327:Solid-Phase Synthesis Techniques; D015027:Zebrafish
chemical_list: D000214:Acyl Coenzyme A; D045930:Anabolic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; D019821:Simvastatin