title: 3D-QSAR and docking studies on transforming growth factor (TGF)-beta receptor 1 antagonists.
abstract: The transforming growth factor-beta (TGF-beta) is part of a family of cytokines which regulate various signaling pathways such as cell development, growth, and tissue injury. Although several studies have been published describing the synthesis of small compounds which inhibit the receptor of TGF-beta, especially the subtype 1 receptor (TGBR1) kinase, no 3D-quantitiative structure-activity relationship study has been published. Here we describe the development of a comparative molecular field analysis (CoMFA) model which yielded a partial least squares statistical cross validated r(2) of >0.3. CoMFA maps agree with docking studies and pharmacophore analysis that hydrogen bonding is important for binding to ALK-5. These studies could enable the medicinal chemist to develop novel inhibitors which can be used in glaucoma filtration surgery.
authors.affiliation: Department of Pharmaceutical Sciences, Northeastern Ohio Universities Colleges of Medicine and Pharmacy, Rootstown, OH, USA. wgeldenh@neoucom.edu
authors.forename: Werner J
authors.initials: WJ
authors.lastname: Geldenhuys
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakamura
mesh_terms: D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors*
chemical_list: D018125:Receptors, Transforming Growth Factor beta