3D-QSAR and docking studies on transforming growth factor (TGF)-β receptor 1 antagonists

The transforming growth factor-β (TGF-β) 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-β, 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 r2 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.

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