GS-9620 is a potent and selective agonist of toll-like receptor 7 (TLR7), currently in clinical evaluation for the treatment of chronic Hepatitis B (HBV) infection. This pteridinone-based compound was identified and optimized in the absence of a structural model using a ligand-based design approach. Since its discovery however, a structure for the active form of the closely related toll-like receptor 8 (TLR8) has been solved. Constructing a homology model, we report a retrospective structure-based analysis of the SAR around GS-9620, laying the foundation for further discovery of TLR agonists.Model of GS-9620 in the active form of TLR7.

Identification and optimization of toll-like receptor 7 agonists: A retrospective structure-based analysis

248th National Meeting (2014)

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