Structure-based design platform for sodium channel-targeting insecticides

Overview

This offering provides a structure-based insecticide development platform focused on voltage-gated sodium (Nav) channels and other major insecticide targets. The platform combines cryo-EM structural determination with biophysical screening, electrophysiology, molecular docking, machine learning, directed evolution, and synthetic biology to design and optimize insecticidal molecules. It addresses both wild-type and resistant pest populations across Lepidoptera, hoppers, and thrips, and extends to additional targets such as ryanodine receptor, GABA receptor, and acetyl-CoA carboxylase.

Technical specifications

• Cryo-EM structure determination of insect Nav channels and other targets in complex with insecticidal molecules
• Surface plasmon resonance (SPR) binding assays for compound characterization
• Electrophysiology to evaluate functional modulation of channel gating
• Molecular docking for computational compound fitting and optimization
• Fluorescence-based high-throughput screening (HTS) developed in-house against wild-type and resistant ion channel targets
• Machine learning and directed evolution to guide compound improvement
• Synthetic biology workflows for recombinant expression of insect sodium channels
• Demonstrated potency increases of more than 1000-fold for existing insecticidal molecules
• Capability to elucidate molecular mechanisms of insecticide resistance and design anti-resistance compounds

Technology readiness level

The platform has produced multiple Nav-insecticide complex structures and validated compounds with greater than 1000-fold potency improvements against agricultural pests. Future validation includes solving cryo-EM structures of partner-supplied candidate compounds (approximately 6-12 months per structure), performing structure-based computational design and optimization (approximately 6-12 months), and screening partner libraries via in-house fluorescence-based HTS. The team is also open to co-development and commercialization of existing insecticidal molecules.