Current Focus: GPCRs
GPCRs are key to human health.
G-protein coupled receptors (GPCRs) form the largest human membrane protein family with 826 identified members. Their function spans nearly all physiological functions, including metabolism, immune system regulation, heart rate, behavior and sensory system, meaning they are important therapeutic targets. To date, there are approximately 475 drugs on the market acting at over 100 unique GPCRs. Yet, more than 220 GPCRs have not yet been explored as clinical targets, representing broad untapped therapeutic potential.
GPCRs are inherently challenging targets
GPCRs are mechanistically complex. Their primary function is to recognize extracellular substances (primarily ligands) and transmit signals across the cell membrane to the inside of the cell. Extracellular ligands bind to GPCRs to induce conformational changes, which impact downstream signaling. Ligand binding can result in various activation patterns of downstream pathways including G-proteins, β-arrestins and other non-G-protein transducers, leading to both physiologic and pathologic effects.
GPCR structural visualization is complex, making GPCR structure-based drug discovery challenging.
Low and unstable GPCR protein expression can create significant hurdles to structural and pharmacological characterization.
Diversity in downstream signaling pathways can lead to off-target effects by activating unintended pathways.
Similarity among GPCR binding sites hinder efforts to design drugs with specific receptor selectivity.
The Structure solution
With an unparalleled track record in GPCR structure-based drug design, Structure’s team expertly deploys breakthrough technical advances to navigate these challenges in pursuit of innovative small molecule drugs. Our team has extensive experience with these notoriously difficult targets, including our founders who solved the first human GPCR crystal structure bound to a diffusible ligand.
Structure’s platform unlocks the potential of GPCRs.
Our platform integrates multiple groundbreaking technologies designed to overcome the historical limitations of GPCR drug development.
Insights into protein structure and dynamics drive intelligent drug design.
Our structure-based technology platform combines direct visualization of receptor-binding interactions with advanced simulation of molecular motion and signal transduction. This allows us to design molecules with ideal binding properties and confirmational characteristics to elicit precise downstream signaling.
Cutting-edge computational chemistry powered by Schrodinger
Structural techniques, including cryo-EM and X-ray crystallography
State-of-the-art small molecule hit identification including DNA encoded library (DEL) technology and affinity mass spectrometry selections
Medicinal chemistry along with a matrix of pharmacological assay platform
Built for speed and efficiency.
Basecamp Bio, our wholly owned subsidiary, focuses on early discovery and technology development. Basecamp Bio optimizes proprietary in-house drug discovery tools to enable the synthesis and screening of vast numbers of small molecule product candidates at a scale that is not possible to achieve with traditional methods.
We take an iterative computational approach to evaluate and optimize molecules in silico ahead of synthesis and assay. This can accelerate the lead optimization process, reduce development cost and potentially increase likelihood of clinical success compared to traditional drug discovery.
Our ultimate goal:
Innovative small molecules.
Our expertise in structure-based drug design results in small molecules with enhanced activity, tailor-made signaling response and improved selectivity while maintaining ideal pharmaceutical properties. We aim to create small molecules with biologic-like activity and specificity without the inherent limitations of biologics.
Drug Discovery Partnering
Our drug discovery engine enables rapid and efficient progress to clinic-ready assets. We will explore selective partnerships to tackle challenging cell receptor targets pursued by the biopharmaceutical industry. Interested in partnering with us? Contact us today.
Why small molecules now?
With recent advances in structure-based drug discovery approaches, we can now design tailor made medicines to elicit precise downstream signaling effects to ameliorate disease. These oral small molecule drugs can now offer improved patient experience and broad access coupled with the therapeutic activity of biologics.
Presentations & Publications
Explore over two decades of publications that are the foundation of Structure’s innovative technology and approach.