Medicine Design

We are interested in establishing alliances to develop and access novel:

Medicinal Chemistry Synthesis Technology

• Synthetic technologies that can accelerate the delivery of API
• Flow chemistry approaches that enable mg to kg scale
• Efficient scale-up (kg) capabilities for photo redox chemistry
• Chemical transformations via biocatalysis
• Synthetic methodologies for late-stage diversification
• Synthetic methodology to access small conformationally constrained multifunctional templates
• Monomers and building blocks in drug-like property space
• High-throughput optimization capabilities for synthetic transformations and biocatalysis
• Innovative capabilities for parallel medicinal chemistry

Medicinal Chemistry

• Small molecule approaches to expand NCE target space – RNA splicing or translational modulation, orally bioavailable or CNS-penetrant protein degradation, non-CRBN and non-VHL mediated strategies for targeted protein degradation, protein stabilization via recruitment of deubiquitinases (i.e., DUBTACs), covalent inhibition, modulation of protein-protein interactions and non-Ro5 compounds
• Solute ligand carrier, transcription factor, deubiquitylating (DUB) enzyme, phosphatase, RNA binding protein, and biomolecular condensate modulator design and screening technologies
• AI/ML methodologies to predict novel protein or RNA structures and their complexes with small molecules or other biomolecules
• Membrane protein structural biology technologies and capabilities, including ion channels, GPCRs and solute carrier proteins
• DNA-compatible synthetic protocols and DNA backbone modifications that expand currently available methodology for DNA-encoded libraries (DEL)
• Computational methods for quantitative affinity prediction and molecular dynamics simulation
• Technologies to identify hits through virtual screening of very large compound collections
• Ligand-based multi-parametric generative design platforms
• Systems/chemical biology technologies enabling mechanism determination for phenotypic screening hits
• Morphological or transcriptional profiling technologies to enable hit expansion and pathway inferences for phenotypic screening
• Functional genomic and iPSC technology to enable facile generation of disease relevant cell systems for phenotypic screening

Pharmacokinetics Dynamics and Metabolism (PDM)

• Translation
  • Translational modeling and simulation approaches, systems pharmacology/PK-PD; deep knowledge of targets/pathways; increased confidence in target drug selection
• Bioanalysis and biomarkers
  • Novel bioanalytical and cellular imaging techniques
  • Specific biomarkers of ADME DDI liability (both transporter and enzyme biomarkers)
  • Novel methodology for pull-down of tissue specific exosomes
• Disposition and delivery of therapies
  • Novel commercially viable delivery technologies (oral and non-oral, including topical)
  • Biodistribution of nanoparticles at whole organ and cellular level
• Targeting, prediction and modeling of transporter-mediated disposition and DDIs – small molecules
  • Quantitation and scaling of transporters for input into physiological PK models of tissue penetration and clearance including biliary clearance
  • Determination of intracellular/sub-cellular unbound concentrations of transported drugs
• Novel approaches to achieving selective tissue distribution (including receptor mediated and transporter mediated strategies)
• Transformative in vitro assays such as PK and PKPD on a chip
• Technologies that enable tissue specificity and therapeutic window enablement
• PBPK to predict clinical DDI