Medicine Design
We are interested in establishing alliances to develop and access novel:
Medicinal Chemistry Synthesis Technology
- Synthetic technologies that can accelerate the drug discovery process, including high-throughput chemistry, parallel medicinal chemistry, synthetic lab automation, biocatalysis, flow chemistry, photo- and electrochemistry
- Broadly applicable computational platforms to predict chemical reaction outcomes
- Synthetic methodologies for late-stage diversification
- Synthetic methodologies to access small, conformationally constrained multifunctional templates
- Novel monomers and building blocks in drug-like property space
Medicinal Chemistry
- Small molecule approaches to expand NCE target space – RNA splicing or translational modulation, non-CRBN and non-VHL mediated strategies for targeted protein degradation, heterobifunctional and/or molecular glue strategies to co-opt post-translational protein modification (i.e., ubiquitylation, deubiquitylation, phosphorylation) and/or induce protein mislocalization, 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
- Strategies to facilitate the conversion of Ab therapeutics to orally administered therapies
- New technologies to generate orally available peptides and peptidomimetics
- 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). Strategies to screen DEL libraries in cells and/or for membrane proteins.
- 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
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)
- 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
- Novel approaches and technology to achieving selective tissue distribution (including receptor mediated and transporter mediated strategies for therapeutic window enablement
- Determination of intracellular/sub-cellular unbound concentrations of transported drugs
- Transformative in vitro assays such as PK and PKPD on a chip
- Predictive in vitro or in silico absorption (fafg) models
- PBPK advances in clinical DDI prediction.