Medicinal & Computational Chemistry

Cayman’s medicinal and computational chemistry services, supported by structure-based drug design (SBDD) and computer-aided drug design (CADD), offer a fully integrated, multidisciplinary approach to developing a wide range of therapeutics. Our scientists have the expertise and technology to bring your drug discovery program through preclinical stages of development. Whether it’s hit identification, lead generation or optimization, route and methods development, screening, or scale-up, Cayman’s experienced medicinal chemists, structural biologists, and biochemists possess the skills to accelerate your preclinical drug discovery programs.

Hit Identification

Virtual High-Throughput Screening (vHTS)

Cayman offers vHTS services backed by expertise in medicinal chemistry, structural biology, and Schrödinger suite, a computational platform used to accelerate drug discovery. Our scientists can virtually screen more than 12 million compounds for hit identification, including fragments, drug-like, near drug-like, and lead-like compounds from the Enamine^® Stock Screening Compounds Collection and the MilliporeSigma Aldrich Market Select^® Screening Collection Phase databases, which are updated quarterly. Glide docking, shape screening, and pharmacophore-based ligand screening are also available in addition to vHTS. We work with you to identify and source top-ranked compounds for further screening.

Stock Screening Compounds Collection (Enamine^® )

Aldrich Market Select^® (MilliporeSigma)

SARS-CoV-2 Screening Library Data Package

We also offer a SARS-CoV-2 Screening Library Data Package consisting of 2,000+ FDA-approved and drug-like compounds identified from in silico modeling using Maestro (Schrödinger Suite) software. This data package includes compound characteristics, docking scores (per target), and predicted physicochemical properties for ten SARS-CoV-2 targets, including the spike glycoprotein, proteases, and non-structural proteins (nsps), and human angiotensin-converting enzyme 2 (ACE2).

MM-GBSA & FEP

Molecular mechanics generalized Born surface area (MM-GBSA) analysis can be used to calculate ligand binding energies, which are approximate free energies of ligand binding, and ligand strain energies for a set of ligands and a single receptor to obtain more enrichment. We can also perform free energy perturbation (FEP) analysis to compute binding free energies and provide a complete description of the binding event with highly accurate predictions and better enrichment using a thermodynamically rigorous approach.

Hit-to-Lead Optimization

Custom Synthesis & Parallel Library Generation

Our medicinal chemists perform iterative library design and synthesis using parallel medicinal chemistry. Virtual library enumeration with predicted in silico property calculations facilitates the generation of small, focused libraries (20-100 compounds) to quickly learn the SAR around lead templates.

SAR & Lead Optimization

Identify, prioritize, and optimize lead candidates leveraging our expertise in SBDD, organic synthesis, and activity screening. Identify key interactions, model pharmacophores, enumerate hits, and predict binding, physicochemical, and ADME/tox properties.

Biophysical Characterization

We offer a variety of biophysical methods, including surface plasmon resonance (SPR), thermal shift assay (TSA), and dynamic light scattering (DLS), to help you characterize small molecules and proteins, understand molecular interactions and binding mechanisms, and optimize drug-target interactions.

Process Scaling

Route Optimization & Scale-Up

Employing process design strategies, our chemists explore synthetic routes and solvent optimization ensuring scalability up to 0.5 kg.

Pre-GMP Process Development

We offer method development and manufacturing-scale process validation to vet starting materials, ensure optimal yield, identify impurities, and explore the necessity and feasibility of alternative routes. Consult with our experienced API manufacturing team to ensure your compound is scalable in a GMP manufacturing environment.

Pricing

For more information about our Medicinal Chemistry & Structural Biology services and project-specific pricing, please submit the “Contact Us” form.

Related Services

Target Validation

Our biomarker development group performs screening and profiling for drug discovery and diagnostics using multiple platforms. We offer scalable assays (catalog or custom) for single- or multi-analyte studies with automation capabilities.

Activity screening can be performed using your compounds in biochemical or functional assays. Leverage our expertise to custom build a screening assay on a variety of enzyme activity and cell-based platforms or choose from our extensive catalog of assays.

Hit Identification

Our high-throughput screening services offer fully automated compound screening for hit identification and lead discovery, validation of hits from vHTS, SAR studies, and hit-to-lead optimization.

DMPK & Drug Safety Profiling

We offer mass spectrometry-based analytical services for the detection and quantification of drugs, metabolites, and biomarkers in biological samples to support pharmacokinetics studies. Our team of experts can help develop fit-for-purpose methods for discovery, pharmacokinetics, and formulation applications to support your drug discovery efforts.

Cayman’s experts can perform mitochondrial toxicity screening and metabolic and functional analysis of mitochondria or whole cells to assess the effects of lead compounds on cell health and metabolism. These studies are compatible with primary cells and established cell lines, as well as custom cellular models of disease generated by our scientists.

View the Posters

• Fragment-Based Drug Discovery (FBDD) Approach for TNF-α
• Discovery of Novel Heterocycle Inhibitors: Hit to Lead Compound in <10 Months
• Selection and Characterization of hSTING-Agonists via In Silico Modeling and SPR
• Novel Experimental Therapeutics for COVID-19 Derived From a Nitric Oxide Dono
• Study of Novel Aspartate Aminotransferase Inhibitor Binding Mechanism Through Structure-Based Mutational Analysis

Cayman Collaborations & Co-Authored Publications

• Novel Amide and Imidazole Compounds as Potent Hematopoietic Prostaglandin D₂ Synthase Inhibitors