• Service Overview
• Gene–to-Structures
• Reagent Provision
• In Vitro Pharmacology
• Discovery Chemistry
• DMPK
• SBDD/FBDD
• In Vivo Models

Structural-based Drug Design (SBDD) / Fragment-based Drug Design (FBDD) is an alternative approach to drug discovery that starts from small molecule fragments and leads to novel hits and drug leads. The SBDD/FBDD approach typically involves testing fewer compounds, generating hits with wider scope for development (mw & Log P), and providing a complementary strategy to HTS.

Viva provides comprehensive SBDD/FBDD services to our clients. Our SBDD/FBDD team is headed by Dr. Shawn Cheng, Dr. Sean Ye, Dr. Derek Ren, and Dr. Cheney Mao. Dr. Shawn Cheng is an expert in affinity screening, compound library management and mass spectrometry with 13 years of experience as senior drug discovery scientist at Abbott Laboratories. Dr. Sean Ye is an expert in discovery chemistry with 14 years of drug discovery experience at Merck. Dr. Derek Ren is an expert in discovery biology with 10 years drug discovery experience at Pfizer. Dr. Cheney Mao is experienced in structure-based drug discovery in anti-HIV and anti-cancer area while working for 7 years at Hughes Institute.

We provide SBDD/FBDD services wtih a suite of technologies to address different needs of our clients. Viva's SBDD/FBDD platform is focused on X-ray crystallography, mass spectrometry binding analysis, NMR protein labeling methodology, as well as SPR, thermo-shift, and bioassay measurements.

Viva's SBDD/FBDD Approach:

   1.    First pass high throughout mass spec binding studies to identify winners
   2.    Compound prioritization according to affinity rank order and other information
   3.    X-ray, NMR and other methods to focus on high priority compounds
   4.    Rapid hit-to-lead and lead optimization with structure-guided synthesis
 

Technology Description:

X-ray Crystallography Based

Single or small mixtures of compounds with soaking-in or co-crystallization

Features

Detailed information about protein structure, ligand binding site and binding mode       Can detect weak ligands

Requires protein crystallization

Relative low throughput and requires high compound concentration (solubility)       Ligand co-crystallization and ligand affinity may not correlate     Timeline       Preparation for crystallizable protein: 1-3 months       Crystallization trial and structure determination       Soaking and co-crystallization: several weeks

Mass Spectrometry Based Identifies non-covalent protein-ligand interactions

Affinity Selection Mass Spectrometry (ASMS) Iterative affinity selection under equilibrium conditions with LCMS analysis. Rank order affinity for compound mixtures, Kd for single compounds

Features

Generally applicable to any soluble proteins and compound library mixtures.       Equilibrium solution binding, low uM compound concentration       Label free, no need to immobilize protein, requires no assay development.       Variable ligand affinity detectable depends on protein concentration       Can be very high throughput

Need soluble proteins       Compounds need to be reasonably LCMS sensitive       Need additional experiments for binding mechanism and binding site information      Timeline       A few days to rank order affinity for small number of compounds       2-4 weeks for large number of compounds (100 to >1000)