SYBYL-X:  Lead Optimization

In lead optimization, a factor of ten in the potency of a drug candidate can make the difference between a successful candidate and project failure. SYBYL-X's QSAR and 3D QSAR capabilities allow researchers in Lead Optimization projects to go beyond categorizing structures as active or inactive and allow them to predict the level of biological activity or potency based on structure-activity data.

In addition, a successful drug candidate will need to overcome a variety of hurdles, including potency and selectivity, and have acceptable ADME, physical and safety properties. SYBYL-X allows researchers to develop ligand-based and/or structure-based models that address the multiple criteria that must be considered in lead optimization. Recent advances in SYBYL-X’s 3D QSAR capabilities make modeling multiple biological endpoints quick and easy. Now, 3D QSAR models can be created in minutes, instead of weeks.

Structure-based design capabilities in SYBYL-X allow researchers to understand and rationalize drug interactions with its receptor, to identify potential new binding interactions that will provide ‘step jumps’ in potency, or to identify options for improving ADME or physical properties without disrupting key receptor interactions. With SYBYL-X’s Surflex-Dock, scientists can use SAR information to improve scoring and customize scoring for the target of interest.

When a structure of the drug’s target isn’t known, SYBYL-X’s pharmacophore hypothesis generation and molecular alignment tools allow researchers to deduce spatial requirements for drug binding and test new ideas to see how they match to a set of lead drug candidates.

Using SYBYL-X, you can:

• Perform critical ligand-based design tasks, like structure-activity relationship modeling, pharmacophore hypothesis generation, molecular alignment, and ADME prediction
• Identify new R-groups that are predicted to improve potency or have desirable ADME properties using R-Group Virtual Screening
• When a structure of the drug’s target isn’t known, SYBYL-X’s pharmacophore hypothesis generation and molecular alignment tools allow researchers to deduce spatial requirements for drug binding and test new ideas to see how they match to a set of lead drug candidates
• Use protein-ligand docking to understand and rationalize potential drug interactions with its receptor, identify potential new binding interactions that will provide ‘step jumps’ in potency, or identify options for improving ADME or physical properties without disrupting key receptor interactions using SYBYL-X’s docking capabilities
• Accurately predict relevant pharmacological, ADME, or physical properties based on available SAR data
• Visualize Structure-Activity trends and identify regions for fruitful structural variation

SYBYL-X Core Technologies: QSAR with CoMFA, HQSAR, Surflex-Dock, CScore, Topomer Search, Topomer CoMFA, Discotech, Surflex-Sim

Recommended à la carte add ons: Volsurf+