Forge uses the Cresset® patented ligand alignment algorithm to generate realistic, interpretable relationships between your molecules.

It includes an impressive range of SAR models that combine robust analysis with customizable parameters, ease of use and intuitive visualization. For SAR analysis, there is no need to look any further than Forge. Use it to:

• Build detailed pharmacophores

• Carry out detailed and accurate 3D ligand alignment

• Decipher complex SAR and communicate the results

• Design new molecules with the ideal activity and property profile.

Powerful SAR analysis andvisualization in Forge™Forge is a powerful ligand-focused workbench for understanding SAR and design

Cresset software models molecules in a way that is as close to high level quantum mechanics as possible, giving valuable insights into structure activity relationships.

Components of Forge

Evaluate Forge: cresset-group.com/forge

• Activity Atlas™

• Activity Miner™

• Ligand alignment

• 3D-QSAR

• FieldTemplater™

• Cresset Engine Broker™

Activity Atlas is a novel, qualitative method that generates three distinct maps of the electrostatic, shape and hydrophobic properties around your molecules. It can be used with small or large data sets and is particularly useful for projects where traditional 3D-QSAR approaches fail. Use Activity Atlas to:

• Understand your SAR data at a glance

• Condense large data tables into a single picture

• Know where to focus future optimization efforts

• Assess new molecules for novelty and their potential for activity.

Highlight your critical SAR regionsCreate a single picture of how changes in the electrostatic and shape properties of your molecules affect their activity. Activity Atlas uses activity cliff analysis to summarize the important changes in your dataset and highlight critical regions in your SAR.

Navigate complex SAR with Activity Atlas

Activity Atlas condenses your structure-activity data into highly visual 3D maps that inform the design and optimization of new compounds

Read more: cresset-group.com/activity-atlas

No strong SAR in this region

Small halogen preferred in the ortho position, shown by shape

and a negative electrostatic patternLarger substituents are

disfavored in this position

Strong signal that benzyl is favored here, shown by shape and electrostatic pattern

Electron-deficient aromatic ring favored here

Get a complete picture of your projectVisualize the electrostatic, hydrophobic and shape regions that you have already explored. Use this map to assess how much knowledge new designs will bring to your project and decide whether they are worth making.

Reveal your key features for activityMap the average electrostatic and shape patterns of your best molecules to determine the most important features for activity. These models are a simple and powerful way to guide new molecule design.

Most actives have a positive charge here

Most actives have H-bond acceptors here

This molecule lies outside the average shape of actives

Active molecules generally make hydrophobic interactions here

Highlight key activity changes in Activity Miner

Read more: cresset-group.com/activity-miner

Activity Miner gives you a clear rationale for changes in activity and selectivity and provides inspiration for how to exploit this knowledge in future design iterations. Use Activity Miner to:

• Rapidly navigate structure activity relationships, even on large datasets

• Focus on the SAR of a single molecule and see how simple changes impact activity and selectivity

• Understand the electrostatic and shape changes that cause differences in activity and selectivity

• See how new compounds relate to the entire history of the project, finding relationships that would otherwise be missed

• Develop critical insights into your SAR and use them to design new compounds.

Find and understand activity and selectivity cliffs in the SAR landscape

Compare the similarity between a chosen focus molecule and its closest neighbors using the innovative activity view. Easily assess the impact of small structural changes on activity and selectivity.

Get more insight with multiple views of your SAR

Pinpoint the most significant changes to your molecules using the sortable top pairs table. Find critical points in the SAR and understand how they relate to changes in physicochemical properties.

Get an insight into the chemical diversity of your dataset using cluster analysis based on 3D or 2D similarity. Visualize the spread of activities across clusters to identify homogenous subsets and important outliers.

Compare all your compounds at a glance with the disparity matrix. Color coding makes it easy to identify changes in activity and selectivity.

innovative science • intuitive software cresset-group.com

Build detailed pharmacophores with FieldTemplaterFieldTemplater helps you understand the electrostatic and shape characteristics of your molecules in the absence of protein X-ray data. Starting from 2D structures FieldTemplater provides you with hypotheses of their bioactive conformations and how they relate to each other.

These pharmacophores provide detailed information on the 3D relationships of known actives enabling the transfer of SAR from one series to another. They can form the basis for ligand alignment and QSAR experiments or be used to find new actives in virtual screening.

Speed up your experiments withCresset Engine BrokerThe Cresset Engine Broker lets you make maximum use of your computing resources by running calculations on remote servers to complete experiments in the shortest time possible.

Generate realistic ligand alignmentsForge generates realistic alignments of ligands with minimal manual intervention. Using our patented method you can align diverse or similar chemotypes based on their electrostatic and shape properties. This, combined with a sophisticated substructure based alignment algorithm, gives you the flexibility to generate informative relationships between your molecules.

Forge is available on Windows®, OS X® and Linux®. It can be accessed as an intuitive graphical user interface and as a series of task-focused

command line binaries. Forge capabilities can be accessed through KNIME® nodes and Pipeline Pilot™ components.

Create effective and informative 3D-QSAR modelsQSAR models in Forge decipher complex SAR and inform the design of new molecules. Quantitative and qualitative models can be generated using 2D and 3D descriptions of similarity.

Cresset’s field 3D-QSAR method is unique in using a small number of descriptors and adding gauge invariance which extends the utility of this popular method. Numerical and visual feedback on new molecule designs gives confidence that the next synthetic step will be the best possible choice.

Complementing this novel field QSAR method, Forge enables the building of k-Nearest Neighbor (k-NN) models based on either 2D or 3D electrostatic and shape similarity. This suite of QSAR techniques provides you with insights into your SAR and excellent predictivity in the design of new molecules.