software
Spark™ for scaffold hopping and bioisosteric replacement
Generate highly innovative ideas for your project to explore chemical space and escape IP and toxicity traps
Ignite your chemical creativity
Commonly recognized by our customers to be the best scaffold hopping and bioisosteric replacement tool on the market, Spark helps chemists to fuel their early-stage projects with more ideas, prioritizing compounds that can be made most easily in the lab. By mimicking the electrostatics and shape of a chosen starting ligand, ranked results will include expected, unexpected, and completely novel structures.
Find the freedom to operate even in congested IP spaces, avoiding patent-related issues, through the replacement of known scaffolds with novel bioisosteric replacements. Expand your own IP, by fully enumerating different regions of an existing active molecule.
Reduce the risk of late-stage attrition by replacing a functional group that is important for binding, but metabolically problematic. Spark’s multi-parametric optimization allows users to quickly select compounds based on their bioisosteric ‘fit’ and other properties including LogP (for optimal absorption), TPSA (for cell permeability), and molecular weight. Through this, molecules can be optimized to minimize side effects, gain optimal pharmacokinetic properties, and achieve metabolic stability.
- Generate highly innovative ideas for your project
- Escape and expand chemical IP
- Reduce the risk of late-stage attrition
- Find the best R-groups from your reagents
- Grow a ligand into new space in your protein active site
- Join two ligands sitting in different regions of your protein active site
- Cyclize a molecule by joining two atoms with a linker
- Search for an R-group to displace a crystallographic water molecule near your ligand
- Prioritize the compounds that can be made easily in the lab
Spark fragment databases
Spark fragment databases are derived from commercially available screening compounds (eMolecules screening compounds), literature reports (ChEMBL) and patent data (SureChEMBL), theoretical ring systems (VEHICLe), and commercial reagents (eMolecules building blocks).
Larger fragment databases are split based on the frequency of occurrence of the fragments.
Spark fragment databases based on small molecule crystal structure data from the Crystallography Open Database and Cambridge Structural Database are also available.
Docking in Spark
Use this method to grow ligands and fragments into unoccupied pockets of the target protein, and whenever you wish to find novel results making interactions with the active site of your protein not mapped by an existing starter or reference molecule.
Right: Docking workflow in Spark (PDB: 6TCU). A) A portion of the starter molecule is selected for replacement. B) The selected fragment is deleted. C) A new fragment is attached in a sensible orientation to the truncated starter molecule. D) The pose of the new result molecule is optimized using Lead Finder™.
Easy to use interface
- Quickly generate a range of novel molecules from an initial structure
- Profiling and scoring help you choose the most innovative and tractable leads with the properties you need
- Use filters to find the result with the right mix of physicochemical properties and biological activity
- Visualize results in detail side-by-side, or cluster similar chemical scaffolds
- Search for moieties from real, published or unexplored compound databases
- Create your own custom databases based on the reagents you have available or your proprietary chemistry
Customers say Spark is the best scaffold hopping software they have ever used
Spark works in electrostatic and shape space so it can match the nature of your molecules better than any other tool. When you grow ligands into new space, or link ligands from different regions of your protein active site, Spark gives you complete control. You can choose to be guided by your knowledge of existing ligands, your reagent availability, or by the ideal property profile.
Testimonials from Spark users
One of the compounds discovered with Spark is now our key lead against this target and further analogue synthesis is underway. Spark has certainly helped direct us towards some novel and very useful SAR on this occasion.
Laurent Rigoreau, Group Leader Medicinal Chemistry, Cancer Research Technology Discovery Laboratories
Great to see how this scaffold-hopping software has developed over the years and is being refined to take account of the real life problems facing medicinal chemists, in balancing synthetic accessibility and potency with the physicochemical properties required to produce drugs.
Barret Kalindjian, SBK Pharma Consultancy Services Ltd
A very valuable asset for the drug discovery toolbox.
Barret Kalindjian, SBK Pharma Consultancy Services Ltd
Forge and Spark are excellent programs for LBDD.
Dr. Prija Ponnan, Department of Chemistry, University of Delhi
Students who use Cresset tools tend to gain an affinity with a number of med-chem concepts far earlier than those who do strictly organic projects, for example using Spark to identify new frameworks that possess favorable properties and which can then be synthesized in the lab via a novel reaction.
Dr Raj Gosain, University of Southampton, UK