Monash University Faculty of Pharmacy and Pharmaceutical Sciences, Australia, licenses Cresset’s computational tools

Cambridge, UK – 25th November 2014 – Cresset, innovative provider of computational chemistry software and services, is pleased to announce that Monash University Faculty of Pharmacy and Pharmaceutical Sciences, Australia’s leading pharmacy and pharmaceutical science educators and researchers, has licensed Cresset’s Forge and Spark software. These applications provide extensive capabilities in SAR analysis, ligand-based molecular design and bioisosteric replacement.

“Cresset’s software is used in the R&D departments of the world’s leading pharmaceutical companies. It is great to know that our students will be using the very same cutting edge tools for their molecular design and optimization work,” says Dr David Manallack, Senior Lecturer at Monash University. “Cresset’s software will enhance our teaching methods, helping us to prepare our students for frontline roles in drug discovery and development.”

“Cresset strongly supports academic research. We are delighted that Australia’s Monash University will be using Forge and Spark in their teaching programs,” says Dr David Bardsley, Cresset’s Commercial Director. “These world class tools will ensure an excellent grounding in modern drug discovery techniques for the next generation of Australia’s scientists.”

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Proximagen licenses Cresset’s computational tools for scaffold identification and bioisostere replacement

Cambridge, UK – 18th November 2014 – Cresset, innovative provider of computational chemistry software and services, is pleased to announce that Proximagen, a company focused on the development and commercialization of novel therapeutics for diseases of the central nervous system (CNS), has licensed Cresset’s Forge and Spark software. These applications provide extensive capabilities in SAR analysis, ligand-based molecular design and bioisosteric replacement.

“Proximagen has successfully used Cresset’s computational chemistry tools in the past to generate pharmacophores from known ligands and to identify novel chemical series by scaffold hopping,” says Dr Ed Savory, Deputy Head of Chemistry at Proximagen. “We will be using Spark to identify new drug scaffolds and to make bioisosteric core replacements. Both Spark and Forge are now important and valuable components of our drug discovery program.”

“We are delighted that Proximagen have chosen to further the collaboration with Cresset,” says Dr David Bardsley, Cresset’s Commercial Director. “Cresset’s continual striving for outstanding science delivered in usable software is translating into valuable results for our customers.”

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Unprecedented control over scaffold hopping searches with Spark V10.3

New fragment databases give 25% increase in available chemical space

Cambridge, UK – 30th October 2014 – Cresset, provider of computational chemistry software and services, announces the release of Spark V10.3 for scaffold hopping and R-group exploration. Spark finds biologically equivalent replacements for sections of an active molecule, generating new ideas and helping you escape patent or toxicity traps. New in this release:

  • Significantly improved viewing, analysis and sharing capabilities help identify compounds with the best balance between novelty, synthesizability and physical properties
  • 25% increase in the number of fragments, giving a greater opportunity to find new IP
  • New advanced filters ensure the drug-likeness of results and narrow the search to specific changes that interest you.

“Spark experiments return structures you have thought of yourself, plus new structures that make chemical sense and are totally unexpected,” says Dr Tim Cheeseright, Director of Products at Cresset. “This new release makes it significantly easier to evaluate and share your results. The new tile view lets you select and view the structures and properties that matter most to your project. Individual chemists can flag key results, add notes and share projects with team members.”

“Spark V10.3 gives users unprecedented control over scaffold and fragment searches,” adds Dr Mark Mackey, Chief Scientific Officer at Cresset. “You can focus your search by filtering on SMARTS patterns or physical properties, so that the results all have the physicochemical profile required by your project.

“In addition, we have enlarged the number of reagents for use in lead optimization and hit growing from 150,000 to over 590,000. This provides a rapid assessment of the synthetically available choices around a lead compound, increasing novelty and reducing the design time for new molecules.”

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Spark’s significantly improved results analysis helps you identify the best bioisostere for your project

Web clip: Spark V10.3 – Using Spark’s tile view and tags to rapidly assess scaffold hopping results

Version V10.3 of Spark, Cresset’s computational chemistry software for idea and bioisostere generation, includes the ability to ‘tag’ results with a custom user-defined note that can be used for sorting, filtering, and decision-making. This expands on the ‘favorites’ designation in that tags can be used to explain why a result was flagged as a favorite. For example, you can tag suggested results as being known already, interesting, synthetically unfeasible, or any other designation that you might need.

The tile view of results allows for rapid assessment of the bioisosteric substitution, along with selected properties in a tiled view. This allows for a stream-lining of the visualization of many results from the Spark experiment and can be sorted and filtered the same way as the regular spreadsheet view in the Molecule Table.

See this in action in the web clip below and contact us to find out more.

Using Spark V10.3 to generate novel IP for DPP-IV

The new release of Spark V10.3, Cresset’s chemistry software for bioisosteric replacement, brings new fragment databases and new advanced filters to control the chemical and physico-chemical space on results. In this case study we apply these new features to the search for new terminal groups for a series of Dipeptidyl Peptidase IV (DPP-IV) inhibitors.

Experimental Setup

Ligand from 1X70_Spark DPP4 Case study

We downloaded the pdb file 1X70, loaded this into Spark V10.3, split the file into ligand and protein excluded volume (keeping Chain A only) using the new protein import facility. We selected the head group of the ligand for replacement then chose to search the Chembl_common, VeryCommon, Common, LessCommon and Rare databases.

DPP4_case_study_databases

Before starting the the ‘Accurate but slow’ experiment we altered some of the parameters which have been introduced in this version. First on the ‘Scoring’ tab we limited the number of results to just 200 and improved the minimization of the final molecules by decreasing the gradient cutoff during the minimization to 0.1 kcal/mol/A. Next, on the ‘Size criteria’ tab we reduced the maximum number of rotatable bonds permitted in a fragment to 3.

DPP4 case study_ScoringDPP4 case study_Size criteria

Finally, we used the new ‘Advanced Filters’ tab to control the physical properties of the final molecules so that we only have molecules with a calculated logP within 1 and 3.5 and a TPSA between 40 and 90. As we expect to use these settings in the future they were saved to a new name ‘top200_acc_min_filt’.

DPP4 case study_Advanced filters

DPP4 case study_Save process settings

Calculation

The calculation was performed using Cresset Engine Broker to distribute the calculation from the host (Windows® 7 based) laptop to to Cresset’s Linux® farm. Running on an additional 20 CPUs the calculation took less than 30 minutes to complete.

Results

We used the new tile view to summarize each result. It was configured with the radial plot (setup with Score, MW, logP, TPSA and 2D similarity) for each compound together with selected textual data (Rank, Favorite, Database source, and Unstable flag). The first 30 results are shown in the screen shot below.

DPP4_case_study_tile_results

The first two results are members of the same series as the query (one of which is a known nM inhibitor) which is a nice validation that that the experiment was setup reasonably. These are followed by a couple of 3-oxo-piperazine which is also a known active scaffold for DPP-IV. Interestingly Spark suggests a 3-oxo-tetrahydro-imidazopyrazine at rank 6 which is quite different to the starter molecule and has excellent properties (small shaded area in the radial plot). This is also a known to be active at DPP-IV with the compound shown having a reported pIC50 of 5.9. At rank 9 in the results is a ring opened version of the starter molecule and then at rank 10 a 1,4-diazepanone which is again a known scaffold for DPP-IV. The next few results are similar to previous results or are known DPP-IV scaffolds such as the N-aromatic acyl piperazines.

Looking down the results for a scaffold not already known to be active at DPP IV gives the 3,4-dihydro-1H-pyrido[1,2-a]pyrazin-6-one at rank 29. This looks an interesting replacement with good properties and room for further substitution. The fragment was found from the ‘Common’ database and appears readily available.

DPP4_case_study_result_29
Spark screen shot of result 29 (right) compared to the original ligand (left) showing the negative electrostatic potentials for the heterocycle groups. Both ligands are shown in the protein active site.

Conclusion

These results demonstrate the power of Spark: a simple 30 minute experiment located not only numerous known scaffold replacements, giving confidence that Spark is indeed producing compounds with the desired properties for activity but also structurally-novel suggestions in clear IP space. The new tile view allows the results to be rapidly triaged by eye, allowing you to focus in on the most desirable replacements quickly and easily.

Contact us to find out more.

Nagoya University’s ITbM, Japan, licenses Cresset’s computational chemistry software to accelerate their research

Cambridge, UK – 28th October 2014 – Cresset, innovative provider of computational chemistry software and services, is pleased to announce that Nagoya University’s Institute of Transformative Bio-Molecules (ITbM), creator of cutting edge science, located in Nagoya, Japan, has licensed Cresset’s Forge, the powerful computational chemistry suite for understanding SAR and molecular design.

“The focal point of ITbM is to develop transformative bio-molecules that will be key to solving urgent problems at the interface of chemistry and biology,” says Associate Prof. Ayato Sato, Head of Research Promotion Division and the chief coordinator of ITbM Chemical Library Center, ITbM Nagoya University, Japan. “We are confident that licensing Cresset’s software will accelerate our research to find candidates of transformative bio-molecules.”

“Working with Cresset’s tools has helped me generate new ideas for my projects in various disease areas,” adds Dr. Anupriya Kumar, WPI Postdoc Fellow, ITbM Nagoya University. ”The molecular visualization has made it easier to communicate my ideas to my experimental collaborators, both chemists and biologists.”

“We are delighted that Cresset software is assisting Japanese biomolecular research,” says Dr David Bardsley, Commercial Director at Cresset. “Forge uses the shape and electrostatic character of molecules to create qualitative and quantitative 3D models of activity. It is the ideal tool to assist ITbM in their research.”

ITbM_Cresset

Selvita licenses Cresset’s computational tools for SAR analysis and ligand-based design

Cambridge, UK – 2nd September 2014 – Cresset, innovative provider of computational chemistry software and services, is pleased to announce that Selvita S.A., a drug discovery company located in Krakow, Poland, has licensed Cresset’s Forge and Spark. These applications provide extensive capabilities in SAR analysis, ligand-based molecular design and bioisosteric replacement.

Dr. Mariusz Milik, Head of Computational Chemistry at Selvita says “We are currently focused on target based design, however, as requirements of our projects change, we need to include ligand based approaches in the methods we use. We anticipate using Cresset’s software as a key component in our discovery chemistry capabilities”

“At Cresset we are delighted to see growth in the emerging drug discovery market of Central and Eastern Europe,” says Dr David Bardsley, Cresset’s Commercial Director. “Both Forge and Spark will enhance Selvita’s chemistry capabilities. The Spark reagent databases will enable them to inform synthetic decisions, whilst Forge will give control and insight into their activity data enabling them to plan the direction of their projects with confidence.”

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CloudScientific appointed as Cresset’s distributor in China

Cambridge, UK – 9th July 2014 – Cresset, innovative provider of computational chemistry software and services, announces the appointment of CloudScientific as distributor of their computational chemistry software in China.

“The appointment of CloudScientific provides us with a dedicated channel to deliver our tools to the Chinese marketplace and will enable us to respond to the specific needs of potential customers in China” said David Bardsley, Commercial Director at Cresset. “CloudScientific has an established record of collaboration with its customers. I look forward to working with them to increase our presence in this important market.”

“We are delighted to represent Cresset who have an excellent scientific reputation and bring a portfolio of leading computational chemistry products,” said Andrea Li, Marketing Manager at CloudScientific. “We look forward to introducing these tools to the Chinese market and helping drive growth and enhanced commercial success in the future.”

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Forge V10.3: Significant new science, visualization and integration for leading ligand-based drug design workbench

Cambridge, UK – 3rd July 2014 – Cresset, innovative provider of computational chemistry software and services, announces the release of Forge V10.3. This major new release includes significant enhancements to the science, visualization, and integration of Forge, the computational workbench for ligand-based drug design, including significant enhancements to Activity Miner.

“Activity Miner has been a huge hit since its release as part of Forge last year,” says Dr Tim Cheeseright, Director of Products at Cresset. “Customers have found it invaluable for finding and understanding critical activity cliffs in the SAR landscape. In response to customer requests we have now added selectivity cliffs – the use of multiple activity parameters to look for changes that disproportionately change one activity relative to another.”

“Even though independent tests show that our performance is one of the best, we have still made improvements,” says Dr Mark Mackey, CSO at Cresset. “Forge V10.3 includes improved conformation hunt settings that give significantly fewer, lower energy conformations, enabling you to find the correct alignments even more reliably.”

Major highlights of Forge V10.3 include:

  • Find and understand structure-selectivity relationships in Activity Miner
  • Perfect the design and activity profile of new molecules using 3D-QSAR models for both primary and secondary activities
  • Rapidly analyse large datasets by connecting Forge to cloud or local cluster resources to perform calculations using the Cresset Engine Broker module
  • Create detailed pharmacophores from diverse ligands using the integrated FieldTemplater module
  • Find new chemical intellectual property using Cresset’s Blaze for ligand-based virtual screening directly from your desktop
  • Manipulate complex data within Forge using the new Column Script Editor to automatically modify or calculate molecular properties in the data table.

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Forge V10.3 provides new features aimed at optimization of multiple activities simultaneously through an easy to use interface.

Centre for Chemical Biology & Therapeutics at inStem licenses Cresset’s computational tools for lead optimization and identification

Cambridge, UK – 2nd June 2014 – Cresset, innovative provider of computational chemistry software and services, is pleased to announce that the Centre for Chemical Biology and Therapeutics (CCBT) at The Institute for Stem Cell Biology and Regenerative Medicine (inStem), a state-of-the-art research institute in Bangalore, India, has taken a three year license for use of Cresset’s Forge and Spark software tools for lead optimization and identification. The CCBT, which is directed by Prof. Ashok Venkitaraman (University of Cambridge) in an international collaboration between Cambridge and inStem, seeks to pioneer new approaches for chemical biology and therapeutics through the development of new methods for small-molecule drug discovery. Cresset and Forge will be used in the new computational chemistry group in the CCBT.

Dr. Kavitha Bharatham, who leads the computational chemistry team in CCBT, says “Having used Cresset’s software in my previous role, I am very keen to apply it to our work at CCBT. My experience with Forge and Spark makes me confident that they will be valuable tools for our research. The support I have received from Cresset staff has been excellent, and I am very pleased to introduce their computational tools to CCBT for our lead optimization and identification projects. I am confident that we will achieve our goals.” Prof. Ashok Venkitaraman, who directs the CCBT, adds, “The CCBT aims to pioneer innovative new approaches for using chemical tools to understand the biology of human diseases like cancer, and to develop new avenues for therapy. I am pleased that we will be licensing Cresset’s software for our work.”

“We are delighted that the CCBT at inStem has chosen to work with Spark and Forge,” says Dr David Bardsley, Cresset’s Commercial Director. “Spark will enable them to generate novel and diverse structures and to use reagent databases to inform synthetic decisions. Forge gives the CCBT control and insight into their activity data enabling them to plan the direction of their project with confidence.”