Cresset announces scientific programs for User Group Meetings

Cambridge, UK – April 21st 2015 – Cresset, innovative provider of computational chemistry software and services, is pleased to announce their North American and European User Group Meetings, both taking place in June 2015.

The North American scientific program features presentations from:

  • Cresset, including a sneak peek at the new science to be included in the next software releases
  • Monsanto: ‘Tioxazafen, a new broad-spectrum seed treatment nematicide’.

Companies can also request 1:1 discussions with Cresset’s products and consulting services team.

The European scientific program comprises content from:

  • Cresset
  • BioBlocks
  • Calcico Therapeutics
  • Cancer Research UK
  • Evotec
  • Isogenica
  • Merck Serono
  • Selvita
  • UCB

Computational, medicinal and synthetic chemists also have the opportunity to participate in software workshops covering areas including scaffold hopping, molecule design and virtual screening.

Participation is free of charge and online registration is open now:

Register for North American User Group Meeting

Register for European User Group Meeting

Field Based Chemistry North America and Europe

Cambridge, UK – 12th May 2014 – Cresset, innovative provider of computational chemistry software and services, announces its annual user meetings, ‘Field Based Chemistry North America’ and ‘Field Based Chemistry Europe’. Both meetings combine scientific presentations, product updates, and news on the latest Cresset research. There are also free expert training sessions for Cresset products at each meeting.

The North America meeting takes place on June 11th, 2014 in Cambridge, MA, USA. Presentations will be given by Novartis, Retrophin, Harvard Medical School, leading academics and Cresset scientists.

The European meeting takes place on June 19th – 20th, 2014 in Cambridge, UK. Presentations will be given by scientists from industry, academia and Cresset. This meeting features the panel debate, ‘Deploying modelling tools to medicinal chemists’.

“The Cresset ‘Field Based Chemistry’ meetings are excellent forums for the sharing of ideas, approaches and results, enabling our customers to benefit from combined experiences challenges and successes,” says Dr. Robert Scoffin, Cresset’s CEO. “In our industry, where confidentiality is so important, our customers value the chance to meet with peers and help one another on the path towards our common scientific goals.”

Registration for both meetings is free and is open now.

Presentations from Field Based Chemistry Europe 2013

Following the review of Field Based Chemistry Europe 2013, please find below a selection of presentations made available with the kind permission of the presenters. Click the presentation title to view.

Application of Forge and Spark to develop new drug candidates from lead compounds derived from network pharmacology models
Ben Allen of e-Therapeutics described how network pharmacology can help to identify drugs when nothing is known about their binding. His presentation explained how they use networks to identify the protein footprint of compounds. They use the Cresset tools Spark and Forge for structural ligand-based bioisostere identification.

Conformational sampling tools
María José Ojeda Montes of Universitat Rovira i Virgili described a methodology they have been developing to explore the conformational space around leads. They found that the acceptable reliability for finding the bioactive pose decreased as the number of rotatable bonds increased above seven. They hope in future to generate a database of pre-generated conformations of small molecules with less than seven rotatable bonds, which includes 70% of the small molecules of the Zinc database.

Upcoming features and future horizons
Dr Mark Mackey, Cresset’s CSO described new features, current work and topics that Cresset are looking at for the future.

The trend to outsource computational chemistry
Dr Martin Slater, Cresset’s Director of Consulting outlined the increasing fragmentation of the pharmaceutical industry and the decrease in R&D spend that have contributed to the increase in outsourcing of all aspects of drug discovery, including computational chemistry. He described a recent consulting project for Mission Therapeutics to produce a small compound library. Further reading: The trend to outsource computational chemistry; Cresset services.

Kinetics versus thermodynamics – insight into protein function
Dr Andy Vinter, Cresset’s founder and Chairman described the difference between the active β2AR/”G” vs the inactive β2AR. He explained how studying the difference between the very similar active agonist and the inactive antagonist will reveal a lot of information and will be a useful test of the XED force field.

Review of Field Based Chemistry Europe 2013

Following on from the successful Field Based Chemistry North America last month, the scientific program of Field Based Chemistry Europe took place at Madingley Hall, Cambridge on 20th June 2013. A mixed program of speakers from academia and industrial organizations presented on a range of topics related to field based computational chemistry.

This blog gives a short overview of each speaker’s talk. Links will be added to the presentations as they become available.

In ‘Field points and structure based drug design’, Dr Gianni Chessari, Director at Astex Pharmaceuticals, presented the Astex approach to field points.

Dr Chessari described a case study of an X-linked inhibitor of an apoptosis protein in which field points were used to understand SAR and the ligand-protein interaction.

He concluded that a good understanding of the electrostatic interactions between ligands and proteins leads to efficient fragment optimisation and he noted that small molecule Cresset field points compare well with field points derived from ab initio methods.

Dr Mark Mackey, Cresset’s CSO, described ‘Upcoming features and future horizons’ for Cresset. He described the following new features:

  • The new XED FF3 released in Cresset products last year,
  • Activity cliffs and disparity analysis, available soon as a beta version,
  • The recently released BlazeGPU that gives a 40 fold speed increase to Blaze.

He also described the work that Cresset is doing on:

  • Calculating protein similarity
  • Calculating off-target effects using 3D descriptors and features.

Dr Mackay also touched on topics that Cresset are looking at for the future:

  • More work on analyzing protein fields.
  • Extending disparity analysis to qualitative models for SAR.
  • Extend off-target model work.
  • Building field based ADMET models.

In ‘Application of Forge and Spark to develop new drug candidates from lead compounds derived from network pharmacology models’ Dr Ben Allen of e-Therapeutics described how network pharmacology can help to identify drugs when nothing is known about their binding. His presentation described how they use networks to identify the protein footprint of compounds. They use the Cresset tools Spark and Forge for structural ligand-based bioisostere identification.

Dr Tim Cheeseright presented Cresset’s new Activity Miner module, which will soon be available as a plug-in for Torch or Forge. Activity Miner measures 2D and 3D similarity and compares it to activity to create a disparity score. The results can be displayed using four different views:

  • A colour coded disparity matrix that shows the disparity values for all pairs of molecules. This makes it easy to visually identify areas of high SAR.
  • A disparity table that shows the pairs with the highest disparity value. The table also includes physical activity and structure.
  • A cluster view that shows the molecules clustered by field similarity, but color coded by activity. This can be used to identify changes of activity within clusters.
  • An activity view that includes a focus compound. Other compounds are displayed, ordered by their similarity to the focus compound. These compounds are colour coded by their disparity, making it easy to identify the field changes that have resulted in the change of activity.

‘New drugs from old compounds’ described Re-Pharm, a new offshoot of Cresset. Re-Pharm uses Cresset software to find candidate compounds for reprofiling in order to find a new clinical use for an existing treatment.

After lunch, Dr Daniel Kuhn, of Global Computational Chemistry, Merck Serono presented, ‘How to convince your medicinal chemist – from 3D QSAR to scaffold hopping’. He described a 3D QSAR project using Forge and a scaffold hopping project using Spark.

Spark provided solutions intuitive to medicinal chemists which have been picked up for synthesis. He pointed out that good communication is essential to successful work with medicinal chemists. In particular, one of the strengths of Spark is being able to copy and paste solutions straight into chemical drawing tools such as ISIS Draw.

Dr Ian Wall from GlaxoSmithKline presented ‘Computational Approaches in fragment based drug discovery’ in which he described several in-house computational tools they have developed to help medicinal chemists get access to the maximum amount of data to inform their compound selection.

He outlined their approach to fragment based drug design and emphasised the importance of optimising fragments to maximise their activity before growing them.

In ‘The trend to outsource computational chemistry’ Dr Martin Slater, Cresset’s Director of Consulting, outlined the increasing fragmentation of the pharmaceutical industry and the decrease in R&D spend that have contributed to the increase in outsourcing of all aspects of drug discovery, including computational chemistry. He described a recent consulting project for Mission Therapeutics to produce a small compound library. Further reading: The trend to outsource computational chemistry; Cresset services.

María José Ojeda Montes of Universitat Rovira i Virgili presented ‘Conformational sampling tools’. She described a methodology they have been developing to explore the conformational space around leads. They found that the acceptable reliability for finding the bioactive pose decreased as the number of rotatable bonds increased above seven.

They hope in future to generate a database of pre-generated conformations of small molecules with less than seven rotatable bonds, which includes 70% of the small molecules of the Zinc database.

Dr Peter Hunt, Senior Research Investigator at Novartis, presented ‘Crystals, Co-formers and Cresset – adventures on the high C’s’. Co-crystals are a crystalline material consisting of 2 or more electrically neutral molecular species which are solids at ambient temperature. He gave the example of carbamazepine, which is very prone to forming co-crystals. However, the solvate furfural is toxic. The challenge is to take the toxic solute and to replace it with an acceptable co-former.

He noted that Cresset software generates ideas as to what might work and what might work better. They believe that co-crystal screening will grow in importance and the ability to rank acceptable co-formers will become a need.

The final presentation of the day was by Dr Andy Vinter, the founder and Chairman of Cresset. His talk, entitled ‘Kinetics versus thermodynamics – insight into protein function’ described the difference between the active β2AR/”G” vs the inactive β2AR. He described how studying the difference between the very similar active agonist and the inactive antagonist will reveal a lot of information and will be a useful test of the XED force field.

Dr Tim Cheeseright of Cresset closed the meeting by thanking the speakers.

Presentations from the Spring ACS 2013

The spring meeting of the ACS saw Cresset presenting a comparison of Spark, with a quantum mechanical approach NEAT that was published last year, and discussion on the best way to prepare datasets protesting virtual screening and the development of the BlazeGPU.

Tim Cheeseright presented a detailed study on the use of Spark for scaffold hopping on Sildenafil. He showed that using the XED force field gave comparable results to those published by Pfizer. He speculated that this was a combination of working in product space and the unique abilities of Cresset’s force field to model aromatic species. The full presentation is accessible below.

Tim also presented work that we have been doing on the assessment of virtual screening performance. Mark Mackey is now writing this up as a paper and hence the slides are not currently available. If you would like to discuss our thoughts then please get in touch.

Simon Krige presented the work he has been doing on the conversion of Cresset’s core alignment technology from Fortran to openCL. He outlined the many advantages of working in a language that enables code to run on both central and graphics processing units. He showed Cresset’s virtual screening system, Blaze, has been speeded up by a factor of 45 when running on the latest generation of accelerated device for Nvidia. The full presentation is shown below.

 

Scaffold Hopping for Aromatic Rings

How GPUs Can Find Your Next Hit

 

We will be discsusing aspects of these presentations at our european user meeting in Cambridge, June 20,21, please join us!

Countdown to Field Based Chemistry, Novartis, Cambridge, MA on May 14

We’re finalizing plans for Field Based Chemistry North America.

Workshop sessions are already fully booked but we’re running a waiting list so let us know if you’re interested and we’ll contact you in the event of a cancellation.

There is still space left to attend the scientific program which has the following great line up of speakers who will provide an informative day.

* Register FREE now *

 

Scientific Program

Upcoming features and future horizons

        Dr Mark Mackey, Chief Scientific Officer, Cresset

Ligand-based virtual screening: How can we do better?

    Rajeshri Karki, Novartis

Using field based chemistry methods to understand sequence-specific protein-DNA interactions

    Daniel Barr, Utica College

The trend to outsource computational chemistry

    Dr Martin Slater, Director of Consulting, Cresset

New drugs from old compounds

    Dr Robert Scoffin, Chief Executive Officer, Cresset

Drug hunts with sparkV10: case studies from the literature and current campaigns to develop immunokinase inhibitors

    Dr Alfred M Ajami, DCAM Pharma Inc.

Performance of XedEx and other conformational search algorithms on flexible scaffolds

    Dr Patrick McCarren, The Broad Institute

Identification of a novel inhibitor of HIV-1 entry using scaffold-hopping and bioisosteric replacement

    Dr Simon Cocklin, Drexel University

March 2013 Newsletter

This month, Dr Rae Lawrence discusses a workflow that encompasses the elucidation of a reasonable binding mode pharmacophore template with forgeV10. She demonstrates how that template can be used for virtual screening to find diverse chemical series and how the results can ultimately be used for scaffold-hopping and lead optimization. Rae also highlights the experimental set up in blazeV10 and the pitfalls associated with multiple-molecule templates as the virtual screen seed. Read on to find out more.

forgeV10.1 Released

A new version of forgeV10, the computational workbench to understand SAR and design, is now available and is recommended for all users. Of particular note are:

  • the ability to apply differential weights to multiple reference molecules.
  • a new context sensitive menu on the 3D window.
  • support for viewing blazeV10 result files and legacy FieldView projects.
  • an improved workflow for molecule design.
  • improved pdb download and processing.

Contact us to upgrade or get a free evaluation.

Great Business Returns from Outsourcing

Concluding this series of blog posts, Dr Martin Slater explains Cresset’s very simple fee-for-service model for answering specific questions and addressing key issues in the discovery and early development phases of a new drug.

Cresset’s consulting team has demonstrated the value of outsourcing computational chemistry by delivering valuable results for many clients, proven in terms of patented scientific discoveries that have led to solid business returns.
Read the full article.

European User Meeting

On June 20th, speakers from Merck Serono, e-Therapeutics, Innovative Medicines Group, Trinity College, Dublin and Cresset will present during the scientific program in Cambridge, UK.

Workshop options for computational chemists:

  • Using cloud based virtual screening to find new leads.
  • Rapidly generating new scaffolds.

Workshop options for medicinal chemists:

  • Deciphering complex SAR.
  • Designing imaginative and effective compounds.

Register FREE now.

North American User Meeting

The scientific program includes speakers from Novartis, Broad Institute, Innovative Medicines Group, Utica College and Drexel University as well as Cresset.

Workshop option for computational chemists:

  • Rapidly generating new scaffolds.

Workshop option for medicinal chemists:

  • Designing imaginative and effective compounds.

Book early as we have limited places for this meeting on May 14th in Cambridge, MA. Register FREE now.

Meet us at ACS New Orleans


Meet our experts on booth 706 in the main exhibition hall or outside the COMP sessions at the Morial Convention Center. We’re also presenting on “Scaffold hopping”, “False false positives” and “How GPUs can find your next hit”; see when and where you can hear us.

Field Based Chemistry North America and Europe 2013

Welwyn Garden City, UK – 5th February 2013 – Cresset, innovative provider of chemistry software and services, announces Field Based Chemistry Europe 2013 and Field Based Chemistry North America 2013, two scientific meetings on the use of fields in the design and discovery of small molecules.

The events are of interest to researchers who want to: make the best possible compounds; shorten optimization processes; create or improve IP position by patent-busting or patent expansion; generate new leads, even in crowded therapeutic areas; develop lower-risk and lower-cost strategies for the discovery of new chemical entities.

Dr Robert Scoffin, CEO at Cresset says, “The Field Based Chemistry meetings build on our previous successful user group meetings. This year we look forward to welcoming individuals from commercial, research and academic organizations who are keen to explore what makes Cresset’s software and services unique.”

Field Based Chemistry North America 2013 takes place on May 14 at Novartis Institutes for BioMedical Research, Cambridge, MA. Speakers include Dr Patrick McCarren from The Broad Institute. Scientists and researchers are invited to submit abstracts for oral presentations by March 15, 2013. The meeting is offered free to delegates. http://www.cresset-group.com/fbcna2013/

Field Based Chemistry Europe is on June 20 to 21 at Madingley Hall, Cambridge, UK. Scientists and researchers are invited to submit abstracts for oral presentations and posters by March 15, 2013. The meeting is offered free to delegates. http://www.cresset-group.com/fbce2013/

End of Year Message from CEO

Earlier this year Dr Andy Vinter, founder of Cresset, shared in our blog that he chose the company name because “Cressets bring light to a dark world and herald new events. Field technology sheds new light on the way we think about molecules binding and ‘Cresset’ is a good name for a company that wants to share these ideas.”

Cresset is as good a name now as it was a decade ago, and it signals our continuing goal to illuminate discovery research through the application of robust science. Our methods are constantly being developed and I’m pleased to say that they are endorsed by our enthusiastic customers and I would like to thank you for the real partnership that we have with you.

2012 has been a time of consolidation and growth for Cresset. Our developers, headed by Mark Mackey and Tim Cheeseright, have worked tirelessly to shape our software into a comprehensive range of tools that fits into the work flow of our customers. I am delighted with the new products and their fiery new names. Torch, Forge, Spark and Blaze are thoroughly professional tools that offer Cresset’s excellent technology in highly productive software environments.

Meanwhile, the consulting side of the business has been thriving. Martin Slater’s current blog about consulting services highlights the reasons why people choose to outsource their computational chemistry to Cresset. He gives examples of the great synergies that have come about through the application of our expertise to the many and varied research challenges that our customers bring us.

It was great to meet old and new faces at our US and EU User Group Meetings this year. People tell me how encouraging they find these events and how much they enjoy the chance to share ideas and discuss how Cresset software is informing their research. A particular highlight for me was hearing how Peter Ertl of Novartis is using Cresset tools embedded within a workflow to create new active molecules. I’m looking forward to meeting many more of you at our 2013 meetings in the summer: “Field Based Chemistry North America 2013“, Cambridge, MA on 14th May and “Field Based Chemistry Europe 2013“, Cambridge, UK on 20th to 21st June. Further details will follow in our January newsletter. I hope you will book the dates in your diary now!

This summer we welcomed David Bardsley on board as our new Sales Director. I know that he has already been in touch with many of you to find out how we can best meet your computational needs. David is based in the UK and, together with Rae Lawrence and Carlton Squires in the US, is always keen to hear from new and existing customers.

This year we’ve taken the environmentally friendly decision to refrain from sending festive greeting cards. We’ve donated the money saved to the AICR to fund research into the causes of cancer.

As we look forward to 2013 I would like to wish all of our customers and partners every success. We sincerely hope that as we seek ever better understandings of molecular interactions Cresset will continue to make a real difference to your research.

Dr Robert Scoffin
Dr Robert Scoffin
CEO

Review of Cresset European User Group Meeting June 2012

Our scientific programme reflected the wide range of scientific fields involved in drug discovery and the depth of breadth of scientific knowledge that goes into developing software for in silico research. The talks ranged from the force fields involved in protein-protein interactions to the use of NMR technology to understand drug metabolites. Below is a review of each presentation. If you would like further details of any presentation please contact us.

Dr Jon Mason of Heptares opened the day’s scientific talks with an informative overview of his work on the energetics of water networks in proteins. Having worked in this field for over 25 years, he has reached a point where he has found that the computational mapping of water energetics in a protein target has a high correlation with druggable binding sites for targets, or at least with ligandable targets.

Dr Mark Mackey, Cresset’s Chief Scientific Officer gave an overview of the new science that Cresset has been working on, including how conformations are generated, new sampling methodology for 3D QSAR, advances in fragment growing technology with the option to merge results from multiple ligands, and finally an updated force field, FF3 which refines and improves Cresset’s existing XED force field. He also introduced forgeV10, Cresset’s new 3D QSAR environment.
Download the presentation here.

Dr Peter Ertl, Director of Cheminformatics at Novartis shared his Intelligent Automated DEsign (IADE) method for bioisosteric design. His automated fragment replacement system firstly identifies bioisosteric fragments for a given compound and replaces them iteratively to generate several hundred analogs. These are converted to 3D structures using CORINA. Reasonable conformations are generated using Cresset software and the conformation most similar to the target is identified using FieldAlign. He used this method to design the winning molecule in Cresset’s ‘Design a Molecule’ competition in October 2011.

Dr Andy Vinter, Cresset’s Chairman updated us on how he has used the XED force field to normalise proteins and gain insights into the actions of agonists and antagonists. He reminded us that atomic charges do not sit on the nucleus, as some force fields approximate, but rather the real electrostatic charge varies close to the atom, as reflected in Cresset’s unique FF3 force field.
Download the presentation here.

Drug repositioning is an increasingly popular area of drug discovery. The increasing costs of R&D and decreasing return on investment has lead many companies to focus on finding new opportunities based on existing drugs and their templates. Dr Alan Rothaul gave an overview of structure and non-structure based methods of repositioning and showed how structure based re-profiling through fragment swapping can feed into new compound discovery. He pointed out that new intellectual property has to be established and that this is often determined through reformulation.
Download the presentation here.

Dr Ute Gerhard of the University of Hertfordshire demonstrated how the power of NMR and mass spectrometry analysis are used to determine the structure and concentration of drug metabolites. The detection limits for state of the art NMR are now where mass spectrometry was ten years ago. NMR can be used to successfully identify potentially toxic metabolites so that only good quality drug candidates are progressed through the discovery process.
Download the presentation here.

Optibrium and Cresset recently announced a collaboration to combine the power of Optibrium’s StarDrop with Cresset’s FieldAlign. Dr Matthew Segall of Optibrium gave an overview of multiple parameter optimization (MPO) for drug discovery, as delivered in StarDrop. Drug discovery demands that chemists make confident decisions based on complex multi-dimensional data. The challenge is to optimize the vast quantities of data available, while making allowances for data accuracy and weighting.
Download the presentation here.

Dr Ronnie Palin of Redx Pharma gave an overview of their approach to drug discovery by discussing novel lead identification using similarity scores. He explained the best starting point is existing drugs since they are known to hit the target and the majority of the optimisation has been done. Their Redox Switch technology is used to change the chemical structure, then Cresset FieldAlign was used to rank the Redox Switch ideas to give the rapid identification of hits in unexploited IP space. Based on this work they have filed patents in multiple therapeutic areas. He gave the example of changing carboxylic acids while retaining activity. Their anti-viral project started with the known anti-flu compounds zanamivir, oseltamivir and peramivir. Their chemists generated ideas to replace the carboxylic function, then Cresset data was used to score the results and the best results were optimized. The found good correlation between the predicted binding and the inhibition of neuraminidase.
Download the presentation here.

Dr Raj Gosain of the University of Southampton told us about two recent projects that his students have carried out using Cresset software to virtually screen compounds of interest against the ZINC database of screening compounds. In the first case a student started from an unusual squaramide structure, which when it was run through the database identified a new compound that whilst having lower activity was actually a more selective hit. Dr Gosain pointed out that they could not have arrived at this compound with any method other than Cresset software. The second example was looking for an inhibitor of the anthrax lethal factor. Starting from a compound with little potential IP due to existing patents they were able to find a tractable starting point for medicinal chemistry, which had novel structure and was clear of existing IP.

This stimulating mix of talks covered an engaging mix of disciplines including pharmacology, medicinal chemistry and computational chemistry. Dr Rob Scoffin, CEO of Cresset summed up the day by reviewing how Cresset has grown and changed over the last year: “Cresset’s customer base is expanding, there has been rebranding with new product names and organizations. However, our core focus remains the same: to provide the best science with the best customer support”.