Technology transforms drug discovery

Infinity Pharmaceuticals is a drug discovery company that is developing and integrating unique approaches and capabilities in synthetic chemistry, chemical genetics, informatics, and biological screening.

Founded in July 2001, the company is positioned to capitalise on the enormous opportunity resulting from the genomics revolution by providing pharmaceutically active and selective new drug candidates to a broad, expanded range of well-validated biological targets.

Located in Boston, Massachusetts, Infinity has established access to a human capital pool including renowned scientists' prominent entrepreneurs and business executives from the biotechnology, high technology, and consulting sectors' and leading financiers.

Enterprise versions of E-Notebook, ChemACX, and ChemOffice Ultra are playing a significant role in the process and have provided measurable return on investment during their first four months of use. "CambridgeSoft has been an excellent partner," said Andrew Ellicott, application services manager at Infinity Pharmaceuticals.

"Thanks to open, flexible, high-value software like Cambridge-Soft's products, we've established a comprehensive drug discovery software platform that integrates best-of-breed components in under six months." E-Notebook enables scientific breakthrough.

Part of what makes Infinity Pharmaceuticals so special is its commitment to using electronic laboratory notebooks instead of the traditional bound paper notebooks.

This is a major shift for most laboratory researchers and, in many ways, is not possible without a company-wide, top-down commitment.

When you walk into an Infinity chemistry lab, you'll notice E-Notebook running at every bench.

Infinity chemists have embraced E-Notebook and the collaboration and productivity benefits it delivers.

It enables them to record and share reaction designs, LCMS, NMR, TLC and other work-ups and experimental data.

This ability to share information has fostered a team environment where the researchers are part of a community striving towards a common goal.

Each scientist can experience first-hand the road to success.

The following paraphrases an interview with Mike Foley, vice president, chemical technology, and chemists Eva Gordon and Sylvia Georges, as well as remarks made by president and CEO Steven Holtzman, where they described a recent success that was made possible by using E-Notebook.

"We have recently been doing experiments to make a split-pool combinatorial library.

The library is built off of a core template which is attached to a solid phase medium.

Each core template has several sites to which chemical diversity points can be added.

E-Notebook came to the rescue when a problem with a key reaction was jeopardising the entire library project.

An impurity from a reaction was arising that, in many cases, corresponded to a 50% yield in the synthesis of a core template.

This low yield was putting the entire library programme at risk due to the inability to generate enough of the core template in an economical way." "The impurity was detected through thin layer chromatog-raphy (TLC).

The ability to seamlessly jump from electronic notebook to notebook, study images of the TLCs, and compare conditions, is what made this win possible.

It's hard to put a price-tag on this success. Either the project was going to be aborted because we couldn't generate the materials, or the number of compounds produced was going to be compromised." "Since we were all using E-Notebook, we were able to go back and compare the TLC results under various conditions and find a solution to the problem in a matter of 12 hours, versus the 4-6 weeks it would have taken an individual.

From the standpoint of a pharmaceutical business this constitutes a major win - especially if you think of the drug development process as a series of microcycle projects.

If the time to accomplish one of the integral smaller tasks is reduced from weeks to hours, it can mean a difference in years when getting a drug to the market." Examining the results.

"Once all the hard work in the lab is complete, this electronic technology affords everyone access to the information needed to make decisions.

New questions can be raised when studying the data - questions that couldn't be posed before because the TLC plates were often thrown away.

More educated questions can be addressed while studying the results - questions that weren't primary ones when you ran the TLC, but are now very critical in understanding the results.

Another nice feature of E-Notebook became apparent when we wanted to document this success story for a meeting.

It wasn't necessary to go to the chemist (Eva Gordon, for example) for background information.

Instead, the information was extracted directly from Eva's notebook pages and screen shots were taken for use in a presentation.

Eva didn't have to take time out of her busy schedule to provide data to her colleagues. This open work environment, where everyone has access to each other's findings, and in a sense shares ownership, is very exciting.

However, it is also unique because in the traditional scientific world your notebook is often your private piece of property in an enterprise.

Even though everyone understands that the information is proprietary, it's not quite as public as an open book." The presentation.

"In a morning chemistry meeting, further questions were asked about this little phenomenon.

Eva went to the network and pulled up her notebook to view the TLCs and Sylvia did the same for one of her reactions. Never before could topics be discussed at this level of detail. Now when someone asks if you tried the reaction under certain conditions, you can reply that you did, then proceed to show them the results.

It changes the whole conversation from the hypothetical to the real.

The fact that you can flip from your PowerPoint presentation to your E-Notebook and pull up the experiment is a great time saving feature.

Before you would have had to run back to your desk, grab your physical notebook, and put it on the table for everyone to crowd around.

Now you can pull up the TLC plate on the screen, zoom in and make the image as big as a person.

This way you can easily examine all of the spots and know exactly what is going on in that reaction.

This feature alone makes our meetings more effective." "Capturing TLC information in a paper notebook requires that you sketch an image of the spots by hand, or transfer the silica to a piece of tape and paste it in.

The first method is not very accurate and the second fades quickly with time.

Scanning in an image of the TLC plate and annotating it electronically is the best way to permanently archive the information.

Also, since it so easy to do, you can now capture information on all of the TLC plates you run, instead of just those under the best conditions. The equipment to do this is a flatbed paper scanner hooked up to a computer with any image editing software; Infinity uses Visio. The scanner is located in the lab so the chemists can pop on their TLC plate without having to leave the lab.

The scientist scans an image of the TLC plate, annotates the spots, saves it as an image and then pastes it into a Word document.

The individual word documents can then be added to an E-Notebook page.

It can take a while to become profficient at this, like any new technology.

However, we found that after a week or so the most time consuming part was allowing the scanner to acquire the image.

Annotating the TLC images also took some time, but this would have to be done regardless." Infinity Pharmaceuticals has also assembled a procurement automation system from plug-and-play web services.

It combines purchasing and receiving functions from Oracle with the product catalogue services in ChemACX.

ChemACX accelerates library development by enabling chemists to search for chemical building blocks and create shopping lists online.

Its open architecture makes it easy for Infinity to automatically send product information to purchasing and inventory systems, which minimises administrative overhead costs and gets chemicals to the scientists faster.

Biology: the next frontier.

Infinity biologists are researching targets and pathways as well as designing high-throughput and high-content (HTS/HCS) compound screening assays.

Like their counterparts in chemistry, they too are recording experimental data in E-Notebook.

Even though E-Notebook is designed for chemists, it is flexible enough to provide Infinity biologists with similar collaboration and analytical benefits.

Additionally, Infinity scientists are working with the CambridgeSoft product design team to help future versions of E-Notebook and ChemOffice work even better for biologists.