MicroCal's iTC200 instrument is up to four times faster than its predecessor, the successful VP-ITC, and requires seven times less sample, opening up many applications in the drug discovery field from hit selection, lead optimisation and binding characterisation.

ITC is a technique used to study interactions between molecules in a label free manner that only needs the reaction to produce a small amount of heat to be produced to allow a reaction to be studied. As such it can be used to study protein-protein, protein-peptide, small molecule-protein and even ionic interactions.

This binding data complements structural data generated by X-ray crystallography, nuclear magnetic resonance (NMR) and molecular modelling (MM) experiments to provide complete structure activity relationships (SAR) to aid in drug design and optimisation processes.

While the technology is still far from a high throughput (HT) technique, this latest release will allow researchers to study 100 lead compounds over a few days, opening up the possibility of studying drug-target interactions at the end of secondary screening programs.

The technique does not require researchers to spend time developing assays and the iTC200 comes equipped with software that assists in experiment design and data processing before outputting the data in Microsoft Excel format for further analysis and data transfer.

According to Dr Tim Flanagan, vice president of Europe for MicroCal, the traditional limitation of the technique has been the large sample volumes needed to accurately measure the heat produced during a reaction.

MicroCal has countered this limitation by reducing the sample amounts needed by a factor of seven, to less than 10ug, opening up the technique to researchers working with sensitive proteins are difficult to make on a large scale during the early phases of drug discovery.

"The major application that the iTC200 will be used for is in the drug discovery world, especially at the back-end of secondary screening programs that involve low sample numbers, as well as in lead optimisation processes," said Dr Flanagan.

He continued by explaining that ITC has not been widely used in drug discovery applications because of the large sample amounts needed by traditional instruments but that the technique could give a much deeper insight into binding mechanisms than standard techniques such as florescence assays or SPR (Surface Plasmon Resonance).

"ITC doesn't just tell you whether something binds well or not, it also gives you a really good insight into how the binding occurs from the thermodynamic data generated and help explain what is going on," said Dr Flanagan.

"There are several companies that produce calorimeters that work on nanolitre volumes, but they can't give you the same thermodynamic information because they work on different principles and are not as accurate."

This accuracy allows thermodynamic curves to be generated that show how many drug molecules bind to a target as well as providing information about the enthalpy and entropy of the binding reaction.

The enthalpy data can suggest how much hydrogen bonding is involved in the interaction, while the enthalpy is related to factors such as conformational changes or how much water is released.

"The real power of the technique is in comparing changes that you have made to your molecule in lead optimisation experiments and allow users to study how the binding properties change on modifying the drug candidate," said Dr Flanagan.

To further increase the throughput of the system the company is planning to launch an automated version in 2008, the Auto-iTC200, which will combine all the benefits of the iTC200 with full automation allowing users to conduct up to 50 experiments per day.

Owners of the iTC200 will be able to have their instruments upgraded to the fully automated system after market, allowing them to run up to 384 samples completely unattended.