Looking to streamline the drug discovery process, Serenex Inc. was formed to exploit rationalization technology.

The company was first funded last June by Newton, Mass.-based Mediphase Venture Partners, with whom Serenex co-founder and President Robert Dishman is a partner. Other founders include biotech veterans George Young and Steve Hall, as well as Tim Haystead, a professor of pharmacology at Duke University in Durham, N.C. While at the University of Virginia in Charlottesville, Haystead developed the technology now licensed to Serenex.

The company moved into 14,000 square feet of built-to-order office space in Durham, with lab space and automated equipment designed to exploit the technology. Poised for what Dishman called rapid growth, Serenex currently employs 18 people.

Its Functional Proteome Fractionation and Proteome Mining technologies are designed to create high-throughput, simultaneous identification of biologically active compounds and their physiological targets in large numbers.

The Functional Proteome Fractionation technology uses proteome capture ligands that are naturally occurring bioactive molecules required in vivo to enable normal cellular processes. The ligands capture functionally related sub-proteomes of known therapeutic significance for applications such as high-throughput differential display studies.

"The patent is on using a natural ligand - in this case ATP - bound to a matrix such that the ATP will interact with all the proteins that it is exposed to in the same way it would in solution in a cell," Dishman said. "Only those proteins in the sample that bind to ATP bind to the column, typical of affinity interaction."

Dishman said ATP captures up to 4 percent of the total human proteome - specifically all kinases, a number of metabolic enzymes and other proteins.

"There are about 4,000 different targets we can immobilize using Functional Proteome Fractionation," he said.

He said the company continues to work on several other unnamed ligands that Serenex plans to patent.

To decide whether proteins eluted from the test are potential drug targets, they enter an automated process by which they are separated on a gel and run through a mass spectrometer.

"It may be a protein of no interest, physiologically or pharmacologically," Dishman said. "Or it might be a protein that could be a known target. So when that's the case, you have simultaneously discovered a lead compound and the target."

Serenex is developing a single workstation on which 3,000 compounds per day can be exposed in parallel to the Functional Proteome Fractionation technology.

"We're doing millions of experiments almost simultaneously," Dishman said.

While the technology can be used to search for new drug targets, it also can be used to determine toxicity and locate what parts of molecules cause side effects instead of create therapeutic action. Serenex also plans to use the technology to rehabilitate drugs that failed in late-stage clinical trials or were pulled from the market because of side effects.

"We can figure out quite easily which face of that drug binds to the target in a therapeutically important fashion, which faces don't seem to make any difference at all, and most importantly, perhaps, which face is associated with the off-target interaction," Dishman said.

He said Serenex has entered deals with two pharmaceutical companies, and would continue to look for deals by which it could generate more intellectual property for itself. Dishman said Serenex's technology delivered what its partners sought, and at the same time additional applications were discovered. The company plans to make deals for any unexpected results found during collaborations, gaining all or some of the intellectual property around a target's serendipitous indication.

Four other deals with large pharmaceutical companies are in negotiation, he said.

"Each of our deals will be associated with gaining significantly more IP [for Serenex] while doing work on other companies' compounds," Dishman said, "or buying our own libraries."

The company is developing a patent application for a target for rheumatoid arthritis and has shown the mechanism of action for a 50-year-old drug. Dishman said Serenex has identified targets responsible for toxicity in known drugs, as well as discovered therapeutic leads and their physiological targets simultaneously.

Though Dishman declined to specify Serenex's valuation and its money raised to date, he said it has an offer sheet for a significant Series B round of financing.

"In the next year we'll establish all the automation and the huge amount of bioinformatics we'll use to keep track of all of this," he said.