With the number of protein structures growing exponentially, an increasing number of companies are focusing their efforts on structure-based drug design. One of the latest additions is Plexxikon of Berkeley, Calif., founded in December of 1999 by a team of scientists with expertise in cell signaling proteins and their potential as drug targets.
“The idea is to use this kind of expertise with the power of structural analysis to provide insights into leads and shorten the process of drug design,” said Jack Dixon, a member of Plexxikon’s scientific advisory board and professor in the department of biological chemistry at the University of Michigan Medical School.
Two of the founders, CEO Peter Hirth and Joseph Schlessinger, worked together for 10 years at SUGEN, a drug company concentrating on protein kinases that was bought by Pharmacia in 1999. Sung-Hou Kim, another founder, is well-known in the structural biology community for his work on signaling systems both in prokaryotes and eukaryotes. The impetus for starting the company didn’t come as a revelation “in the middle of a sleepless night,” but rather out of conversations between Hirth and Schlessinger, who also convinced Kim to join them, Hirth said.
Plexxikon is initially focusing on four undisclosed protein families — presumably involved in cell signaling — and is planning to add more families next year. “Choosing the subset of molecules to look at, the potential targets, is probably one of the more important [tasks],” said Dixon.
To design lead compounds against those targets, Plexxikon is combining x-ray crystallography, molecular modeling, and chemistry. First, Plexxikon scientists hope to identify chemical “scaffolds,” or molecules that bind to a wide range of members of a protein family. If they find a promising scaffold, they plan to develop these into more selective and high-affinity drug leads.
In fact, just last week Plexxikon signed an agreement with Scynexis, a company specializing in synthetic organic chemistry based in Research Triangle Park, NC, to obtain access to Scynexis’ compound synthesis technology.
In contrast to companies like Syrrx and Structural Genomix, Plexxikon is not pursuing a high-throughput crystallography approach. Yet, according to Hirth, the company regards Syrrx — along with Vertex and large pharmaceutical companies — as its primary competitors.
In its first year, Plexxikon has worked on raising funds and getting its research started. After completing an $8.2 million round of venture capital financing this May, the company opened a 10,000-square-foot laboratory in the summer and will double this space in January 2002. So far, the company has taken on 18 people, but “a startup company changes daily,” Hirth said. “We are hiring like maniacs.” Plexxikon is also hoping to complete a second round of financing in the next few months.
On the scientific side, the company has developed a collection of compounds and is in the process of filing several patents for co-crystal structures, Hirth said. He is hoping to develop more chemical scaffolds for two of the protein families next year.
— JK