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Jul 1, 2008 (Vol. 28, No. 13)

Firm's Bailiwick Based on Protein-Protein Expertise

Hybrigenics Offers Three Types of Services: Discovery, Validation, and Inhibition

  • In the 1990s the idea of inhibiting interactions between proteins with drugs “was considered silly,” says Luc Selig, Ph.D., director of sales and marketing at Hybrigenics Services (www.hybrigenics-services.com), a company focused on functional proteomics. Back then the pharmaceutical industry concentrated on finding classical targets like enzymes and receptors.

    “There was a myth that protein-protein interactions could not be inhibited by small molecule drugs because their surfaces were too large,” Dr. Selig notes. Nonetheless, he and his colleagues founded Hybrigenics in 1997 as a spin-off from the Pasteur Institute (www.pasteur.fr). The aim was to apply a yeast two-hybrid technology to the discovery of protein interactions. “Hybrigenics is one of the pioneers in defining protein-protein interactions,” according to Dr. Selig.

    In the last few years a growing number of biotechnology and pharmaceutical companies have added drug candidates to their pipelines that are aimed at blocking protein-protein interactions. Recently, three scientific meetings have been dedicated to sharing knowledge about such interactions. Moreover, hundreds of customers have contracted with Hybrigenics to find drug targets and develop compounds based on protein-protein interactions. “So the concept is now accepted,” Dr. Selig says.

  • Discovery Technology

    In the 1990s the idea of inhibiting interactions between proteins with drugs “was considered silly,” says Luc Selig, Ph.D., director of sales and marketing at Hybrigenics Services (www.hybrigenics-services.com), a company focused on functional proteomics. Back then the pharmaceutical industry concentrated on finding classical targets like enzymes and receptors.

    “There was a myth that protein-protein interactions could not be inhibited by small molecule drugs because their surfaces were too large,” Dr. Selig notes. Nonetheless, he and his colleagues founded Hybrigenics in 1997 as a spin-off from the Pasteur Institute (www.pasteur.fr). The aim was to apply a yeast two-hybrid technology to the discovery of protein interactions. “Hybrigenics is one of the pioneers in defining protein-protein interactions,” according to Dr. Selig.

    In the last few years a growing number of biotechnology and pharmaceutical companies have added drug candidates to their pipelines that are aimed at blocking protein-protein interactions. Recently, three scientific meetings have been dedicated to sharing knowledge about such interactions. Moreover, hundreds of customers have contracted with Hybrigenics to find drug targets and develop compounds based on protein-protein interactions. “So the concept is now accepted,” Dr. Selig says.

  • Services Offered

    Hybrigenics Services uses its databases to help clients identify and validate protein-interaction targets and find small molecules to inhibit them. The databases, which contain hundreds of thousands of interactions, provide a reference technology for comparing data and assigning confidence scores for interactions. “The data and our experience improves statistical scores for verification,” says Dr. Selig.

    The firm offers three types of services—Discover, Validate, and Inhibit. This grew out of the platform used by Hybrigenics Pharma, another division of Hybrigenics, to find new cancer drugs in-house. “Selling a core competency that we use for our own R&D pipeline is another guarantee of quality,” explains Dr. Selig.

    Discover uses ULTImate Y2H to find new targets. Validate is a set of tools to help researchers validate the functions of protein interactions in cells. Finally, Inhibit is a screening platform that looks for small molecules and other chemical compounds that block specific protein-protein interactions identified in the first two steps.

    Clients can get help from Hybrigenics Services at any stage of drug development. Nearly 90% of clients are working in the discovery stage, and most are seeking inhibitors for protein-protein interactions.

    “We have hundreds of thousands of compounds in our libraries,” reports Dr. Selig says, “and we always find inhibitors in our assays. We have mastered the protein-interaction technology and have customized assays that find small molecules.”

    About three years ago Hybrigenics Services teamed up with L’Oreal to discover new interactions among skin proteins. Small molecule inhibitors were identified through chemical screening to advance L’Oreal’s research into innovative cosmetics. L’Oreal provided hair and skin samples, and Hybrigenics Services built highly complex DNA libraries, then screened them for interactions using the ULTImate Y2H technology.

    A new interaction between two skin proteins was detected. L’Oreal researchers are currently testing compounds from Hybrigenics’ chemical library, which appear capable of inhibiting the reaction, as starting materials to design novel cosmetics.

  • Internal Pipeline

    Hybrigenics Pharma concentrates on the development of new cancer drugs. The company licensed inecalcitol, an analog of vitamin D, for the treatment of prostate cancer in combination with existing therapeutics.

    “Vitamin D has been associated with cancer development for a long time,” Dr. Selig points out. Vitamin D treatment, however, produces spikes in blood calcium levels that can damage other organs. Inecalcitol is chemically designed to be more potent and less toxic than vitamin D. The analog is in Phase II trials for hormone-refractory prostate cancer in combination with Taxotere.

    An in-house discovery program focuses on ubiquitin-specific proteases, which were targets identified with the ULTImate Y2H platform. Ubiquitin-specific proteases prevent the degradation of cancer-promoting oncogenes. Hybrigenics Pharma is testing small molecule inhibitors of ubiquitin specific proteases to disrupt oncogenes. Some promising compounds are being tested in animal models.



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