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Making sense of mitochondria
CORK, Ireland & SHANGHAI, China—Biotechnology company Luxcel Biosciences Ltd. and HD Biosciences Co. Ltd., a preclinical drug discovery contract research organization (CRO), have entered a strategic partnership to co‐market and provide new assay technologies for preclinical drug safety services. Under the terms of the agreement, HDB will gain access to Luxcel’s state‐of‐the‐art assays and technologies for assessment of mitochondrial function, toxicity and metabolism.
Mitochondrial dysfunction is a major contributor to drug‐induced toxicity, postmarket drug withdrawal and black box warnings for hepatic and cardiac toxicity, according to Luxcel. A major focus of the collaboration is the Respirometric Screening Technology (RST/OCR) assay, originally developed by Luxcel in collaboration with Pfizer Inc.
An article in Nature Protocols in 2007 explains, “Mitochondrial dysfunction has been associated with a variety of currently marketed therapeutics and has also been implicated in many disease states. Alterations in the rate of oxygen consumption are an informative indicator of mitochondrial dysfunction, but the use of such assays has been limited by the constraints of traditional measurement approaches. Here, we present a high-throughput, fluorescence-based methodology for the analysis of mitochondrial oxygen consumption using a phosphorescent oxygen-sensitive probe, standard microtitre plates and plate reader detection. The protocol describes the isolation of mitochondria from animal tissue, initial establishment and optimization of the oxygen consumption assay, subsequent screening of compounds for mitochondrial toxicity (uncoupling and inhibition), data analysis and generation of dose-response curves. It allows dozens of compounds (or hundreds of assay points) to be analyzed in a single day, and can be further up-scaled, automated and adapted for other enzyme- and cell-based screening applications.”
A significant advance of the RST assay vs. the commonly used Glu/Gal assay is its ability to accurately differentiate specific mitochondrial toxicity from non‐specific toxicity, as well as un-couplers of mitochondrial function from inhibitors. The RST assay is fully validated in high-throughput format and in weekly production mode at HDB in Shanghai, providing clients with high-quality mitochondrial toxicity assay results with cost-effective and quick turnaround service. The assay can identify mitochondrial liabilities in a variety of drug classes, leading to broad industry acceptance.
According to Dr. Peiyuan Lin, HD Bioscences’ senior vice president of research and development services, “HDB offers a full range of in-vitro toxicology services including safety profiling panels (Safety Assess), as well as cardiotoxicity, hepatotoxicity, genotoxicity and cytotoxicity screenings. Luxcel’s growing portfolio of proprietary mitochondria toxicity, bioenergetics and metabolism assays is highly complementary to our current offerings and provides early and effective identification of mitochondrial liabilities for our clients’drug discovery programs.”
“HDB’s preclinical service brings its clients the most up-to-date and valuable assays and tools to advance the drug discovery process,” said Dr. Ian Hayes, commercial director of Luxcel. “This joint effort will leverage the extensive expertise and capabilities from both sides.”
Founded in 2002, Luxcel Biosciences was and is an award-winning provider of cost-effective, easy-to-use fluorescence-based in-vitro cell test kits targeting cell metabolism, bioenergetics and drug toxicity applications. HD Biosciences is a biology‐focused preclinical drug discovery CRO with headquarters in Shanghai and operation facilities in Beijing and San Diego. The company offers comprehensive research and development services to global pharmaceutical and biotech industries around target validation, plate‐based pharmacology, hit identification and lead discovery, therapeutic antibody discovery and in-vivo pharmacology. The company currently collaborates with eight of the 10 largest pharmaceutical companies in the world and has established strategic partnerships with impacts to their portfolios.