How has this evolution helped both pharmaceutical companies and patients?
The combination of XRD, NMR and MS with molecular dynamics enabled the pharmaceutical industry to tackle more challenging drug development. In 2003, more than 40 compounds, developed using structural information (Structure Based Drug Discovery - SBDD), entered clinical trials, and seven were approved. Nevertheless, many protein target structures remained unsolvable, or at the cost of compromises that were known to potentially affect the understanding of the mechanisms. Amino acid mutations or deletions like the membrane proteins families, and among them many of the G-protein-coupled receptors (GPCRs) that are known to be crucial targets of the molecular pharmacopoeia, could still not be addressed with these technologies.
In 2017, Jacques Dubochet, Joachim Frank, and Richard Henderson won the Nobel prize in chemistry, celebrating the cryo-EM “Resolution Revolution.” Thanks to sample preparation, image processing, and new technological breakthroughs, it is now possible to obtain a three dimensional structure of proteins (including the GPCR families) at near atomic resolution with the so called “single particle analysis” by cryo-EM. This led to the first structure-based drug discovery studies. Cryo- EM has changed the way scientists learn about neurodegenerative diseases, pathogens and cancers because of its ability to provide them with an unprecedented look at the structures of proteins and provide new insights in disease mechanisms. Understanding the structure of viruses and proteins helps determine how they function, potentially leading to prevention or treatment of the diseases they cause. With this breakthrough, new biological mechanisms will be unraveled, and pharmaceutical companies will be able to improve or create new drugs and provide new treatments to patients.
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How has the company helped the pharmaceutical industry enhance its knowledge of protein and protein-like structures over the last 20 years?
Thermo Fisher helps large organizations and smaller biotech companies decrease their time-to-market from early drug development to clinical trial by offering a wide range of innovative technologies.
Thermo Fisher’s genomics tools enable the massively parallel protein biochemistry required in drug discovery to understand the structurefunction relationship. Among many applications, high resolution mass spectrometers were developed to characterize proteins and their ligands and to detect biomarkers to diagnose a disease or to assess a drug action. Thermo Fisher’s arsenal also encompass flow cytometry and fluorescent high throughput imaging techniques based on antibodies bound to the protein of interest. Finally, the recent cryo-EM “resolution revolution” enables scientist to visualize at near atomicresolution functional proteins complexes in their near native states.
Specifically, what products/services/technologies does Thermo Fisher currently offer to assist pharmaceutical clients to bring discovery and develop safe and effective protein and protein-like drugs to market?
Scientists often need to combine various techniques in order to achieve their research goals. Because of time pressure to bring drugs to market and an increase in scrutiny for resource allocation, scientists must choose methods wisely to bring protein-like drugs to market safely and efficiently. We provide complete workflows, from cryo-EM structural determination of macromolecular complexes in native state to 3D reconstruction of tissues and cells. Our solutions help unlock the mysteries of underlying protein functions and cellular processes, bridging the gap between basic science and translational therapeutics.
In addition, we offer customers an “Accelerate” program, an applications and service support program that combines multiple components to further accelerate the time to success for new users. It consists of onsite and remote application support, workflow validation to demonstrate the functional capabilities immediately after installation, and other supporting services to help with installation, technical corrective and preventative service. Our customer success management program is specifically designed to support customers on their journey from setting up a cryo-EM lab thru generating the results for their first publications. Through these efforts, we have sped up cryo-EM adoption in new labs and increased efficiency.
How will Thermo Fisher meet this challenge for its current and future clients?
As the world leader in serving science, Thermo Fisher is in the unique position to master all phases of the drug production process from early drug discovery to the drug manufacturing. Our solutions cover a wide variety of research workflows. We also partner with pharmaceutical companies and service centers around the world to help democratize cryo-EM and provide more researchers access to cryo-EM. That way, current and future customers are provided the opportunity to test and use this technology with top-level expertise and state-of-the-art equipment close to the global pharma research and development centers until the required level of knowledge is acquired and in-house equipment is installed.