The total cost of bringing a drug to market has doubled over the past decade, to approximately $2.6 billion, and taking an average of 12 years. The pressure to advance new drugs faster is greater than ever. Timely access to high-resolution molecular structures is essential to modern drug discovery and development, and Single-Crystal X-Ray Diffraction (SC-XRD) is a core technique.
Target discovery and characterization is the first step in development of a new drug. Detailed structural characterization of the protein involved in the disease is performed using SC-XRD. Bruker’s SC-XRD product line allows you to configure the ideal system to match your needs, enabling fast and accurate characterization of the protein directly in your lab. Structure-based drug design utilizes this information to develop lead compounds into viable drug candidates. For example, approximately half of currently available medicines target members of a family of proteins known as GPCRs. An investigation using the D8 VENTURE METALJET determined the structure of a GPCR in under three hours.
Getting leads to clinical trials as efficiently as possible is crucial to the development of affordable medicines. And having immediate access to the right SC-XRD system significantly accelerates lead discovery and reduces the pipeline time to registering Investigative New Drugs (INDs). Bruker’s D8 VENTURE can be equipped with tools to automate data collection, allowing structure determination to continue 24/7, further increasing laboratory throughput. Successful registration of an IND requires the complete and unambiguous structure of the drug compound. SC-XRD is the only method that can determine the absolute structure of organic molecules.
During the drug development phase, it is essential to understand how the active pharmaceutical ingredient (API) packs into the crystalline form, as this influences the stability of the medicine and bioavailability. Each API can crystallize in many different forms and each crystalline form may exist in several polymorphs. SC-XRD is used to understand the molecular structure of the various forms at atomic resolution and is essential to ensure development of a medicine with the optimal properties. The D8 VENTURE can be equipped with accessories to investigate polymorphism under non-ambient conditions, such as high pressure or different temperatures, which may be required during manufacture of the medicine.
Once the absolute structure has been determined with SC-XRD, Powder X-Ray Diffraction (PXRD) is used to maximize yield, perform polymorph screening and confirm excipient purity. Bruker offers a wide variety of PXRD solutions. The benchtop D2 PHASER is simple to use and requires no special facilities. Experimental flexibility is the core feature of the D8 ADVANCE, supporting quick optic and stage changes to support various sample forms and non-ambient conditions. For high throughput analysis, the D8 DISCOVER allows screening of conventional 96-well plates. Production support typically employs the D8 ENDEAVOR equipped with a large sample changer. All solutions can be configured for automated measurement and analysis. In addition, our PXRD solutions are available for cGxP/ 21 CFR Part 11 regulated environments.