X-Ray Technology Enables Drug Development for Effective Treatment for Melanoma and Other Diseases

The drug, Zelboraf (vemurafenib), has just received US Food and Drug Administration (FDA) approval. In showing the structures of diseased and disease-causing molecules at their basic level, these extremely bright light sources enable scientists to suggest potential new treatments.

The approach was developed at the US Department of Energy’s (DOE; Washington DC, USA) national laboratories. “This technology is a wonderful example of how innovations at our national laboratories lead to discoveries in a wide variety of fields,” said energy secretary Steven Chu. “In this case, we are pleased to have been involved in research that has shown great promise in the battle against life-threatening melanoma.”

An increasing number of drug discovery companies and medical researchers are turning to the powerful X-ray facilities at the DOE national laboratories to probe the causes of disease and develop new treatments. Researchers from Plexxikon, Inc. (Berkeley, CA, USA) , the drug discovery company that developed the melanoma treatment, used X-ray light sources at three national laboratories--SLAC National Accelerator Laboratory (Menlo Park, CA, USA), Argonne National Laboratory (Argonne, IL, USA) , and Lawrence Berkeley National Laboratory (Berkeley, CA, USA)--to determine the specific, three-dimensional (3D) protein structure of a mutated enzyme that instructs melanoma cancer cells to multiply uncontrollably.

The researchers used a technique called macromolecular X-ray crystallography to develop a drug that would prevent the enzyme from doing this. The newly FDA-approved drug, Zelboraf (vemurafenib), was extremely successful during clinical trials in disrupting the disease and extending the lives of those diagnosed with it.

“Plexxikon’s drug discovery approach is critically dependent on harnessing the power of X-ray crystallography, and the role of DOE facilities in enabling the development of compounds like vemurafenib has been fundamental,” said Gideon Bollag, senior vice president for research at Plexxikon. “With the insight we gain from the three-dimensional structures, we have an atomic road map to rationally optimize our drug candidates.”

In addition to this treatment for melanoma, the extremely bright light sources at these Office of Science labs have revealed new insights into diseases such as Alzheimer’s disease, swine flu, autoimmune disorders, bird flu, hepatitis, and the common cold. In revealing the structures of diseased and disease-causing molecular entities at their basic level, the tools for discovery enable scientists to suggest potential new treatments.

The Department of Energy supports five of these advanced X-ray light sources, which are typically football field-sized installations optimized to generate precise, high intensity X-ray beams. Scientists from across the United States and worldwide are actively taking advantage of these scientific user facilities at the national laboratories to make discoveries in a diverse array of disciplines ranging from advanced energy research and materials science to biology and medicine.

Related Links:
US Department of Energy
Plexxikon
Argonne National Laboratory