Tumor key protein structures are successfully resolved
Recently, published in the international journal Nature a study, researchers from Argonne use high specificity of X-ray crystallography to resolve the hypoxia-inducible factor (HIFs) protein structure, hypoxia-inducible factor tumor response to hypoxia important regulator of the study or the supply of oxygen and nutrients to find new drugs cut cancer cells eventually provide a new way to treat cancer.
The researchers pointed out that the study we first opened the sub-structure to carry ARNT protein HIF1-α and HIF2-α complex, ARNT Asia HIF protein function is to maintain the desired structure; and for these multi-domain structure visualization or can help researchers understand drug binding capacity, but also help promote the later development of new drugs that inhibit tumor effect of HIFs.
HIF proteins that regulate the development of a series of very important cancer gene expression, regulation of the activity of these genes is considered a promising cancer treatment method, currently part of many pharmaceuticals are trying to find drugs can inhibit HIF pathway, the researchers only You can find a combination of a drug candidate called PHDs, PHD can modulate the activity of HIF protein, treatment of anemia, a series of clinical trials in chronic kidney disease, stroke and cancer, there are many in the current PHD inhibitors. The researchers said the study we are looking for HIF drug combination, not binding drugs PHDs provide some help, we are now identified in the structure of HIF complexes in five different channel-like structure, all of these groove-like structure It can be used to develop small molecule inhibitors targeting, these drugs or to inhibit its function by reducing the stability of the HIF.
HIFs suppression drugs might be used to treat solid tumors, because the growth of solid tumors can be more than give their blood supply, which could make cancer cells become hypoxic, open expression to stimulate HIFs regulate cancer cell survival pathway genes including angiogenesis, erythropoiesis, and cancer metastasis increased anaerobic metabolism gene expression; the synergy of all these processes can help promote tumor growth as well as their tolerance to drugs, and ultimately reduce the survival rate.
The next step researchers will conduct a series of patient samples HIF protein mutation analysis, the researchers want to identify the sites of HIF protein is mutated, and to reveal cell dysfunction promote HIF exhibit molecular mechanisms and specific mutation often give HIFs protein structure and function brought activity to help them open or closed gene expression. As researchers HIFs structure, function and regulation mechanism of understanding, the investigator or will develop novel therapies in addition to a series of other therapies for cancer diseases, such as heart disease, fatty liver, diabetes and inflammatory diseases.