Potential Sarcoma Winner
Sarcomas are a rare and heterogeneous class of tumors that do not respond well to treatment.
The researchers conducted a multi-year cross-disciplinary study, during which they went from screening potential drugs to identifying and developing a unique compound, packaging it into nanoparticles and testing it in cell cultures, and then on model animals.
In their study, the scientists targeted the retinoid receptor X (RXR), which is present in large quantities in sarcoma cells, but is practically not produced in healthy cells of the body. Previously, a class of drugs targeting RXR was developed, but they have high toxicity, and the possibility of their use is limited. The researchers also found that the structure of approved drugs does not perfectly match the structure of the receptor. In this regard, they decided to look for a ligand that would fit better. To do this, they analyzed more than 20,000 chemical compounds using computer modeling and selected the most promising of them for subsequent testing, which they then synthesized in the laboratory.
Having synthesized this substance, the researchers faced a new difficulty: the compound did not dissolve in water, which made its delivery to the body almost impossible. To solve this problem, they developed nanoparticles inside which the substance could be delivered to cells. Then the substance was tested for toxicity and efficacy, first on cell cultures, then on mice that were injected with sarcoma cells, and then on pigs.
During these tests, scientists found out that the effectiveness of this substance exceeds the currently used drugs by three times. It not only reduces the size of the tumor, but also slows down the rate of cell division, preventing the cancer from spreading to neighboring tissues. The researchers also did not find any serious side effects, but they note the need for additional and more detailed study of this issue.
After tests for efficacy and toxicity, the scientists decided to check exactly how the test substance works in tumor cells. The data obtained confirmed the initial hypothesis: in both mice and pigs, the substance works the same way – and exactly in the way scientists had planned.
In the near future, the authors want to start clinical studies on dogs with osteosarcoma, as well as studies with an increase in dosage to select the optimal one. Scientists also hope that this substance may be useful for the treatment of other types of cancer, as well as Alzheimer's disease – all diseases characterized by increased RXR activity.
Article by Ye et al. Design, Synthesis, and Characterization of Globular Orphan Nuclear Receptor Regulator with Biological Activity in Soft Tissue Sarcoma is published in the Journal of Medicinal Chemistry.
Anastasia Poznyak, portal "Eternal Youth" http://vechnayamolodost.ru / based on the materials of the University of Illinois: New drug seeks receptors in sarcoma cells, attacks tumors in animal trials.