A few days ago, The New York Times broke the story about the two cases of doping in cycling. On the surface, that might not seem interesting news. We probably will not spend much time on the positive cases of doping are Anabolic.org, as our readers are well aware that the efficiency enhancing drugs (PED) use is entrenched in many sports, agree with him or not. But the story is very interesting times, given the drug involved. In both cases involved FG-4592, also known as roxadustat, which is a new type of erythropoiesis stimulating agent. This drug is still in the research phase, and it is not available as a prescription anywhere in the world. We get a lot of questions about it, and thought that the rapid introduction was in order.
First, let’s discuss how it works. FG-4592 (roxadustat) aims to hypoxia sensing path (how the body perceives low oxygen content). This drug acts as a specific inhibitor of the enzyme prolyl hydroxylase domain (PHD). By blocking its target PHD enzyme preparation stabilizes the protein known as HIF-2 & alpha; (Hypoxia-inducible factor 2 & alpha;), which is largely found in the kidney. Kidney HIF-2α directly controls the transcription and the production of erythropoietin (EPO), a protein that stimulates the production of red blood cells. Very simply put, the FG-4592 (roxadustat) tricks your body into thinking the oxygen levels are low. We could call it “the height of the tablet,” if we want to, as its effects on HIF-2A mimic some of the changes observed when a person rises to a great height.
Another great thing about this drug is that it is not a large complex of a peptide as erythropoietin (EPO) and its analogues, the main alloying agents in this class now. FG-4592 is a small molecule, with the added benefit is very stable and orally bioavailable. It may be given instead of tablets injection. This is likely to make it attractive to a larger number of athletes. EPO drugs had a reputation for pretty niched so far. They have not been widely adopted by athletes, except for the most competitive laps. They are difficult to use, potentially dangerous, and bear the discomfort and stigma injection. While we are not clear on the safety FG-4592 and other drugs like it, we see the potential for this class of drugs to be taken by a much wider body of athletes, considering that you just have to swallow the tablet.
But wait … The New York Times quoted the representative AstraZeneca Abigail Bozarth, as they say, “There’s no other drug like FG-4592.” Perhaps there is an accurate statement, if you view it with a chemical structure very strong point of view. In fact, FG-4592 is one of the many new PHD inhibitors under development, even currently in clinical evaluation for the treatment of anemia. Some other well-known agents include AKB-6548 Akebia, in BAY85-3934 from Bayer, FG-2216 and it (fg 4592 doping) developed by FibroGen and GSK1278863 company GlaxoSmithKline. There are actually 22 trials was recorded in the United States for PHD inhibitors until now. I’ve included a quick chart that highlights their plan for review, taken from a recent article in the journal Stem Cells Translational Medicine.
It is still too early to draw conclusions about the FG-4592, or PHD inhibitors in general. There appears to be ample evidence suggesting these agents work to support the production of red cells, as in theory. But then again, none of these drugs has not yet been fully evaluated for safety. Until now, no toxic effects were seen. There is still a lot we do not know about them, however, and, of course, they can be optimally used. We must remember that erythropoiesis is potentially dangerous to tinker with the system. This can be a fine line between the increase in hematocrit (red cell density) to such an extent that improves performance, and one that is largely endangers the individual with thickened blood and the risk of heart attack or stroke. Potential for lightweight “the EPO pill” causes a lot of issues and problems. At this point, I think it’s better not to experiment with FG-4592 the black market. We will probably learn a lot more about this in the coming months and years. At the same time, it’s really an interesting topic. Of course, I try to follow her.