Conclusions

The interaction of a ligand with its cell surface receptor results in a complex series of engagement events that brings together multiple proteins in a specific three-dimensional arrangement. This interaction, and the resulting conformational change it triggers, generates a cascade of intracellular events that lead to the physiologic consequences unique to each growth factor. Given this complexity, it was perhaps surprising that both small molecules and peptides can mimic the effects of a growth factor. Recent studies, however, have clearly established this to be the case. Whether any of these molecules, or subsequent generations of them, will display the safety and specificity of the recombinant counterparts to the native proteins remains to be determined.

Fig. 7. Platelet responses in BALB/c mice to rHuTPO or GW395058. Average platelet counts in mouse blood samples are shown. Blood samples were obtained from BALB/c mice (n = 5/group; 3 dose cycles/group) that were receiving subcutaneous doses on d 1, 43, and 85 (arrows) of rHuTPO at 50 pg/kg, QD X 5/cycle (closed squares), GW395058 at 25 pg/kg, single dose/cycle (closed triangles), or vehicle (closed circles). (Reproduced with permission from ref. 48. © AlphaMed Press 1066-5099.)

Fig. 7. Platelet responses in BALB/c mice to rHuTPO or GW395058. Average platelet counts in mouse blood samples are shown. Blood samples were obtained from BALB/c mice (n = 5/group; 3 dose cycles/group) that were receiving subcutaneous doses on d 1, 43, and 85 (arrows) of rHuTPO at 50 pg/kg, QD X 5/cycle (closed squares), GW395058 at 25 pg/kg, single dose/cycle (closed triangles), or vehicle (closed circles). (Reproduced with permission from ref. 48. © AlphaMed Press 1066-5099.)

Safety and specificity are critical characteristics of candidate therapeutics, and the established profiles of protein therapeutics in these areas have set the bar very high.

It is also noteworthy that the area of protein therapeutics itself is evolving. The notion that a physiologic protein represents the ultimate in evolutionary development has been dispelled, at least from a therapeutic perspective. Site-directed mutagenesis of DNA encoding human EPO has resulted in a new protein, darbepoetin alfa, which not only has enhanced biologic properties but also retains the safety and specificity profiles of rHuEPO (51). Having demonstrated that proteins themselves can be improved, further advances are likely to occur that will make it more difficult for a small molecule to enter the therapeutic arena. However, the potential advantages offered in terms of oral delivery and cost of manufacture will ensure that small-molecule mimetics will continue to be an active area of on-going research.

Was this article helpful?

0 0
10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook


Post a comment