کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1930676 | 1050523 | 2011 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Improvement of biological and pharmacokinetic features of human interleukin-11 by site-directed mutagenesis Improvement of biological and pharmacokinetic features of human interleukin-11 by site-directed mutagenesis](/preview/png/1930676.png)
Recombinant human interleukin-11 (rhIL-11) has been shown to increase platelet counts in animals and humans and is the only drug approved for its use in chemotherapy-induced thrombocytopenia (CIT). However, due to its serious side effects, its clinical use has been limited. The current work presents significantly improved efficacy of rhIL-11 via knowledge based re-designing process. The interleukin-11 mutein (mIL-11) was found to endure chemical and proteolytic stresses, while retaining the biological activity of rhIL-11. The improved efficacy of mIL-11 was evident after subcutaneous administration of mIL-11 and rhIL-11 in the rodent and primate models. More than three-fold increase in maximum plasma concentration (Cmax) and area-under-the curve (AUC) was observed. Furthermore, three-fold higher increase in the platelet counts was obtained after seven consecutive daily subcutaneous mIL-11 injections than that with rhIL-11. The mIL-11 demonstrated not only improved stability but also enhanced efficacy over the currently used rhIL-11 regimen, thereby suggesting less toxicity.
Research highlights
► Site-directed mutagenesis was introduced to human interleukin-11 to improve stability.
► The interleukin-11 mutein exhibited enhanced pharmacokinetic features and efficacy.
► The present work directs a possibility as a reinvestigated approach for chemotherapy-induced thrombocytopenia treatment.
Journal: Biochemical and Biophysical Research Communications - Volume 405, Issue 3, 18 February 2011, Pages 399–404