Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài: S110, a novel decitabine dinucleotide, increases fetal hemoglobin levels in baboons (P. anubis) | Lavelle et al. Journal of Translational Medicine 2010 8 92 http content 8 1 92 RESEARCH JOURNAL OF TRANSLATIONAL MEDICINE Open Access S110 a novel decitabine dinucleotide increases fetal hemoglobin levels in baboons P. anubis Donald Lavelle Yogen Saunthararajah Kestis Vaitkus Mahipal Singh 2 Virryan Banzon D-jri-f- Dhi2ci tnric 24 niDoHIz r4 IZ nolz I4 Rosỉrcc4 Qhi4 If ilr toc4 rasiL rhiasivongsva sanjeev nedkai saiaui Kanekal David Beaiss Cuongue Shi nogei Inloes Joseph DeSimone1 2 Abstract Background S110 is a novel dinucleoside analog that could have advantages over existing DNA methyltransferase DNMT inhibitors such as decitabine. A potential therapeutic role for S110 is to increase fetal hemoglobin HbF levels to treat b-hemoglobinopathies. In these experiments the effect of S110 on HbF levels in baboons and its ability to reduce DNA methylation of the y-globin gene promoter in vivo were evaluated. Methods The effect of S110 on HbF and y-globin promoter DNA methylation was examined in cultured human erythroid progenitors and in vivo in the baboon pre-clinical model. S110 pharmacokinetics was also examined in the baboon model. Results S110 increased HbF and reduced DNA methylation of the y-globin promoter in human erythroid progenitors and in baboons when administered subcutaneously. rharmacokinetic analysis was consistent with rapid conversion of S110 into the deoxycytosine analog decitabine that binds and depletes DNA. Conclusion S110 is rapidly converted into decitabine hypomethylates DNA and induces HbF in cultured human erythroid progenitors and the baboon pre-clinical model. Background Increased fetal hemoglobin levels are beneficial to patients with sickle cell disease and b-thalassemia. Patients with sickle cell disease with increased fetal hemoglobin levels have less pain crises 1 and longer life spans 2 . Therefore pharmacological agents that can elevate fetal hemoglobin have great potential as .
