Background:

IC50: N/A

16,16-Dimethyl Prostaglandin E2 (dmPGE2) is the synthetic derivative ofprostaglandin E2. Since prostaglandin E has immunosuppressive effects and potentially could lessen the toxic effects of cyclosporine, prostaglandin E usage in the setting of allotransplantation has been suggested both clinically and experimentally.

In vitro: DmPGE2 was reported to cause an increase in runx11/cmyb1 HSCs, while HSCs were inhibited by indomethacin treatment in 90% of embryos. Moreover, dmPGE2 had minimal effects on the vasculature, while indomethacin altered the intersomitic vessels slightly. Imaged by confocal microscopy, red-labelled HSCs and endothelium embryos showed significantly increased HSCs following dmPGE2 exposure [1].

In vivo: In a heterotopic model of rat allograft rejection, dmPGE2 could delay the rejection onset, but all animals developed severe rejection and died subsequently. Treatment of animals with low-dose CsA in combination with dmPGE2 led to a delay in the onset as well as a reduction in the intensity of allograft rejection. In addition, a statistical relationship between procoagulant activity levels and the time of onset of rejection was observed [1].

Clinical trial: N/A

参考文献:
[1] North TE,Goessling W,Walkley CR,Lengerke C,Kopani KR,Lord AM,Weber GJ,Bowman TV,Jang IH,Grosser T,Fitzgerald GA,Daley GQ,Orkin SH,Zon LI.  Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis. Nature.2007 Jun 21;447(7147):1007-11.
[2] Koh IH,Kim PC,Chung SW,Waddell T,Wong PY,Gorczynski R,Levy GA,Cohen Z.  The effects of 16, 16 dimethyl prostaglandin E2 therapy alone and in combination with low-dose cyclosporine on rat small intestinal transplantation. Transplantation.1992 Oct;54(4):592-8.