OAC3

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Background

OAC3 is identified as an activator of octamer-binding transcription factor 4. Octamer-binding transcription factor 4 (Oct4), a key regulator of embryonic stem cell (ESC) pluripotency, is cirtical to the reprogramming process.In vitro: OAC3 was shown to be able to activate both Oct4 and Nanog reporters to a similar extent as OAC1, which was its analog with greatest activating effects on both Oct4 and Nanog promoter-driven luciferase reporter genes. It was also found that both OAC1 and OAC3 could considerably enhance the 4F-induced reprogramming efficiency. Furthermore, OAC1 and OAC3 enhanced reprogramming efficiency four-fold, up to as high as 2.75%, and also accelerated the appearance of iPSC colonies 3 to 4 d when used in combination with the four reprogramming factors, which were Oct4, Sox2, Klf4, and c-Myc [1]. In vivo: In animal to test the in vivo pluripotency of the 4F+OAC2-induced iPSCs, which was another OAC3 analog, the 4F+OAC2-iPSCs were transplanted the into immunodeficient Nude mice. Results showed that 4 to 6 weeks after transplantation, 4F+OAC2-iPSCs generated typical teratomas containing derivative of three germ layers effectively, such as epidermis of ectoderm, blood of mesoderm, and intestinal epithelia of endoderm [1]. Clinical trial: Up to now, OAC3 is still in the preclinical development stage.

Reference:[1] Li W,Tian E,Chen ZX,Sun G,Ye P,Yang S,Lu D,Xie J,Ho TV,Tsark WM,Wang C,Horne DA,Riggs AD,Yip ML,Shi Y. Identification of Oct4-activating compounds that enhance reprogramming efficiency. Proc Natl Acad Sci U S A.2012 Dec 18;109(51):20853-8.