RG 108 is a potent DNA methyltransferase inhibitor, with an IC50 value of 115nM[1]. By targeting DNA methyltransferases, RG 108 significantly reduced the hypermethylation levels of GSTP1, APC, and RAR-β2 promoters in prostate cancer cells, affecting cell cycle progression[2]. RG 108 has been widely used to increase the reprogramming efficiency of induced pluripotent stem cells (iPSCs) and improve blastocyst formation[3].
In vitro, RG 108 treatment for 12h significantly inhibited the proliferation of Eca-109 and TE-1 cells with IC50 values of 70µM and 75µM, respectively[4]. Treatment with 50μM RG 108 for 3 days increased the expression of NANOG, OCT4, and CD105 in human bone marrow mesenchymal stem cells (hBMSCs), accompanied by a significant reduction in the transcriptional levels of DNMTs[5]. Treatment with 100μM RG 108 for 5 days reversed the senescence phenotype of human periodontal ligament stem cells (hPDLSCs) and stimulated adipogenesis of pPDLSCs[6].
In vivo, RG 108 treatment via intraperitoneal injection at a dose of 20mg/kg/day for 3 days significantly attenuated cisplatin-induced acute kidney injury in mice, resulting in reduced tubular dilatation and glycogen deposition[7]. A single dose of RG 108 (10mg/kg) injected intraperitoneally 2 hours before noise exposure can improve noise-induced hearing loss, reduce hair cell damage, and auditory synapse loss in mice[8].
References:
[1] Brueckner B, Garcia Boy R, Siedlecki P, et al. Epigenetic reactivation of tumor suppressor genes by a novel small-molecule inhibitor of human DNA methyltransferases[J]. Cancer research, 2005, 65(14): 6305-6311.
[2] Graça I, J. Sousa E, Baptista T, et al. Anti-tumoral effect of the non-nucleoside DNMT inhibitor RG108 in human prostate cancer cells[J]. Current pharmaceutical design, 2014, 20(11): 1803-1811.
[3] Wu C, Zhang D, Zhang S, et al. Optimizing treatment of DNA methyltransferase inhibitor RG108 on porcine fibroblasts for somatic cell nuclear transfer[J]. Reproduction in Domestic Animals, 2019, 54(12): 1604-1611.
[4] Ou Y, Zhang Q, Tang Y, et al. DNA methylation enzyme inhibitor RG108 suppresses the radioresistance of esophageal cancer[J]. Oncology Reports, 2018, 39(3): 993-1002.
[5] Assis R I F, Wiench M, Silverio K G, et al. RG108 increases NANOG and OCT4 in bone marrow-derived mesenchymal cells through global changes in DNA modifications and epigenetic activation[J]. PLoS One, 2018, 13(12): e0207873.
[6] Roato I, Baima G, Orrico C, et al. Senescent markers expressed by periodontal ligament-derived stem cells (PDLSCs) harvested from patients with periodontitis can Be rejuvenated by RG108[J]. Biomedicines, 2023, 11(9): 2535.
[7] Kong F, Liu H, Xu T, et al. RG108 attenuates acute kidney injury by inhibiting P38 MAPK/FOS and JNK/JUN pathways[J]. International Immunopharmacology, 2024, 142: 113077.
[8] Zheng Z, Zeng S, Liu C, et al. The DNA methylation inhibitor RG108 protects against noise-induced hearing loss[J]. Cell Biology and Toxicology, 2021, 37(5): 751-771.
RG 108是一种强效的DNA甲基转移酶抑制剂，IC50值为115nM[1]。通过靶向DNA甲基转移酶，RG 108显著降低了前列腺癌细胞中GSTP1、APC和RAR-β2启动子的高甲基化水平，从而影响细胞周期进程[2]。RG 108已广泛用于提高诱导多能干细胞（iPSCs）的重编程效率和改善囊胚形成[3]。
在体外，RG 108处理12小时显著抑制了Eca-109和TE-1细胞的增殖，IC50值分别为70µM和75µM[4]。用50μM的RG 108处理3天增加了人骨髓间充质干细胞（hBMSCs）中NANOG、OCT4和CD105的表达，同时伴随着DNMTs转录水平的显著降低[5]。用100μM的RG 108处理5天逆转了人牙周膜干细胞（hPDLSCs）的衰老表型，并刺激了hPDLSC的脂肪形成[6]。
在体内，以20mg/kg/day的剂量腹腔注射RG 108连续3天显著减轻了顺铂诱导的小鼠急性肾损伤，导致肾小管扩张和糖原沉积减少[7]。在噪声暴露前2小时单次腹腔注射RG 108（10mg/kg）可改善噪声诱导的小鼠听力损失，减少毛细胞损伤和听觉突触丢失[8]。