Ro 08-2750 is a competitive inhibitor of Musashi (MSI)–RNA interactions, with an IC50 value of 2.7±0.4µM [1]. Ro 08-2750-mediated inhibition of MSI can reduce aldosterone production, with an IC50 value of 1.50± 0.154µM[2]. Ro 08-2750 has been widely applied in disease models to regulate the expression and activity of nerve growth factors[3].
In vitro, Ro 08-2750 treatment for 96 hours significantly inhibited the viability of MDA-MB-468 cells, SUM149PT cells, UIVC-IDC-2 cells and UIVC-IDC-4 cells with IC50 values of 6.3µM, 12.8µM, 12.8µM, and 14µM, respectively[4]. Treatment with 10μM Ro 08-2750 for 7 days significantly inhibited the expression of osteogenic-related genes and protein markers in dental pulp stem cells[5]. The 2nM Ro 08-2750 treatment for 24 hours on MDA-MB-231 cells significantly inhibited the expression of p75NTR protein[6].
In vivo, Ro 08-2750 treatment via intraperitoneal injection (13.75mg/kg) once every two days for two consecutive weeks significantly inhibited the growth of xenograft tumors in the cervical cancer mouse model and significantly increased the levels of p-LATS1 and p-YAP proteins in the tumor tissues[7]. By intraperitoneal injection at a dose of 7.0mg/kg twice a week for 21 days, Ro 08-2750 significantly inhibited the tumor burden in a chronic lymphocytic leukemia (CLL) mouse model[8].
References:
[1] Minuesa G, Albanese S K, Xie W, et al. Small-molecule targeting of MUSASHI RNA-binding activity in acute myeloid leukemia[J]. Nature communications, 2019, 10(1): 2691.
[2] Walters K, Sajek M P, Murphy E, et al. Small-molecule Ro-08-2750 interacts with many RNA-binding proteins and elicits MUSASHI2-independent phenotypes[J]. Rna, 2023, 29(10): 1458-1470.
[3] Kao T H, Peng Y J, Salter D M, et al. Nerve growth factor increases MMP9 activity in annulus fibrosus cells by upregulating lipocalin 2 expression[J]. European Spine Journal, 2015, 24(9): 1959-1968.
[4] Brücksken K A, Sicking M, Korsching E, et al. Musashi inhibitor Ro 08–2750 attenuates triple-negative breast cancer cell proliferation and migration and acts as a novel chemo-and radiosensitizer[J]. Biomedicine & pharmacotherapy, 2025, 186: 118002.
[5] Cheng C, Tang S, Cui S, et al. Nerve growth factor promote osteogenic differentiation of dental pulp stem cells through MEK/ERK signalling pathways[J]. Journal of Cellular and Molecular Medicine, 2024, 28(4): e18143.
[6] Chakravarthy R, Mnich K, Gorman A M. Nerve growth factor (NGF)-mediated regulation of p75NTR expression contributes to chemotherapeutic resistance in triple negative breast cancer cells[J]. Biochemical and biophysical research communications, 2016, 478(4): 1541-1547.
[7] Wang L, Li J, Wang R, et al. NGF signaling interacts with the Hippo/YAP pathway to regulate cervical cancer progression[J]. Frontiers in oncology, 2021, 11: 688794.
[8] Palacios F, Yan X J, Ferrer G, et al. Musashi 2 influences chronic lymphocytic leukemia cell survival and growth making it a potential therapeutic target[J]. Leukemia, 2021, 35(4): 1037-1052.
Ro 08-2750是一种竞争性Musashi (MSI)-RNA相互作用抑制剂，IC50值为2.7±0.4µM[1]。Ro 08-2750通过抑制MSI功能可降低醛固酮生成，IC50值为1.50±0.154µM[2]。Ro 08-2750已广泛应用于疾病模型中调控神经生长因子的表达与活性[3]。
在体外，Ro 08-2750处理96小时能显著抑制MDA-MB-468、SUM149PT、UIVC-IDC-2和UIVC-IDC-4细胞活力，IC50值分别为6.3µM、12.8µM、12.8µM和14µM[4]。使用10μM的Ro 08-2750处理牙髓干细胞7天，可显著抑制成骨相关基因和蛋白标志物的表达[5]。用2nM的Ro 08-2750处理MDA-MB-231细胞24小时，能显著抑制p75NTR蛋白表达[6]。
在体内，Ro 08-2750通过腹腔注射（13.75mg/kg）每两天一次，连续进行两周，可显著抑制宫颈癌小鼠模型移植瘤的生长，并提高肿瘤组织中p-LATS1和p-YAP蛋白水平[7]。通过每周两次腹腔注射7.0mg/kg剂量的Ro 08-2750连续21天，能显著减轻慢性淋巴细胞白血病(CLL)小鼠模型的肿瘤负荷[8]。