| Description | IT-901 is an orally active and potent NF-κB subunit c-Rel inhibitor with an IC50 for NF-κB and c-Rel binding to DNA of 0.1 µM and 3 µM, respectively.IT-901 is a naphthalene thiobarbiturate derivative with antitumor activity and is used for the prevention and treatment of human lymphoma and myeloma. |
| In vitro | 在24小时内，以1、3、5 μM的浓度处理ABC和GCB DLBCL活跃细胞后，观察到它们的增殖下降。在3 μM浓度和24小时处理时间下，IT-901诱导了剂量依赖性的细胞活力下降；在4 μM IT-901处理48小时后，除HBL1外的所有测试细胞系中至少还有60%的细胞保持活力。6小时处理时，1、5、10 μM的浓度下，IT-901降低了原发性CLL细胞和细胞系中核和细胞质部分的p65和p50表达，并且减少了磷酸化和非磷酸化形式的抑制亚单位IκBα的表达。IT-901/GDM-12对c-Rel的IC50为2.9 μM，同时在5 μM浓度下有效阻断IL-2分泌。当IT-901浓度超过10 μM时，其毒性增加，可能诱发健康细胞的凋亡。IT-901在活化的B样（ABC）和生发中心B样（GCB）细胞系中抑制细胞生长，IC50值在3 μM至4 μM之间。 |
| In vivo | IT-901每隔一天腹腔注射（IP）24 mg/kg，连续两周，对急性移植物抗宿主病（GVHD）具有有效治疗作用[2]。IT-901通过腹腔注射（IP）12至20 mg/kgIT-901，可以提高药物动力学（PK）特性，增加半衰期（T1/2）和最大血浆浓度（Cmax）[2]。 |
| Target activity | NF-κB:0.1 μM, c-Rel:2.9μM, GCB:4 μ M |
| molecular weight | 342.37 |
| Molecular formula | C17H14N2O4S |
| CAS | 1584121-99-2 |
| Storage | |Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 10 mg/mL (29.21 mM), Sonication is recommended. |
| References | 1. Vaisitti T, et al. Targeting metabolism and survival in chronic lymphocytic leukemia and Richter syndrome cellsby a novel NF-κB inhibitor. Haematologica. 2017 Nov;102(11):1878-1889. 2. Shono Y, et al. Characterization of a c-Rel Inhibitor That Mediates Anticancer Properties in HematologicMalignancies by Blocking NF-κB-Controlled Oxidative Stress Responses. Cancer Res. 2016 Jan 15;76(2):377-89. |