| Description | NE 10790 (3-PEHPC) is a phosphonocarboxylate analogue of the potent bisphosphonate risedronate and is a weak anti-resorptive agent. Although NE10790 was a poor inhibitor of FPP synthase |
| In vitro | NE 10790在J774巨噬细胞和破骨细胞中抑制了分子质量大约22-26 kDa蛋白的前列化，而这些蛋白的前列化不受肽类模拟物抑制剂（如farnesyl transferase的FTI-277或geranylgeranyl transferase I的GGTI-298）的影响。这些22-26 kDa的蛋白通过在J774细胞中标记[(3)H]geranylgeraniol被证实为geranylgeranylated。此外，NE10790抑制了[(14)C]mevalonic酸并入Rab6，但并未影响H-Ras或Rap1蛋白的并入，这些蛋白分别由FTase和GGTase I修改。这些数据表明，NE10790在完整细胞中选择性地防止了Rab的前列化。相应地，NE10790抑制了体外重组Rab GGTase的活性，但未影响重组FTase或GGTase I的活性。因此，NE10790似乎是首个被确认的Rab GGTase的特异性抑制剂。与risedronate相比，NE10790在体外抑制骨吸收，但对破骨细胞数量或极化破骨细胞的F-actin“环”结构没有明显影响。然而，NE10790确实改变了破骨细胞的形态，导致大型细胞内空泡的形成和基底侧膜向形成无微绒毛的大型“穹顶”结构的凸出。因此，NE10790的抗吸收活性可能是由于干扰破骨细胞中Rab依赖的细胞内膜运输[1]。 |
| Synonyms | 3-PEHPC |
| molecular weight | 247.14 |
| Molecular formula | C8H10NO6P |
| CAS | 152831-36-2 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | H2O: 5 mg/mL (20.23 mM), when pH is adjusted to 6 with NaOH. Sonication is recommended. DMSO: < 1 mg/mL (insoluble） |
| References | 1. Coxon FP, et al. Identification of a novel phosphonocarboxylate inhibitor of Rab geranylgeranyl transferase that specifically prevents Rab prenylation in osteoclasts and macrophages. J Biol Chem. 2001 Dec 21;276(51):48213-22. 2. Hald A , Hansen R R , Thomsen M W , et al. Cancer-induced bone loss and associated pain-related behavior is reduced by risedronate but not its phosphonocarboxylate analog NE-10790[J]. 2009, 125(5):1177-1185. |