NE 10790

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

NE 10790 是强效双膦酸盐利塞膦酸盐的膦酰基羧酸盐类似物，是一种弱抗再吸收剂。

NE 10790 is a phosphonocarboxylate analogue of the potent bisphosphonate risedronate and is a weak anti-resorptive agent. Although NE10790 was a poor inhibitor of FPP synthaseNE 10790 did inhibit prenylation in J774 macrophages and osteoclasts, but only of proteins of molecular mass approximately 22-26 kDa, the prenylation of which was not affected by peptidomimetic inhibitors of either farnesyl transferase (FTI-277) or geranylgeranyl transferase I (GGTI-298).?These 22-26-kDa proteins were shown to be geranylgeranylated by labelling J774 cells with [(3)H]geranylgeraniol.?Furthermore, NE10790 inhibited incorporation of [(14)C]mevalonic acid into Rab6, but not into H-Ras or Rap1, proteins that are modified by FTase and GGTase I, respectively.?These data demonstrate that NE10790 selectively prevents Rab prenylation in intact cells.?In accord, NE10790 inhibited the activity of recombinant Rab GGTase in vitro, but did not affect the activity of recombinant FTase or GGTase I. NE10790 therefore appears to be the first specific inhibitor of Rab GGTase to be identified.?In contrast to risedronate, NE10790 inhibited bone resorption in vitro without markedly affecting osteoclast number or the F-actin "ring" structure in polarized osteoclasts.?However, NE10790 did alter osteoclast morphology, causing the formation of large intracellular vacuoles and protrusion of the basolateral membrane into large, "domed" structures that lacked microvilli.?The anti-resorptive activity of NE10790 is thus likely due to disruption of Rab-dependent intracellular membrane trafficking in osteoclasts.

NE 10790 inhibits incorporation of [14C]mevalonic acid into Rab6, but not into H-Ras or Rap1, proteins that are modified by FTase and GGTase I, respectively. NE 10790 reduces viability in J774 cells. NE 10790 prevents prenylation of 22-26-kDa proteins that are not modified by FTase or GGTase I.

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3-PEHPC

Others

Other Targets

FPP synthase

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152831-36-2

247.14

C8H10NO6P

>98% (HPLC)

H2O:5 mg/mL (20.23 mM; ultrasonic and adjust pH to 6 with NaOH)

OC(=O)C(O)(CC1=CN=CC=C1)P(O)(O)=O

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(-20℃)

With Ice Pack

≥ 2 years