| 名称 | Nampt-IN-1 |
| 描述 | Nampt-IN-1 (LSN3154567) (LSN3154567) is a potent and selective NAMPT inhibitor. Nampt-IN-1 inhibits purified NAMPT with an IC50 of 3.1 nM. |
| 细胞实验 | The cell lines used as following: A2780 and KM-12, KMS-11 and MKN-74, OPM-2 and Kelly; and all other cancer cells. Cells are seeded in 96-well plates, cultured overnight, and treated with LSN3154567 (0.03 to 1,000 nM)±NA (10 μM) in duplicate at 37°C in 5% CO2 for 72 hours. Staurosporine (10 μM) is used as positive control. Cell viability is determined by a CytoTox-Glo Cytotoxicity assay kit. |
| 动物实验 | Male CD-1 mice are dosed with LSN3154567 at 2 mg/kg intravenously in 20% Captisol (w/v), 25 mmol/L NaPO4, pH 2, q.s. formulation or 2 mg/kg orally in the same vehicle in a cross over design with 3-d wash period in between two arms. Blood samples are obtained through retro orbital at 0, 0.08 (IV only), 0.25, 0.75, 2, 4, 8, and 24 hours and frozen until analysis. For exposure analysis, blood samples (≈20 μL) are obtained through tail clipping at 0.5, 1, 2, 4, 8, and 24 hours. The samples are collected into EDTA-coated capillary tubes and spotted onto Whatman DMPK-C DBS collection cards. |
| 体外活性 | LSN3154567 inhibits purified NAMPT with an IC50 of 3.1 nM. When tested against a panel of human kinases (>100; CEREP Kinase panel), it does not exhibit any significant activity (i.e.: IC50≥1 μM) against the kinases tested except CSF1R (IC50≈0.84 μM). To assess its anticancer activity, LSN3154567 is tested against a number of different types of cancer cell lines cultured in the absence or presence of nicotinic acid (NA) (10 μM). LSN3154567 exhibits a potent antiproliferative activity against many cell lines in the absence of NA. |
| 体内活性 | When dosed orally with 2 mg/kg in mice, it has an exposure of 195 nM*hour in the plasma with a peak concentration of 57 nM (at 0.25 hour) and an oral bioavailability of 39%. When dosed intravenously with 2 mg/kg, it has a hepatic clearance of 158.73 mL/min/kg and a volume of distribution at 7.1 L/kg. The half-life of terminal elimination is estimated to be 2.76 hours. LSN3154567 exhibits a dose-dependent inhibition of NAD+ formation with estimated TED50 value of 2.0 mg/kg. Dogs are treated with LSN3154567 at 1 and 2.5 mg/kg. At these dose levels, the retinal toxicity is observed. Degeneration of the outer nuclear layer occurred in all four animals, but is less pronounced in the animals treated with 1 mg/kg. |
| 存储条件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | 10% DMSO+40% PEG300+5% Tween 80+45% Saline : 2 mg/mL (4.77 mM), Sonication is recommended.
DMSO : 55 mg/mL (131.11 mM), Sonication is recommended.
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| 关键字 | Visfatin | Pre-B cell colony enhancing factor | PBEF | Nicotinamide phosphoribosyl transferase | Nampt-IN-1 | NamptIN1 | Nampt IN 1 | NAMPT | LSN-3154567 | LSN 3154567 | Inhibitor | inhibit | CSF-1R | CSF1R | cFms |
| 相关产品 | Cerdulatinib hydrochloride | GW786034B | Sotuletinib | PLX647 | Masitinib | GW2580 | Tandutinib | c-Fms-IN-13 | Pexidartinib | PLX5622 | Nampt activator-1 | (E)-Daporinad |
| 相关库 | 抑制剂库 | 肿瘤免疫治疗小分子化合物库 | 经典已知活性库 | 已知活性化合物库 | 细胞因子抑制剂库 | 代谢化合物库 | NO PAINS 化合物库 | 糖代谢化合物库 | 膜蛋白靶向化合物库 | 酪氨酸激酶分子库 | 抗代谢疾病化合物库 |