2-羟基-2-甲基-N-[1,2,3,4-四氢-2-[2-(3-吡啶基氧基)乙酰基]-6-异喹啉基]-1-丙烷磺酰胺 CAS#: 1698878-14-6

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2-羟基-2-甲基-N-[1,2,3,4-四氢-2-[2-(3-吡啶基氧基)乙酰基]-6-异喹啉基]-1-丙烷磺酰胺

生物活性靶点体外研究体内研究 用途与合成方法 MSDS 2-羟基-2-甲基-N-[1,2,3,4-四氢-2-[2-(3-吡啶基氧基)乙酰基]-6-异喹啉基]-1-丙烷磺酰胺价格(试剂级) 上下游产品信息

中文名称	2-羟基-2-甲基-N-[1,2,3,4-四氢-2-[2-(3-吡啶基氧基)乙酰基]-6-异喹啉基]-1-丙烷磺酰胺
中文同义词	2-羟基-2-甲基-N-[1,2,3,4-四氢-2-[2-(3-吡啶基氧基)乙酰基]-6-异喹啉基]-1-丙烷磺酰胺;NAMPT抑制剂(NAMPT-IN-1);化合物NAMPT-IN-1;2-羟基-2-甲基-N-[1,2,3,4-四氢-2-[2-(3-吡啶基氧基)乙酰基]-6-异喹啉基]-1-丙烷磺酰
英文名称	Nampt-IN-1
英文同义词	Nampt-IN-1;2-hydroxy-2-methyl-N-(2-(2-(pyridin-3-yloxy)acetyl)-1,2,3,4-tetrahydroisoquinolin-6-yl)propane-1-sulfonamide;2-Hydroxy-2-methyl-N-[1,2,3,4-tetrahydro-2-[2-(3-pyridinyloxy)acetyl]-6-isoquinolinyl]-1-propanesulfonamide;LSN3154567 (Nampt-IN-1);LSN3154567;2-hydroxy-2-methyl-N-[1,2,3,4-tetrahydro-2-[2-(3-pyridinyloxy)acetyl]-6-;LSN 3154567;LSN-3154567;LSN3154567;Nampt inhibitor 1
CAS号	1698878-14-6
分子式	C20H25N3O5S
分子量	419.49
EINECS号
相关类别	细胞生物学试剂
Mol文件	1698878-14-6.mol
结构式

2-羟基-2-甲基-N-[1,2,3,4-四氢-2-[2-(3-吡啶基氧基)乙酰基]-6-异喹啉基]-1-丙烷磺酰胺 性质

2-羟基-2-甲基-N-[1,2,3,4-四氢-2-[2-(3-吡啶基氧基)乙酰基]-6-异喹啉基]-1-丙烷磺酰胺 用途与合成方法

生物活性

Nampt-IN-1 (LSN3154567) 是一种有效的选择性 NAMPT 抑制剂。Nampt-IN-1 抑制纯化的 NAMPT，IC50 为 3.1 nM。

靶点

IC50: 3.1 nM (NAMPT), 0.84 μM (CSF1R)

体外研究

To assess its selectivity, specificity, and effects on cellular NAD     ⁺    levels, LSN3154567 is characterized in various biochemical and cellular assays. LSN3154567 inhibits purified NAMPT with an IC     ₅₀    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.: IC     ₅₀    ≥1 μM) against the kinases tested except CSF1R (IC     ₅₀    ≈0.84 μM). LSN3154567 exhibits a broad spectrum of anticancer activity. 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.

体内研究

Nampt-IN-1 (LSN3154567) exhibits good physical chemical properties that allow oral dosing. 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 TED     ₅₀    value of 2.0 mg/kg. To assess whether LSN3154567 causes retinopathy, rats are treated with LSN3154567 at 20, 40, and 80 mg/kg for 4 days. No apparent retinopathy is observed. The hematological toxicities are observed. When LSN3154567 is dosed at 20, 40, and 80 mg/kg, the plasma exposures obtained are 8,974, 18,061, and 38,327 M*h, respectively. Thus, LSN3154567 exhibits exposure multiples of respective 3-, 7-, and 14-fold over the exposure (2,701 M*h) required for robust efficacy (≈103%) without NA coadministration. 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. At the 1 and 2.5 mg/kg dose levels, the plasma exposures are determined to be 1,483 and 2,468 nM*h, respectively.

安全信息

MSDS信息

2-羟基-2-甲基-N-[1,2,3,4-四氢-2-[2-(3-吡啶基氧基)乙酰基]-6-异喹啉基]-1-丙烷磺酰胺 价格(试剂级)

2-羟基-2-甲基-N-[1,2,3,4-四氢-2-[2-(3-吡啶基氧基)乙酰基]-6-异喹啉基]-1-丙烷磺酰胺 上下游产品信息