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号:1698878-14-6
- 英文名:Nampt-IN-1
- 中文名: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
- CBNumber:CB53048664
- 分子式:C20H25N3O5S
- 分子量:419.49
- MOL File:1698878-14-6.mol
- 沸点 :659.9±65.0 °C(Predicted)
- 密度 :1.363±0.06 g/cm3(Predicted)
- 储存条件 :2-8°C
- 溶解度 :DMSO: Soluble
- 形态 :powder
- 酸度系数(pKa) :8.67±0.20(Predicted)
- 颜色 :white to beige
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、用途与生产工艺
- 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。
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靶点
IC50: 3.1 nM (NAMPT), 0.84 μM (CSF1R)
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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.
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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.
- 更新日期:2024/04/30
- 产品编号:HY-12971
- 产品名称:Nampt-IN-1
- CAS编号:
- 包装:1 mg
- 价格:380元
- 更新日期:2024/04/30
- 产品编号:HY-12971
- 产品名称: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 Nampt-IN-1
- CAS编号:1698878-14-6
- 包装:5mg
- 价格:950元
- 公司名称:Musechem
- 联系电话:+1-800-259-7612
- 电子邮件:info@musechem.com
- 国家:美国
- 产品数:4662
- 优势度:60
- 公司名称:Aladdin Scientific
- 联系电话:+1-+1(833)-552-7181
- 电子邮件:sales@aladdinsci.com
- 国家:美国
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- 公司名称:TargetMol Chemicals Inc.
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- 电子邮件:support@targetmol.com
- 国家:美国
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- 公司名称:BOC Sciences
- 联系电话: 16314854226
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- 联系电话:--
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- 公司名称:United States Biological Inc.
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- 公司名称:MedChemExpress
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