Nampt-IN-1

Additional information:
Nampt-IN-1 (LSN3154567) is a potent and selective NAMPT inhibitor. Nampt-IN-1 inhibits purified NAMPT with an IC50 of 3.1 nM.|Product information|CAS Number: 1698878-14-6|Molecular Weight: 419.49|Formula: C20H25N3O5S|Chemical Name: 2-hydroxy-2-methyl-N-{2-[2-(pyridin-3-yloxy)acetyl]-1,2,3,4-tetrahydroisoquinolin-6-yl}propane-1-sulfonamide|Smiles: CC(C)(O)CS(=O)(=O)NC1=CC2CCN(CC=2C=C1)C(=O)COC1C=NC=CC=1|InChiKey: QHHSCLARESIWBH-UHFFFAOYSA-N|InChi: InChI=1S/C20H25N3O5S/c1-20(2,25)14-29(26,27)22-17-6-5-16-12-23(9-7-15(16)10-17)19(24)13-28-18-4-3-8-21-11-18/h3-6,8,10-11,22,25H,7,9,12-14H2,1-2H3|Technical Data|Appearance: Solid Power|Purity: ≥98% (or refer to the Certificate of Analysis)|Solubility: DMSO : 250 mg/mL (595.{{Nomegestrol} MedChemExpress|{Nomegestrol} Vitamin D Related/Nuclear Receptor|{Nomegestrol} Purity & Documentation|{Nomegestrol} Data Sheet|{Nomegestrol} manufacturer|{Nomegestrol} Autophagy} 96 mM; Need ultrasonic).|Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis|Storage Condition: Dry, dark and -20 oC for 1 year or refer to the Certificate of Analysis.|Shelf Life: ≥12 months if stored properly.|Stock Solution Storage: 0 – 4 oC for 1 month or refer to the Certificate of Analysis.|Drug Formulation: To be determined|HS Tariff Code: 382200|How to use|In Vitro:|To assess its selectivity, specificity, and effects on cellular NAD+ levels, LSN3154567 is characterized in various biochemical and cellular assays.{{Amiloride hydrochloride dihydrate} MedChemExpress|{Amiloride hydrochloride dihydrate} Inhibitor|{Amiloride hydrochloride dihydrate} TGF-beta/Smad|{Amiloride hydrochloride dihydrate} Protocol|{Amiloride hydrochloride dihydrate} In Vitro|{Amiloride hydrochloride dihydrate} supplier} 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). 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).PMID:31916914 LSN3154567 exhibits a potent antiproliferative activity against many cell lines in the absence of NA.|In Vivo:|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 TED50 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.|Products are for research use only. Not for human use.|