product name STF-118804
Description: STF-118804 is a highly potent and specific NAMPT inhibitor (nicotinamide phosphoribosyl transferase inhibitor), which improves survival in an orthotopic xenotransplant model of high-risk acute lymphoblastic leukemia, and targets leukemia stem cells. In B-ALL cell lines, STF-118804 reduced the viability with high potency. In leukemic samples from pediatric acute lymphoblastic leukemia (ALL) patients, STF-118804 reduced the viability with IC50 values of 3.1-32.3 nM.
References: Leukemia. 2015 Feb;29(2):474-82; J Exp Med. 2014 Apr 7;211(4):605-12.
461.53
Formula
C25H23N3O4S
CAS No.
894187-61-2
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 61 mg/mL (132.16 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: STF-118804 reduces the viability of B-ALL cell lines containing MLL chromosomal translations, with IC50 values in the low nanomolar range. In addition, leukemic samples from five pediatric ALL patients are also sensitive to STF-118804 in the low nanomolar range. STF-118804 induces leukemia MV411 cell apoptosis without antecedent cell cycle arrest. Kinase Assay: The enzymatic activities of NAMPT and NMNAT are measured using in vitro kits and using the Two-Step Method per manufacturer’s instructions. Compounds, NAMPT and/or NMNAT enzymes, and their substrates are mixed and incubated at 30°C for 1 hour. Reagents for the indicator reaction (Wst-1) are then added, and absorbance is read at 450 nm every 5 min at 30°C on a Tecan Infinite M100 multimode plate reader. Cell Assay: Human cell lines or lineage negative cord blood cells were seeded into 96-well plates (6×105 cells per milliliter). Compounds are added in increasing concentrations, and cells are incubated at 37°C/5% CO2 for 72 hours. To detect viability, CellTiter-Blue reagent is added at 1:10 dilution, and plates are incubated for 4 hours at 37°C/5% CO2 prior to reading on a Flexstation II 384 or a Synergy H1 reader at an excitation of 555 nm and emission detection of 590 nm. Cell viability is also measured by CellTiter-Fluor. The cell-permeable fluorogenic peptide substrate GF-AFC reagent is added at 1:2 dilution, and plates are incubated for 30 min at 37°C/5% CO2 prior to reading on a Synergy H1 reader at an excitation of 380 nm and emission detection of 505 nm. Cord blood cells are enumerated on a hemocytometer, and cell viability is assessed with trypan blue exclusion dye. Inhibitory concentration (IC50) is calculated using Prism software. Primary patient samples are plated in 96-well plates and treated with increasing concentrations of STF-118804 for 48 hours at 37°C in 5% CO2. WST-1 reagent is added to the culture medium (1:10 dilution), and absorbance is measured at 450 nm using a Bio-Rad model 680 microplate reader. All assays are performed in triplicate. IC50 is calculated using CalcuSyn version 2.0 software. |
|---|---|
| In Vivo | STF-118804 (25 mg/kg twice daily, s.c.) improves survival in an orthotopic xenotransplant model of high-risk acute lymphoblastic leukemia, and effectively depletes leukemia-initiating cells. |
| Animal model | Orthotopic xenograft model of ALL transplanted with MV411 cells |
| Formulation & Dosage | Formulated in 20% [w/v] [2-hydroxypropyl]-γ-cyclodextrin/5% [v/v] DMSO, and diluted in PBS; 25 mg/kg; s.c. administration |
| References | Leukemia. 2015 Feb;29(2):474-82; J Exp Med. 2014 Apr 7;211(4):605-12. |
