Nampt inhibition by (E)-Daporinad (FK866) leads to a significant reduction in NAD+ levels intracellularly, selectively killing multiple myeloma (MM) cells. The cell death induced by (E)-Daporinad is linked to the inhibition of Nampt activity, not its protein expression. MM cells, having higher baseline NAD+ levels compared to normal peripheral blood mononuclear cells (PBMCs), are more susceptible to (E)-Daporinad. Additionally, (E)-Daporinad neutralizes the survival benefits that the bone marrow microenvironment confers on MM cells[1]. (E)-Daporinad (FK866) inhibits the increase in intracellular calcium ([Ca2+].i) that is typically induced by various mitogens and decreases the calcium content of thapsigargin-responsive calcium stores in Jurkat cells and activated peripheral blood lymphocytes (PBLs). However, it does not affect the calcium content in Bcl2-overexpressing Jurkat cells[2]. The inhibition of NAMPT by (E)-Daporinad (FK866), or SIRT by nicotinamide, reduces cell proliferation and induces cell death in 293T cells. This effect involves the p53 acetylation pathway, highlighting a critical regulatory mechanism in cell survival and death[3].
体内研究
In vivo, (E)-Daporinad (FK866) administered at 30 mg/kg intraperitoneally reduces tumor burden in CB17-SCID mice. In these mice, tumor tissues show significant reductions in ERK phosphorylation and increased proteolytic cleavage of LC3, indicating both signaling inhibition and autophagic activity[1].
体外研究
Nampt inhibition by (E)-Daporinad (FK866) leads to a significant reduction in NAD+ levels intracellularly, selectively killing multiple myeloma (MM) cells. The cell death induced by (E)-Daporinad is linked to the inhibition of Nampt activity, not its protein expression. MM cells, having higher baseline NAD+ levels compared to normal peripheral blood mononuclear cells (PBMCs), are more susceptible to (E)-Daporinad. Additionally, (E)-Daporinad neutralizes the survival benefits that the bone marrow microenvironment confers on MM cells[1].
(E)-Daporinad (FK866) inhibits the increase in intracellular calcium ([Ca2+].i) that is typically induced by various mitogens and decreases the calcium content of thapsigargin-responsive calcium stores in Jurkat cells and activated peripheral blood lymphocytes (PBLs). However, it does not affect the calcium content in Bcl2-overexpressing Jurkat cells[2].
The inhibition of NAMPT by (E)-Daporinad (FK866), or SIRT by nicotinamide, reduces cell proliferation and induces cell death in 293T cells. This effect involves the p53 acetylation pathway, highlighting a critical regulatory mechanism in cell survival and death[3].
(E)-Daporinad 细胞研究
细胞系
浓度
检测类型
检测时间
活动说明
数据源
human A2780 cells
Proliferation assay
72 h
Antiproliferative activity against human A2780 cells after 72 hrs by sulforhodamine B assay, IC50=1 nM
24405419
human A431 cells
Cytotoxic assay
Cytotoxicity against human A431 cells by clonogenic assay, IC50=6.1 nM
24164086
human A549 cells
Cytotoxic assay
6 days
Cytotoxicity against human A549 cells after 6 days by SRB assay, IC50=0.16 μM
21330015
human HCT116 cells
Cytotoxic assay
72 h
Cytotoxicity against human HCT116 cells assessed as growth inhibition after 72 hrs by WST-1 assay, IC50=10.9 nM
Antiproliferative activity against human A2780 cells after 72 hrs by sulforhodamine B assay, IC50=1 nM
24405419
human A431 cells
Cytotoxic assay
Cytotoxicity against human A431 cells by clonogenic assay, IC50=6.1 nM
24164086
human A549 cells
Cytotoxic assay
6 days
Cytotoxicity against human A549 cells after 6 days by SRB assay, IC50=0.16 μM
21330015
human HCT116 cells
Cytotoxic assay
72 h
Cytotoxicity against human HCT116 cells assessed as growth inhibition after 72 hrs by WST-1 assay, IC50=10.9 nM
24164086
human HCT116 cells
Cytotoxic assay
6 days
Cytotoxicity against human HCT116 cells after 6 days by SRB assay, IC50=0.16 μM
21330015
human HepG2 cells
Function assay
1 h
Inhibition of NAMPT in human HepG2 cells using [14C]-nicotinamide/PRPP as substrate assessed as formation of [14C]-nicotinamide mononucleotide after 1 hr by liquid scintillation counting analysis, IC50=2.2 nM
24164086
human HT1080 cells
Cytotoxic assay
6 days
Cytotoxicity against human HT1080 cells after 6 days by SRB assay, IC50=0.16 μM
21330015
human K562 cells
Cytotoxic assay
96 h
Cytotoxicity against human K562 cells after 96 hrs by MTT assay, IC50=7.2 nM
23679915
human MCF7 cells
10 μM
Function assay
6 days
Antitumor activity against human MCF7 cells at 10 uM after 6 days by SRB assay, IC50=0.68 μM
21330015
human MCF-7 cells
Cytotoxic assay
72 h
Cytotoxicity against human MCF-7 cells assessed as growth inhibition after 72 hrs by WST-1 assay, IC50=7.4 nM
24164086
human NYH cells
Cytotoxic assay
3 weeks
Cytotoxicity against human NYH cells after 3 weeks by clonogenic survival assay, IC50=1.5 nM
23679915
human PC3 cells
Cytotoxic assay
Cytotoxicity against human PC3 cells by clonogenic assay, IC50=3.8 nM
24164086
human SH-SY5Y cells
Cytotoxic assay
Cytotoxicity against human SH-SY5Y cells assessed as reduction of total cellular NAD(P) level, IC50=0.5 nM
19961183
human SKOV3 cells
Cytotoxic assay
Cytotoxicity against human SKOV3 cells by clonogenic assay, IC50=211 nM
24164086
human SNU638 cells
Cytotoxic assay
6 days
Cytotoxicity against human SNU638 cells after 6 days by SRB assay, IC50=0.16 μM
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