Sphingosine is an intermediate of sphingolipids that can be rapidly phosphorylated by sphingosine kinase (SK1 and SK2) to produce sphingosine 1-phosphate, which is a mitogenic compound. ABC294640 is a selective inhibitor of SK2 with a Ki value of 9.8 μM. ABC294640 dose-dependently inhibited recombinant human SK2 with an IC50 value of 60μM, while the activity of SK1 was not affected by ABC294640 at the concentration up to 100μM. In MDA-MB-231 cells, ABC294640 decreased [3H]S1P formation in a dose-dependent manner with an IC50 value of 26μM. ABC294640 also inhibited the proliferation of human tumor cell lines (1025LU, A-498, Caco-2, HT-29, DU145, SK-OV-3) with IC50 values ranging from 10.5-48.1μM[2]. In a mouse model of tri-nitrobenzene sulfonic acid (TNBS)-induced colitis, oral administration of ABC294640 (50mg/kg, twice daily) decreased TNBS-induced increase in mucosal myeloperoxidase activity by 60%. The histological analysis on colon sections revealed that the inflammation and damage caused by TNBS was reduced or negated by ABC294640 treatment[3].
ABC294640/奥帕尼布 细胞实验
Cell Line
Concentration
Treated Time
Description
References
RAW264.7 cells
50 µM
24 hours
To test the effect of SPHK2 inhibitor on human monocytes and to evaluate inflammatory cytokine levels.
Cell Death Discov. 2023 Jan 18;9(1):12.
NSCLC cell-lines (A549, H460, H1299)
20 µM
48 hours
ABC294640 treatment caused significant G2 phase arrest and induced apoptosis in NSCLC cells.
Int J Cancer. 2018 May 15;142(10):2153-2162.
PC cell lines
15 mM
6 hours
To investigate the effect of SPHK inhibitors on ENZ resistance in cell line models.
EBioMedicine. 2021 Oct;72:103625.
ABC294640/奥帕尼布 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6J mice
ALI model induced by LPS
Intraperitoneal injection
20 mg/kg
Once after LPS administration
To alleviate macrophage-evoked oxidative injury and inflammatory reaction in lung tissues.
Cell Death Discov. 2023 Jan 18;9(1):12.
Mice
H460 xenograft model
Intraperitoneal injection
75 mg/kg
3 days/week for 3 weeks
ABC294640 treatment represses tumor growth in vivo.
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