ARC39

ARC39 (1 µM; 3-5 min) blocks platelet- and rhASM-promoted B16F10 melanoma cell adhesion to fibronectin^[2].

ARC39 (0.1 µM; 7 h) protects HepG2 cells from Dexamethasone (HY-14648)-induced apoptosis^[1].
ARC39 (5-160 µM; 24-48 h) has low acute in vitro toxicity at ASM-inhibitory concentrations, with reduced L929 and HepG2 viability at ≥40 µM after 48 h^[2].

ARC39 (1-3 μM) in wild-type mouse ventral hippocampal CA1 field recordings rapidly and reversibly enhances Schaffer-collateral fEPSPs and reduces paired-pulse ratio, with no effect in ASM-KO slices; ASM IC₅₀ 0.02 μM^[3].

ARC39 (compound 7c; 3 h at 37 °C) is a potent inhibitor of rat-brain aSMase with an IC₅₀ of 0.02 µM and retains activity in the presence of millimolar divalent metal ions^[1].
ARC39 (Up to 100 µM) does not substantially inhibit Mg²⁺-dependent nSMase in rat-brain preparations (IC₅₀ >100 µM)^[1].
ARC39 (0.3-0.5 µM) directly and selectively inhibits L-ASM and S-ASM in micellar assays, with a reported IC₅₀ of 20 nM and near-complete L-ASM inhibition at 0.3-0.5 µM^[2].
ARC39 (0.5-80 µM) does not directly inhibit SphK1 or SphK2 in cell-free assays up to 80 µM^[2].
ARC39 selectively inhibits ASM catalytic activity without inhibiting neutral sphingomyelinase, acid ceramidase, or neutral ceramidase in L929 cells^[2].
ARC39 (40 µM; 2-24 h) inhibits ASM catalytic activity without downregulating SMPD1/Smpd1 mRNA or ASM protein in L929 and HepG2 cells^[2].
ARC39 (20 µM; 2-24 h) inhibits L-ASM in intact L929 and HepG2 cells in a dose- and time-dependent manner, with 20 µM producing near-maximal inhibition by approximately 6 h^[2].
ARC39 (20 µM; 2-24 h) increases sphingomyelin and reduces ceramide/S1P in L929 and HepG2 cells, consistent with ASM inhibition^[2].
ARC39 (10-20 µM; 24 h) does not induce significant phospholipidosis in L929 cells^[2].
ARC39 (1 μM; 7-9 min) in wild-type mouse ventral CA1 pyramidal cells with intact synaptic input predominantly hyperpolarizes cells and suppresses ramp-evoked action potentials, while ASM-KO cells are unaffected^[3].
ARC39 (1 μM fluorescent substrate) inhibits recombinant ASM with an IC₅₀ of ∼50 nM in the presence of 1 μM fluorescent substrate^[5].
ARC39 (10 μM; 1-24 h) alters the sphingolipid profile in HuLEC cells over 1-24 h^[5].
ARC39 (10 μM; 18 h) inhibits secreted ASM in supernatants from Ionomycin (HY-13434)-treated HuLEC cells^[5].

ARC39 (10 µM; 24 h) causes lysosomal accumulation of exogenous sphingomyelin in L929 and HepG2 cells^[2].

ARC39 (2-24 h) minimally affects the lysosomal compartment at 2 h but increases LysoTracker signal after 24 h in L929 cells^[2].

ARC39 (1-4 μM; 21 h pretreatment; 3 h necroptosis induction) restores cell viability during necroptosis in HT-29 cells in a concentration-dependent manner^[4].
ARC39 (1-4 μM; 21 h pretreatment; 3 h necroptosis induction) decreases LDH release during necroptosis in HT-29 cells, supporting protection of plasma membrane integrity^[4].
ARC39 (4 μM; 3 h necroptosis induction) preserves MLKL phosphorylation and membrane association during necroptosis in HT-29 cells, indicating action downstream of MLKL activation^[4].

ARC39 (4 μM; 21 h pretreatment; 3 h necroptosis induction) suppresses necroptosis-associated ceramide accumulation, decreasing total ceramides two-fold in HT-29 cells^[4].