Description
SKF-96365 (130495-35-1) is an inhibitor of receptor-mediated calcium entry (RMCE) with IC50‘s of 8.5 μM for ADP stimulated platelets and 11.7 μM for thrombin stimulated platelets. Also inhibits Voltage-gated Ca2+ but not ATP-gated Ca2+ entry.1 It has also been shown to block transient receptor potential canonical type (TRPC) channels2, high-voltage-activated (HVA) L-type channels1, K channels3, sarcoplasmic reticulum Ca-ATPase4 and voltage-gated sodium channels5. SKF-96365 is a potent blocker of LVA T-type Ca channels, in particular Ca(V)3.1 (IC50 = 0.56 μM).6
Uses
SKF 96365 Hydrochloride is a novel inhibitor of receptor-mediated calcium entry.
Definition
ChEBI: SKF-96365 hydrochloride is the hydrochloride salt of SKF-96365. It is a TRP channel blocker. It has a role as a TRP channel blocker, an apoptosis inducer, an autophagy inducer, a GABA antagonist, an antineoplastic agent, a calcium channel blocker and a platelet aggregation inhibitor. It contains a SKF-96365 free base(1+).
General Description
Inhibits receptor-mediated Ca2+ entry in stimulated platelets (IC50 = 8-12 μM in intact platelets), neutrophils, and endothelial cells (IC50 = 30 μM for human endothelial cells) at concentrations that do not affect internal Ca2+ release. Also inhibits voltage-gated Ca2+ entry in excitable cells. Inhibits the histamine-induced formation of nitric oxide in human endothelial cells.
Biological Activity
Store-operated Ca 2+ entry (SOCE) inhibitor that inhibits STIM1. Also inhibits TRP channels, voltage-gated Ca 2+ channels and potassium channels.
Biochem/physiol Actions
SKF-96365 with an alkylated imidazole ring is a selective inhibitor of receptor-mediated Ca2+?entry and voltage-gated Ca2+?entry . SKF-96365 mediated depolarization of smooth cardiac muscle membrane and had no impact on the acetylcholine (ACh)-induced depolarization. It is an inhibitor for SOCE (store-operated calcium entry). It also inhibits Homer1 protein expression. SKF-96365 elicits protective functionality in 1-methyl-4-phenylpyridinium(MPP) mediated cytotoxicity.
References
1) Merritt et al.,(1990) SKF96365, a novel inhibitor of receptor-mediated calcium entry; Biochem. J. 271 515
2) Kiselyov et al., (1998) Functional interaction between InsP3 receptors and store-operated Htrp3 channels; Nature, 396 478
3) Schwarz et al., (1994) Multiple effects of SKF96365 on ionic currents and intracellular calcium in human endothelial cells; Cell Calcium, 15 45
4) Mason et al., (1993) Inhibition of Ca2+ transport pathways in thymic lymphocytes by econazole, miconazole and SKF96365; Am. J. Physiol., 264 C654
5) Hong et al. (1994) Inhibition of the sodium channel by SKF96365, an inhibitor of the receptor-operated calcium channel, in mouse diaphragm; J. Biomed. Sci., 1 172
6) Singh et al.,(2010) The transient receptor potential channel antagonist SKF96365 is a potent blocker of low-voltage-activated T-type calcium channels; Br. J. Pharmacol., 160 1464
