2-APB (Synonyms: 2-Aminoethoxydiphenyl borate, 2-APB, NSC 17107)

2-APB is a nonspecific antagonist of calcium channels, commonly used in studies of calcium signaling, such as in apoptosis, muscle contraction, and neural transmission. It is a membrane-permeable inhibitor of the inositol-1,4,5-trisphosphate (InsP3) sensitive Ca²⁺ channels, with an IC₅₀ value of 42μM when the concentration of InsP3 is 100nm^[1]. Additionally, 2-APB has been found to affect the activity of TRP channels at certain concentrations ^[2].

In vitro, 2-APB can inhibit the increase in intracellular Ca²⁺ induced by thrombin in human platelets and neutrophils, as well as angiotensin II (AII)-induced contraction of the thoracic aorta ^[1]. In HEK-293 cells, 2-APB blocks the TRPC5 channel with an IC₅₀ value of 20 μM ^[3]. In mouse pancreatic acinar cells, low concentrations of 2-APB significantly inhibit calcium store-operated calcium influx, while high concentrations inhibit direct stimulation-induced Ca²⁺ release and InsP3-induced Ca²⁺ release ^[4].

In vivo, when 2-APB is administered intravenously at 10 mg/kg to mice in an I/R model, it significantly reduces the infarct size, accompanied by a reduction in ROS levels and neutrophil infiltration, demonstrating potential cardioprotective effects ^[5]. Additionally, in I/R rats, 2-APB significantly increases superoxide dismutase (SOD), total antioxidant capacity (TAC), and glutathione (GSH), while reducing malondialdehyde (MDA) and DNA fragmentation, indicating that 2-APB has anti-apoptotic and antioxidative effects ^[6].

References:

[1]. Maruyama T, Kanaji T, Nakade S, et al. 2APB, 2-aminoethoxydiphenyl borate, a membrane-penetrable modulator of Ins(1,4,5)P3-induced Ca2+ release. J Biochem, 1997, 122(3): 498-505..

[2]. Togashi K , Inada H , Tominaga M .Inhibition of the transient receptor potential cation channel TRPM2 by 2-aminoethoxydiphenyl borate (2-APB)[J].British Journal of Pharmacology, 2008.

[3].Xu SZ, Zeng F, Boulay G, et al. Block of TRPC5 channels by 2-aminoethoxydiphenyl borate: a differential, extracellular and voltage-dependent effect. Br J Pharmacol, 2005, 145(4): 405-414.

[4]. Choi KJ, Kim KS, Kim SH, et al. Caffeine and 2-Aminoethoxydiphenyl Borate (2-APB) Have Different Ability to Inhibit Intracellular Calcium Mobilization in Pancreatic Acinar Cell. Korean J Physiol Pharmacol, 2010, 14(2): 105-111.

[5]. Hirofumi M , Masanori O , Shota T ,et al.2-aminoethoxydiphenyl borate provides an anti-oxidative effect and mediates cardioprotection during ischemia reperfusion in mice[J].Plos One, 2017, 12(12).

[6]. Sari E, Aksit H, Erken HA, et al. Protective effect of 2-APB on testicular ischemia-reperfusion injury in rats. J Urol, 2015, 193(3): 1036-1041.