A-803467

A-803467 is a potent and selective tetrodotoxin-resistant Na_v1.8 sodium channel blocker (IC₅₀=8 nM). A-803467 has shown significant anti-nociception in neuropathic and inflammatory pain models. A-803467 enhances the chemosensitivity of conventional anticancer agents through interaction with the ATP-binding cassette subfamily G member 2 (ABCG2) transporter^[1][2]. IC50 & Target: IC50：8 nM (Na_v1.8 sodium channel)^[2] In Vitro: A-803467 selectively and significantly reverses the ABCG2-mediated multidrug resistance. A-803467 (7.5 μM) significantly increases the cytotoxicity of mitoxantrone and topotecan in ABCG2-transfected cell lines. A-803467 (7.5 μM) significantly enhanced theintracellular [³H]-MX accumulation in ABCG2-transfected cells. A-803467 (7.5 μM; 0~120 minutes) significantly blocks the intracellular [³H]-MX efflux at different time periods from ABCG2-transfected cells. A-803467 stimulates the ATPase activity of ABCG2^[1]. In Vivo: A-803467 (35 mg/kg; p.o.) shows no noticeable toxicity in the male NCR nude mice^[1].
A-803467 in combination with topotecan, significantly decreases the tumor growth in mice implanted with ABCG2 overexpressing H460/MX20 cells. A-803467 effectively restores the sensitivity of tumors overexpressing ABCG2 transporter to topotecan without having any significant effect on tumors lacking ABCG2 expression^[1].