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A-803467

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Chemical Structure| 944261-79-4 同义名 : -
CAS号 : 944261-79-4
货号 : A630517
分子式 : C19H16ClNO4
纯度 : 99%+
分子量 : 357.788
MDL号 : MFCD10574689
存储条件：

粉末 Sealed in dry,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(139.75 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

2% DMSO+corn oil 5 mg/mL

生物活性
靶点

  • Sodium Channel

    Na(V1.8) channel, IC50:8 nM
描述 A-803467 is a potent and selective tetrodotoxin-resistant Nav1.8 sodium channel blocker (IC50=8 nM). A-803467 (20 mg/kg, i.v.) blocked mechanically evoked firing of wide dynamic range neurons in the rat spinal dorsal horn. A-803467 also dose-dependently reduced mechanical allodynia in a variety of rat pain models including: spinal nerve ligation (ED(50) = 47 mg/kg, i.p.), sciatic nerve injury (ED(50) = 85 mg/kg, i.p.), capsaicin-induced secondary mechanical allodynia (ED(50) approximately 100 mg/kg, i.p.), and thermal hyperalgesia after intraplantar complete Freund's adjuvant injection (ED(50) = 41 mg/kg, i.p.)[3]. A-803467 selectively and significantly reverses the ABCG2-mediated multidrug resistance. A-803467 (7.5 μM) significantly increased the intracellular accumulation of [(3)H]-mitoxantrone by inhibiting the transport activity of ABCG2, without altering its expression levels. In addition, A-803467 stimulated the ATPase activity in membranes overexpressed with ABCG2. In a murine model system, combination treatment of A-803467 (35 mg/kg) and topotecan (3 mg/kg) significantly inhibited the tumor growth in mice xenografted with ABCG2-overexpressing cancer cells[4]. A-803467 significantly shortened ventricular effective refractory period, APD90, and ventricular fibrillation threshold compared to control. In the A-803467 group, the incidence of ventricular arrhythmias was significantly higher compared to control. A-803467 suppressed the slowing of heart rate response to high-frequency electrical stimulation of the anterior right GP(ganglionated plexi), suggesting that A-803467 could inhibit GP activity[5].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.79mL

0.56mL

0.28mL

13.97mL

2.79mL

1.40mL

27.95mL

5.59mL

2.79mL
参考文献

[1]Joshi SK, Honore P, et al. Additive antinociceptive effects of the selective Nav1.8 blocker A-803467 and selective TRPV1 antagonists in rat inflammatory and neuropathic pain models. J Pain. 2009 Mar;10(3):306-15.

[2]Jarvis MF, Honore P, et al. A-803467, a potent and selective Nav1.8 sodium channel blocker, attenuates neuropathic and inflammatory pain in the rat. Proc Natl Acad Sci U S A. 2007 May 15;104(20):8520-5. Epub 2007 May 2.

[3]Jarvis MF, Honore P, Shieh CC, Chapman M, Joshi S, Zhang XF, Kort M, Carroll W, Marron B, Atkinson R, Thomas J, Liu D, Krambis M, Liu Y, McGaraughty S, Chu K, Roeloffs R, Zhong C, Mikusa JP, Hernandez G, Gauvin D, Wade C, Zhu C, Pai M, Scanio M, Shi L, Drizin I, Gregg R, Matulenko M, Hakeem A, Gross M, Johnson M, Marsh K, Wagoner PK, Sullivan JP, Faltynek CR, Krafte DS. A-803467, a potent and selective Nav1.8 sodium channel blocker, attenuates neuropathic and inflammatory pain in the rat. Proc Natl Acad Sci U S A. 2007 May 15;104(20):8520-5

[4]Anreddy N, Patel A, Zhang YK, Wang YJ, Shukla S, Kathawala RJ, Kumar P, Gupta P, Ambudkar SV, Wurpel JN, Chen ZS, Guo H. A-803467, a tetrodotoxin-resistant sodium channel blocker, modulates ABCG2-mediated MDR in vitro and in vivo. Oncotarget. 2015 Nov 17;6(36):39276-91

[5]Qi B, Dai S, Song Y, Shen D, Li F, Wei L, Zhang C, Nie Z, Lin J, Cai L, Ge J. Blockade of NaV1.8 Increases the Susceptibility to Ventricular Arrhythmias During Acute Myocardial Infarction. Front Cardiovasc Med. 2021 Aug 2;8:708279