A-803467

製品コードS2785 バッチS278501

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C19H16ClNO4
分子量 357.79 CAS No. 944261-79-4
Solubility (25°C)* 体外 DMSO 72 mg/mL (201.23 mM)
Ethanol 11 mg/mL (30.74 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
5%DMSO Corn oil
5.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 A-803467 is a selective NaV1.8 channel blocker with IC50 of 8 nM, blocks tetrodotoxin-resistant currents, exhibits >100-fold selectivity against human NaV1.2, NaV1.3, NaV1.5, and NaV1.7.
in vitro A-803467 potently blocks recombinant human or rat NaV1.8 channels with IC50 of 8 nM and 45 nM, respectively, at a holding potential of -40 mV. At a resting state, A-803467 also potently blocks human NaV1.8 channels with IC50 of 79 nM. A-803467 blocks tetrodotoxin-resistant (TTX-R) currents in rat dorsal root ganglion neurons in a concentration-dependent manner with IC50 of 140 nM, more potently compared with both mexiletine and lamotrigine with IC50 of >30 μM. A-803467 displays 300- to 1,000-fold higher selectivity for hNaV1.8 over hNaV1.2, hNaV1.3, hNaV1.5, and hNaV1.7 channels with IC50 of 7.38 μM, 2.45 μM, 7.34 μM, and 6.74 μM, respectively. A-803467 shows no significant activity against other channels and receptors expressed in peripheral sensory neurons including TRPV1, P2X2/3, CaV2.2 and KCNQ2/3 channels with IC50 >10 μM. A-803467 also shows no or weak activity against a broad screening panel of cell-surface receptors, ion channels, and enzymes with IC50 of >2 μM. A-803467 at 0.3 μM but not 0.1 μM significantly inhibits the generation of spontaneous and electrically evoked action potentials. [1]
in vivo Consistent with its effects on neuronal action potential electrogenesis in vitro, systemic administration of A-803467 (20 mg/kg, i.v.) to spinal nerve ligated rats, significantly reduces both spontaneous and von Frey hairevoked firing of spinal dorsal horn wide dynamic range neurons by 66% and 53%, respectively, compared with baseline levels. Administration of A-803467 also dose-dependently reduces mechanical allodynia in a variety of rat pain models including spinal nerve ligation (ED50 = 47 mg/kg, i.p.), sciatic nerve injury (ED50 = 85 mg/kg, i.p.), capsaicin-induced secondary mechanical allodynia (ED50 ≈ 100 mg/kg, i.p.), and thermal hyperalgesia after intraplantar complete Freund's adjuvant injection (ED50 = 41 mg/kg, i.p.). A-803467 is inactive against formalin-induced nociception and acute thermal and postoperative pain, as well as in a chemotherapy-induced pain model (vincristine). [1]
特徴 The 1st small-molecule blocker of sodium channels showing both high potency and significant subtype-selectivity among the sodium channel family.

プロトコル(参考用のみ)

キナーゼアッセイ Recombinant human sodium channels
HEK-293 cells expressing recombinant human NaV1.8 channels are grown in DMEM/high-glucose Dulbecco's modified, 10% FBS, 2 mM sodium pyruvate, and G418. For whole-cell voltage-clamp recordings, patch pipettes are pulled from borosilicate glass on a Flaming-Brown micropipette puller. Pipettes have a tip resistance of 0.8-2.5MΩ with the internal solutions 135 mM CsF, 10 mM CsCl, 5 mM EGTA, 5 mM NaCl, 10 mM Hepes, pH to 7.3, with 5 M CsOH, and voltage offset is zeroed before seal formation. The external buffer consists of 132 mM NaCl, 5.4 mM KCl, 0.8 mM MgCl2, 1.8 mM CaCl2, 5 mM Glucose, and 10 mM Hepes-free acid, pH to 7.3, with 6 M NaOH. After establishment of a whole-cell recording, cellular capacitance is minimized by using the analog compensation available on the recording amplifier. Series resistance is <5 MΩ and is compensated >85% in all experiments, resulting in a final series resistance no greater than 0.75 MΩ. Signals are low-pass filtered at 5-10 kHz, digitized at 20-50 kHz, and stored on a computer for later analysis. Voltage protocols are generated, and data acquisition and analysis are performed by using pCLAMP software. All experiments are performed at room temperature. Liquid junction potentials are <10mV and are not corrected. The concentration-response curve is generated after application of different concentrations of A-803467 and IC50 value of A-803467 is assessed at a holding potential of -40 mV.
動物実験 動物モデル Male Sprague–Dawley rats subjected to spinal nerve ligation, sciatic nerve injury, capsaicin-induced secondary mechanical allodynia, or thermal hyperalgesia after intraplantar complete Freund's adjuvant injection, and male CD1 mice subjected to the abdomi
投薬量 ~100 mg/kg
投与方法 Injected i.p. 30 minutes before behavioral testing

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Ropivacaine promotes axon regeneration by regulating Nav1.8-mediated macrophage signaling after sciatic nerve injury in rats [ Anesthesiology, 2023, 139(6):782-800.] PubMed: 37669448
Nav1.8 in keratinocytes contributes to ROS-mediated inflammation in inflammatory skin diseases [ Redox Biol, 2022, 55:102427] PubMed: 35952475

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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