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）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
5%DMSO Corn oil

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 5.000mg/ml (13.97mM) 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, this compound also potently blocks human NaV1.8 channels with IC50 of 79 nM. It 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. This chemical 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. It 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. This compound also shows no or weak activity against a broad screening panel of cell-surface receptors, ion channels, and enzymes with IC50 of >2 μM. It 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 this compound 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.). This chemical 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 this compound and IC50 value of this chemical 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

参考

  • https://pubmed.ncbi.nlm.nih.gov/17483457/
  • https://pubmed.ncbi.nlm.nih.gov/19070548/

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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