氟芬那酸作用機(jī)制 - Medchemexpress - MCE中國(guó)

1、Product Data SheetFlufenamic acidCat. No.: HY-B1221CAS No.: 530-78-9分式: CHFNO分量: 281.23作靶點(diǎn): COX; AMPK; Potassium Channel; Chloride Channel; Calcium Channel; Parasite作通路: Immunology/Inflammation; Epigenetics; PI3K/Akt/mTOR; MembraneTransporter/Ion Channel; Neuronal Signaling; Anti-infection儲(chǔ)存式: Powde

2、r -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 100 mg/mL (355.58 mM; Need ultrasonic)SolventMass1 mg 5 mg 10 mgConcentration制備儲(chǔ)備液1 mM 3.5558 mL 17.7790 mL 35.5581 mL5 mM 0.7112 mL 3.5558 mL 7.1116 mL10 mM 0.3556 mL 1.7779 mL 3.5558 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；旦配成溶液，請(qǐng)分

3、裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)內(nèi)使，-20C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍浮Ｒ韵氯芙獍付颊?qǐng)先按照 In Vitro 式配制澄清的儲(chǔ)備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PE

4、G300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (8.89 mM); Clear solution此案可獲得 2.5 mg/mL (8.89 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (8.89 mM); Clear s

5、olutionPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (8.89 mM，飽和度未知) 的澄 溶液，此案不適于實(shí)驗(yàn)周 期在半個(gè)以上的實(shí)驗(yàn)。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Flufenamic acid 種甾體類抗炎劑，能夠抑制 COX 的活性，激活 AMPK 的活性，調(diào)節(jié)離通道，阻滯氯離通道 (chloride channel) 和 L-型鈣離通道 (L-type Ca2+ channel)，調(diào)節(jié)選擇性陽(yáng)離通道，激活鉀離通道

6、(K+ channel) 等。IC & Target COX, Chloride Channel, Calcium Channel, Potassium Channel1, AMPK2體外研究 Flufenamic acid is a non-steroidal anti-inflammatory agent, inhibits cyclooxygenase (COX), and also modulates ionchannels, blocking chloride channels and L-type Ca2+ channels, modulating non-selective ca

7、tion channels (NSC),activating K+ channels. Flufenamic acid inhibits a wide spectrum of TRP channels, including: C3, C7, M2, M3, M4, M5,M7, M8, V1, V3, and V4 but activates at least two TRP channels (C6 and A1)1. Flufenamic acid induces AMPKactivation in T84 cells, and such an effect is via a direct

8、 stimulation of calcium/calmodulin-dependent protein kinasekinase beta (CaMKK) activity2. Moreover, Flufenamic acid (FFA; 5-50 M) dose-dependently inhibits cAMP-dependent Cl- secretion in intact T84 cells, suppresses CFTR-mediated apical ICl-, and blocks the Ca2+-dependent Cl-secretion in a dose-dep

9、endent manner with IC50 of appr 10 M and near complete inhibition at 100 M in T84 cellmonolayers, but shows no effect on Na+-K+ ATPase or NKCC in T84 cells3.體內(nèi)研究 Flufenamic acid (50 mg/kg, i.p.) has anti-inflammatory effect in a mouse model of Vibrio cholerae El Tor variant (EL)-induced diarrhea and

10、 significantly abrogates EL-induced intestinal fluid secretion and barrier disruption at 20 mg/kg.Furthermore, Flufenamic acid suppresses NF-B nuclear translocation and expression of proinflammatory mediatorsand promotes AMPK phosphorylation in the EL-infected mouse intestine2.PROTOCOLCell Assay 3 I

11、n brief, apical and basolateral chambers are filled symmetrically with Krebs solutions. Thereafter, DMSO orFlufenamic acid is added into the basolateral chamber followed by apical membrane permealization by amphotericinB. After the amphotericin B-elicited Isc is stabilized, ouabain is added into the

12、 basolateral chamber. The ouabainsensitive Isc is used as an indicator of Na+-K+ ATPase activity3.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Rats2Administration 2 Six-week-old male ICR outbred mice (weight 30-35 g) are fasted for 24 h before

13、 anesthesia using an intraperitonealinjection of nembutal (60 mg/kg). Following abdominal incision, the ileum is ligated (appr 3-4 cm long) andinoculated with 100 L of PBS or PBS containing V. cholerae (105 CFU/loop) with or without a concomitantintraperitoneal injection of Flufenamic acid or metfor

14、min. Twelve hours post-inoculation, ileal loops are removed forweight/length ratio measurement, biochemical analysis and ultrastructural evaluation2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Neurosci Lett. 2020 May 25;135088.Page 2 of

15、3 www.MedChemE Neurosci Lett. 2019 Mar 23;696:67-73.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Guinamard R, et al. Flufenamic acid as an ion channel modulator. Pharmacol Ther. 2013 May;138(2):272-84.2. Pongkorpsakol P, et al. Flufenamic acid protects against int

16、estinal fluid secretion and barrier leakage in a mouse model of Vibrio cholerae infectionthrough NF-B inhibition and AMPK activation. Eur J Pharmacol. 2017 Mar 5;798:94-104.3. Pongkorpsakol P, et al. Cellular mechanisms underlying the inhibitory effect of flufenamic acid on chloride secretion in human intestinal epithelial cells. JPharmacol Sci. 2