氟芬那酸作用机制 - Medchemexpress - MCE中国

1、Product Data SheetFlufenamic acidCat. No.: HY-B1221CAS No.: 530-78-9分式: CHFNO分量: 281.23作靶点: 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储存式: Powde

2、r -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 100 mg/mL (355.58 mM; Need ultrasonic)SolventMass1 mg 5 mg 10 mgConcentration制备储备液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请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；旦配成溶液，请分

3、装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 储存时，请在 6 个内使，-20C 储存时，请在 1 个内使。体内实验请根据您的实验动物和给药式选择适当的溶解案。以下溶解案都请先按照 In Vitro 式配制澄清的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 40% PE

4、G300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (8.89 mM); Clear solution此案可获得 2.5 mg/mL (8.89 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 400 L PEG300 中，混合均匀；向上述体系中加50 L Tween-80，混合均匀；然后继续加 450 L 理盐定容 1 mL。2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (8.89 mM); Clear s

5、olutionPage 1 of 2 www.MedChemE此案可获得 2.5 mg/mL (8.89 mM，饱和度未知) 的澄 溶液，此案不适于实验周 期在半个以上的实验。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 900 L 油中，混合均匀。BIOLOGICAL ACTIVITY物活性 Flufenamic acid 种甾体类抗炎剂，能够抑制 COX 的活性，激活 AMPK 的活性，调节离通道，阻滞氯离通道 (chloride channel) 和 L-型钙离通道 (L-type Ca2+ channel)，调节选择性阳离通道，激活钾离通道

6、(K+ channel) 等。IC & Target COX, Chloride Channel, Calcium Channel, Potassium Channel1, AMPK2体外研究 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.体内研究 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.户使本产品发表的科研献 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