特非那定作用機(jī)制 - Medchemexpress - MCE中國(guó)

1、Product Data SheetTerfenadineCat. No.: HY-B1193CAS No.: 50679-08-8分式: CHNO分量: 471.67作靶點(diǎn): Potassium Channel; Histamine Receptor; Na+/Ca2+ Exchanger; Caspase;Apoptosis作通路: Membrane Transporter/Ion Channel; GPCR/G Protein;Immunology/Inflammation; Neuronal Signaling; Apoptosis儲(chǔ)存式: Powder -20C 3 years4C

2、2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 50 mg/mL (106.01 mM)H2O : 0.1 mg/mL (insoluble)* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲(chǔ)備液1 mM 2.1201 mL 10.6006 mL 21.2013 mL5 mM 0.4240 mL 2.1201 mL 4.2403 mL10 mM 0.2120 mL 1.0601 mL 2.1201 mL請(qǐng)根據(jù)產(chǎn)

3、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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的

4、式助溶1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.30 mM); Clear solution此案可獲得 2.5 mg/mL (5.30 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。Page 1 of 2 www.MedChemE2. 請(qǐng)依序添加每種溶劑： 10% D

5、MSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.30 mM); Clear solution此案可獲得 2.5 mg/mL (5.30 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 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.30 mM); Clear solution此案可獲得 2.5 mg/mL (5.30 mM，飽和度

6、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 Terfenadine ()-Terfenadine)種有效的 hERG 開(kāi)放通道抑制劑, IC50為 204 nM。Terfenadine 也 種 H1 組胺受體 (histamine receptor) 拮抗劑，通過(guò)調(diào)節(jié) Ca2+ 穩(wěn)態(tài)在素瘤細(xì)胞中起到有效的細(xì)胞凋亡誘導(dǎo)作。 Terfenadine 誘導(dǎo) ROS 依賴(lài)性細(xì)胞凋亡，同時(shí)激活 Caspase-4，-2，-9。I

7、C & Target Caspase-4 Caspase-2 Caspase-9體外研究Terfenadine ()-Terfenadine) (4-20 M; 24 hours) induces dose and time-dependent apoptosis on A375 melanomacells. The IC50 after 24 h of TEF treatment in complete medium was 10.4 M for A375 cells, 9.9 M for Hs294T cellsand 9.6 for HT144 cells2.Terfenadine (2

8、-10 M; 8 hours) induces dose-dependent cytotoxicity2.Terfenadine (10 M; 8 hours) causes a massive vacuolization of the cytoplasm and autophagic vacuoles of bothdouble and multiple membranes and at various stages. Terfenadine induces autophagy by ROS-dependent and -independent mechanisms2.Apoptosis A

9、nalysis2Cell Line: A375, HT144 and Hs294T cellsConcentration: 4, 8, 12, 16, 20 MIncubation Time: 24 hoursResult: Induced dose and time-dependent apoptosis.Cell Cytotoxicity Assay2Cell Line: A375 melanoma cellsConcentration: 2, 4, 6, 8, 10 MIncubation Time: 8 hoursResult: Induces dose-dependent cytot

10、oxicity.Cell Autophagy Assay2Cell Line: A375 cellsConcentration: 10 MPage 2 of 3 www.MedChemEIncubation Time: 8 hoursResult: Caused a massive vacuolization of the cytoplasm and autophagic vacuoles of bothdouble and multiple membranes and at various stages.體內(nèi)研究 Terfenadine (p.o.; 40 mg/kg; for 16 day

11、s) produces a significant inhibition of tumour growth rate and enhances theanti-cancer effect of EPI in chemo-resistant NSCLC xenograft models3.Animal Model: 6-week-old male BALB/cA-nu mice3Dosage: 40 mg/kgAdministration: P.o.; for 16 daysResult: Produced a significant inhibition of tumour growth ra

12、te.REFERENCES1. Kamiya K, et al. Molecular determinants of hERG channel block by terfenadine and cisapride. J Pharmacol Sci. 2008 Nov;108(3):301-307.2. Nicolau-Galms F, et al. Terfenadine induces apoptosis and autophagy in melanoma cells through ROS-dependent and -independent mechanisms.Apoptosis. 2011 Dec;16(12):1253-67.3. An L, et al. Terfenadine combined with epirubicin impedes the chemo-resistant human non-small cell lung cancer both in vitro and in vivo through EMTand Notch reversal. Pharmacol Res. 2017 Oct;124:105-115.McePdfHeightCaution: Product h