特非那定作用机制 - Medchemexpress - MCE中国

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

2、2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 50 mg/mL (106.01 mM)H2O : 0.1 mg/mL (insoluble)* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制备储备液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请根据产

3、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

4、式助溶1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.30 mM); Clear solution此案可获得 2.5 mg/mL (5.30 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。Page 1 of 2 www.MedChemE2. 请依序添加每种溶剂： 10% D

5、MSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.30 mM); Clear solution此案可获得 2.5 mg/mL (5.30 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 900 L 20% 的 SBE-CD 理盐溶液中，混合均匀。3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.30 mM); Clear solution此案可获得 2.5 mg/mL (5.30 mM，饱和度

6、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 Terfenadine ()-Terfenadine)种有效的 hERG 开放通道抑制剂, IC50为 204 nM。Terfenadine 也 种 H1 组胺受体 (histamine receptor) 拮抗剂，通过调节 Ca2+ 稳态在素瘤细胞中起到有效的细胞凋亡诱导作。 Terfenadine 诱导 ROS 依赖性细胞凋亡，同时激活 Caspase-4，-2，-9。I

7、C & Target Caspase-4 Caspase-2 Caspase-9体外研究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.体内研究 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