卡培他濱作用機(jī)制 - Medchemexpress - MCE中國

1、Product Data SheetCapecitabineCat. No.: HY-B0016CAS No.: 154361-50-9分式: CHFNO分量: 359.35作靶點(diǎn): DNA/RNA Synthesis; Nucleoside Antimetabolite/Analog; Apoptosis作通路: Cell Cycle/DNA Damage; Apoptosis儲(chǔ)存式: Powder -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 (278.28 mM;

2、Need ultrasonic)H2O : 33.33 mg/mL (92.75 mM)* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲(chǔ)備液1 mM 2.7828 mL 13.9140 mL 27.8280 mL5 mM 0.5566 mL 2.7828 mL 5.5656 mL10 mM 0.2783 mL 1.3914 mL 2.7828 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：-8

3、0C, 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?。以下溶解案都?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% PEG300 5% Tween-80 45% salineSolu

4、bility: 10 mg/mL (27.83 mM); Clear solution此案可獲得 10 mg/mL (27.83 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 100.0 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% (20% SBE-CD in saline)Solubility: 10 mg/mL (27.83 mM); Clear solutionPage 1 of

5、 2 www.MedChemE此案可獲得 10 mg/mL (27.83 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 100.0 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: 10 mg/mL (27.83 mM); Clear solution此案可獲得 10 mg/mL (27.83 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 100.0 mg/mL

6、的澄 DMSO 儲(chǔ)備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Capecitabine種可于服的前藥，可由胸苷磷酸化酶催化轉(zhuǎn)變?yōu)槠浠钚源x物 Fluorouracil (FU)。IC & Target DNA/RNA Synthesis1體外研究 Capecitabine is an anti-cancer chemotherapy drug. It is classified as an antimetabolite. Capecitabine is converted into5-deoxy-5-fluorocytidine (5DFCR), 5-d

7、eoxy-5-fluorouridine (5DFUR) and 5-FU by carboxylesterases (CES1 and 2),cytidine deaminase (CDD), and thymidine phosphorylase (TP), in both liver and tumour. Capecitabine induces asignificant cytotoxic effect in vitro only at high concentrations. Mean IC50 values vary from 860 M in COLO205 cellsto 6

8、000 M in HCT8 cells2.體內(nèi)研究 A pharmacokinetic/pharmacodynamic study is carried out in mice bearing HCT 116 xenografts receiving 0.52 and 2.1 mmol/kg/d of Capecitabine by oral gavage. Capecitabine administered at 0.52 mmol/kg/day induces partial control of HCT 116 xenografts tumour growth: growth rate

9、=7.50.5 on day 21. Capecitabine 2.1 mmol/kg/day achievescomplete control of tumor growth during the treatment period: growth rate =10.2 on day 212.PROTOCOLCell Assay 2 HCT 116, HCT8, HCT15, HT29, SW620 and COLO205 human colon cancer cells are used. Cells are plated on day 1 in96-well plates at a den

10、sity of 2500 cells/well for HCT 116, 3500 cells/well for HCT8 and HT29, 5000 cells/well forHCT15, 6000 cells/well for SW620 and 7000 cells/wells for COLO205 in a volume of 150 L/well. All cell lines aretreated on day 2 with increasing concentrations of Capecitabine (0.1-10 mM), 5DFCR (10 nM-100 M),

11、5DFUR (2.5-500 M) or 5-FU (0.5-250 M) for 24 h. After drug exposure, cells are washed once with cold PBS and placed in 200 L of drug-free medium for 72 h after the end of drug exposure. The cells are then fixed with trichloroacetic acid andstained with sulforhodamine B. Optical densities are measure

12、d at 540 nm with a Biohit BP-800. The results are basedon three independent experiments performed in triplicate2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice2Administration 2 Six-week-old C57/Bl6 Nu/Nu mice are used. Bilateral HCT 116 xen

13、ografts are obtained by subcutaneous injection of107 cells/flank. Animals bearing HCT 116 xenografts are treated with vehicle or Capecitabine 0.52 or 2.1 mmol/kg(563 and 2250 mg/m2, respectively) given once daily for 5 consecutive days/week by oral gavage for 3 weeks (days 0-4, 7-11, 14-18). Animals

14、 are culled on day 0 at 15, 30 min, 1, 2, 4, 8 and 24 h, and prior to planned treatment on days7 and 14 after the start of treatment. Three animals per time-point are analysed. At the time of collection, blood iscollected in heparin, and plasma isolated and stored at 80C. The liver is removed immedi

15、ately and stored inRNAlater solution. Tumours are macro-dissected to remove fibrotic tissue and blood vessels and snap-frozen inliquid nitrogen.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Page 2 of 3 www.MedChemE戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Cancer Lett. 2020 Feb 12.

16、 pii: S0304-3835(20)30069-0. J Mol Med (Berl). 2019 Aug;97(8):1183-1193. Acta Pharmacol Sin. 2020 May 12.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. PharmD CM, et al. Capecitabine: A review. Clinical Therapeutics. 2005 Jan; 27(1): 23-44.2. Guichard SM, et al. Gene expression predicts differential capecitabine metabolism, impacting on both pharmacokinetics and antitumour activity. Eur JCan