吉西他濱作用機(jī)制 - Medchemexpress - MCE中國(guó)

1、Product Data SheetGemcitabineCat. No.: HY-17026CAS No.: 95058-81-4分式: CHFNO分量: 263.2作靶點(diǎn): Nucleoside Antimetabolite/Analog; DNA/RNA Synthesis; Autophagy; Apoptosis作通路: Cell Cycle/DNA Damage; Autophagy; Apoptosis儲(chǔ)存式: 4C, protect from light* In solvent : -80C, 6 months; -20C, 1 month (protect from ligh

2、t)溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 103.3 mg/mL (392.48 mM)Ethanol : 3.33 mg/mL (12.65 mM; Need ultrasonic)* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲(chǔ)備液1 mM 3.7994 mL 18.9970 mL 37.9939 mL5 mM 0.7599 mL 3.7994 mL 7.5988 mL10 mM 0.3799 mL 1.8997 mL 3.7994 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

3、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 (protect from light)。-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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/

4、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% salineSolubility: 2.58 mg/mL (9.80 mM); Clear solution此案可獲得 2.58 mg/mL (9.80 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.8 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-C

5、D in saline)Solubility: 2.58 mg/mL (9.80 mM); Clear solution此案可獲得 2.58 mg/mL (9.80 mM，飽和度未知) 的澄清溶液。Page 1 of 2 www.MedChemE以 1 mL 作液為例，取 100 L 25.8 mg/mL 的澄均勻。DMSO 儲(chǔ)備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.58 mg/mL (9.80 mM); Clear solution此案可獲得 2.58 mg/mL (9.

6、80 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 25.8 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Gemcitabine (LY 188011) 種嘧啶核苷類似物抗代謝藥 (nucleoside antimetabolite/analog) 和抗腫瘤劑。 Gemcitabine 抑制 DNA 合成 (DNA synthesis) 和修復(fù)，導(dǎo)致細(xì)胞噬 (autophagy) 和凋亡 (apoptosis)。Gemcitabine 抑制 BxPC-3，Mia

7、 Paca-2，PANC-1，PL-45 和 AsPC-1 細(xì)胞的長(zhǎng)，IC50 分別為 37.6 nM，42.9 nM，92.7 nM，89.3nM 和 131.4 nM。IC & Target DNA synthesis1體外研究 MTS assay demonstrates that Gemcitabine at 15 nM, indole-3-carbinol (I3C) at 50 M and the combination does notaffect hTERT-HPNE cell viability. However, treatment with Gemcitabine at

8、15 nM, I3C at 50 M and the combinationresults in 31%, 19% and 72% cell death of BxPC-3 cells, respectively1.體內(nèi)研究 Treatment of the LSL-KrasG12D/+; LSL-Trp53R172H; Pdx-1-Cre mice with either Gemcitabine (50 mg/kg, i.p.) or thecombination DMAPT/Gemcitabine significantly increased the median survival ti

9、me by more than 30 days compared tothe placebo group (254.5 P=0.015 or 255 days P=0.018 vs. 217.5 days, respectively)3. Gemcitabine can beadministered via endotracheal spray in rats without marked toxicity with a maximum tolerated dose of 4 mg/kg oncea week for 9 weeks. The toxicity of Gemcitabine i

10、s lower via lung than oral administration at dosages of 2, 4, and 6mg/kg2.PROTOCOLCell Assay 1 Cells (the human pancreatic cell lines, Mia PaCa-2, BxPC-3, AsPC-1, PANC-1, PL-45, and normal pancreatic ductalepithelial cells, hTERT-HPNE cells) are seeded into 96-well plates (3000 cells/well) in tripli

11、cate. After overnightincubation, the medium is changed and cells are treated with I3C and/or NBMPR for 24 h. The medium is changedagain and cells are cultured in medium containing different concentrations of Gemcitabine in the presence orabsence of the same concentrations of I3C and/or NBMPR for 48

12、h. The cells are then subjected to CellTiter 96AQueous One Solution Cell Proliferation Assay (MTS) as per the manufacturers instructions. Absorbance at 490 nm ismeasured 2 h after the addition of 20 L of MTS reagent/well1.MCE has not independently confirmed the accuracy of these methods. They are fo

13、r reference only.Animal Mice2Administration 23 At 1 month of age, LSL-KrasG12D/+; LSL-Trp53R172H; Pdx-1-Cre mice are randomized into treatment groups (placebo,DMAPT, Gemcitabine, DMAPT/Gemcitabine). Placebo (vehicle=hydroxylpropyl methylcellulose, 0.2% Tween 80HPMT) and DMAPT (40 mg/kg body weight i

14、n HPMT) are administered by oral gastric lavage once daily.Gemcitabine (50 mg/kg body weight in PBS) is administered by intraperitoneal injection twice weekly. Mouse weightis monitored weekly. Treatment is continued until mice show signs of lethargy, abdominal distension or weight lossat which time

15、they are sacrificed. Successful excision-recombination events are confirmed in the pancreata of mice bydetecting the presence of a single LoxP site.Rats3Page 2 of 3 www.MedChemEThe study is conducted in 80 female Wistar rats, with an initial weight of approximately 250 g. Animals are identifiedby ea

16、r mark and divided into groups as follows. Forty rats are divided into five groups of eight: four groups had lungdelivery of Gemcitabine via endotracheal spray at doses of 2, 4, 6, and 8 mg/kg, respectively (groups LD2, LD4, LD6,LD8), and one group receive a spray administration of the 0.9% saline v

17、ehicle solution (group LDv). The remaining 40rats are divided into five groups of eight: four groups have oral delivery of Gemcitabine via gavage at doses of 2, 4, 6,and 8 mg/kg, respectively (groups OD2, OD4, OD6, OD8), and one group receive an identical volume of 0.9% salinevia gavage (group ODv).

18、 The protocol includes nine sessions separated by 1-week intervals. Between sessions, theanimals are kept under standard laboratory conditions and housed by groups of four animals in each cage with litterand free access to pellet food and tap water. Cages are placed in a closed chamber connected to

19、an aspirationsystem.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) Nature. 2019 Oct;574(7777):264-267. Cell Res. 2020 Apr 27. Hepatology. 2019 May;69(5):1995-2012. J Mol Med (Berl). 2019 Aug;97(8):1183-1193. Am J Cancer Res. 2020 Apr 1;10(4

20、):1182-1193.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Wang H, et al. Enhanced efficacy of Gemcitabine by indole-3-carbinol in pancreatic cell lines: the role of human equilibrativenucleoside transporter 1.Anticancer Res. 2011 Oct;31(10):3171-80.2. Yip-Schneider MT, et al. Dimethylaminoparthenolide and Gemcitabine: a survival study using a genetically engineered mouse model of pancreaticcancer. BMC Cancer. 2013 Apr 17;13:194.3. Gagnadoux F, et al. Safety of pulmo