1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEGemcitabine HydrochlorideCat. No.: HY-B0003CAS No.: 122111-03-9Synonyms: LY 188011 hydrochloride分式: CHClFNO分量: 299.66作靶點: DNA/RNA Synthesis; Nucleoside Antimetabolite/Analog;Autophagy作通路: Cell Cycle/DNA Damage; Autophagy儲存式: Pow

2、der -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數據體外實驗 H2O : 66.66 mg/mL (222.45 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 3.3371 mL 16.6856 mL 33.3712 mL5 mM 0.6674 mL 3.3371 mL 6.6742 mL10 mM 0.3337 mL 1.6686 mL 3.3371 mL請根據產品在不同

3、溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 Gemcitabine (Hydrochloride)種DNA合成抑制劑，在131.4 nM -2，PANC-1，PL-45和AsPC-1細胞中的IC50 分別為37.6，42.9，92.7，89.3 和 131.4 nM。IC50 & Target DNA synthesis 11/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE體外研究 MTS assay demonstrates that Gemcitabine (Hydro

4、chloride) at 15 nM, indole-3-carbinol (I3C) at 50 M andthe combination does not affect hTERT-HPNE cell viability. However, treatment with Gemcitabine(Hydrochloride) at 15 nM, I3C at 50 M and the combination results in 31%, 19% and 72% cell death ofBxPC-3 cells, respectively 1.體內研究 The aim of study i

5、s to formulate PLGA nanoparticles (NPs) of Gemcitabine (Hydrochloride, Gemcitabine HCl)for enhanced oral bioavailability via absorption through M cells of Peyers patches. Gemcitabine HCl isavailable as i.v. infusion due to its short half life (8-17 min), rapid metabolism and limited tumor uptake.Gem

6、citabine loaded PLGA NPs shows 21.47-fold increase in relative bioavailability in comparison to plaindrug solution after oral delivery 2. After i.v. injection of Gemcitabine at doses of 50, 100, and 120, and 300mg/kg, the highest dose caused considerable body weight loss (p10) and 100 mg/kg is consi

7、dered as themaximal tolerated dose, which does not cause any mortality and a minimal body weight loss 3.PROTOCOLCell Assay 12 Cells (the human pancreatic cell lines, Mia PaCa-2, BxPC-3, AsPC-1, PANC-1, PL-45, and normal pancreaticductal epithelial cells, hTERT-HPNE cells) are seeded into 96-well pla

8、tes (3000 cells/well) in triplicate. Afterovernight incubation, the medium is changed and cells are treated with I3C and/or NBMPR for 24 h. Themedium is changed again and cells are cultured in medium containing different concentrations ofGemcitabine in the presence or absence of the same concentrati

9、ons of I3C and/or NBMPR for 48 h. Thecells are then subjected to CellTiter 96 AQueous One Solution Cell Proliferation Assay (MTS). Absorbance at490 nm is measured 2 h after the addition of 20 L of MTS reagent/well 1.The in vitro cytotoxicity of Gemcitabine HCl loaded NPs on Caco-2 cells are performe

10、d for 6 h to check thetoxicity of NPs during the transport/permeability studies and antiproliferative effect on K562 cells is evaluatedfor 48 h using the MTT assay. The cells are cultured in 96-well plates at a seeding density of 1.0104cells/well for 48 h. Experiments are initiated by replacing the

11、culture medium in each well with 150 L ofsample solutions (0.1, 1, 10, 100 g/mL) at 37C in the CO2 incubator. After 4, 24 and 48 h of incubation, themedium is removed and 150 L of MTT reagent (1 mg/mL) in the serum-free medium is added to each well.The plates are then incubated at 37C for another 4

12、h. At the end of the incubation period, the medium isremoved and the intracellular formazan is solubilized with 150 L DMSO and quantified by reading theabsorbance at 590 nm on a micro-plate multi-detection instrument, SpectraMax M2 with Soft Max Pro. Themedium treated cells serve as controls. Percen

13、tage cell viability is calculated based on the absorbancemeasured relative to the absorbance of cells exposed to the negative control 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Rats 2Administration 23 Three groups of male Wistar rats (n=6)

14、 are subjected to single oral dose bioavailability study. Theformulations are administered orally with the aid of a syringe and infant feeding tube. The 1st group is givendistilled water, the 2nd group is given a solution of Gemcitabine HCl in distilled water, and the third groupreceived Gemcitabine

15、 HCl loaded NPs at a dose of 10 mg/kg. Blood samples (0.3 mL) are drawn by retro-orbital venous plexus puncture with the aid of capillary tubes at 0.5, 1, 2, 4, 24, 48, 72 h post oral dose. Thesamples are collected in heparinised Eppendorf tubes containing 10 M tetrahydrouridine, centrifuged at3400

16、rpm for 15 min and plasma is collected. To this, 200 L of Acetonitrile is added and vortexed for 5 min2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEfollowed by centrifugation at 5000 rpm for 15 min. The organic phase is separated and evaporated underreduced pressure in a vacuum oven. The residue

17、is dissolved in mobile phase (0.15 mL), vortexed for 1 minfollowed by centrifugation at 13,000 rpm for 5 min. Then 20 L of supernatant is injected into the HPLCcolumn and analyzed by HPLC.Mice 3DBA/2 mice (5-6 weeks old), weighing approximately 15 to 18 g, are used for the study. The mice areprovide

18、d with standard mouse food and water ad libitum. The L1210 wt leukemia cells are maintained invitro, and they are injected intravenously (1105) into the mice, to develop a systemic metastatic leukemiamodel. The mice are divided into six groups of seven to eight mice each: untreated, treated with squ

19、alenenanoparticles, treated with 100 mg/kg Gemcitabine, treated with 20 mg/kg equivalent SQgemnanoassemblies in Gemcitabine, treated with 100 mg/kg cytarabine, and treated with 100 mg/kg cytarabineevery day for 5 days. After injection of leukemia cells (day 0), all groups of mice received the treatm

20、ent by i.v.injection on days 1, 5, 9, and 14 (i.e., days after injecting leukemia cells), with the exception of the untreatedgroup and the group treated with cytarabine daily by the i.v. route. The mice are monitored regularly forweight differences and survival.MCE has not independently confirmed th

21、e accuracy of these methods. They are for reference only.戶使本產品發表的科研獻 Hepatology. 2019 May;69(5):1995-2012. J Mol Med (Berl). 2019 Jun 14. J Biol Chem. 2017 Jun 2;292(22):9136-9149. Chinese Chemical Letters. 2016 November 11. Biomed Pharmacother. 2019 Sep;117:109185.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Wang H, et al. Enhanced efficacy of Gem