1、Product Data SheetLomustineCat. No.: HY-13669CAS No.: 13010-47-4分式: CHClNO分量: 233.7作靶點: DNA Alkylator/Crosslinker; Autophagy; Apoptosis作通路: Cell Cycle/DNA Damage; Autophagy; Apoptosis儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數據體外實驗 DMSO : 100 mg/mL (427.90 mM)* means s

2、oluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 4.2790 mL 21.3950 mL 42.7899 mL5 mM 0.8558 mL 4.2790 mL 8.5580 mL10 mM 0.4279 mL 2.1395 mL 4.2790 mL請根據產品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；旦配成溶液，請分裝保存，避免反復凍融造成的產品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲存時，請在 6 個內使，-20C 儲存

3、時，請在 1 個內使。體內實驗請根據您的實驗動物和給藥式選擇適當的溶解案。以下溶解案都請先按照 In Vitro 式配制澄清的儲備液，再依次添加助溶劑：為保證實驗結果的可靠性，澄 的儲備液可以根據儲存條件，適當保存；體內實驗的作液，建議您現現配，當天使； 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沉淀、析出現象，可以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (10.70 mM); Clear solution此案可獲得 2.5

4、 mg/mL (10.70 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；然后繼續加 450 L 理鹽定容 1 mL。2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (10.70 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (10.70 mM，飽和度未知) 的澄清

5、溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (10.70 mM); Clear solution此案可獲得 2.5 mg/mL (10.70 mM，飽和度未知) 的澄 溶液，此案不適于實驗周 期在半個以上的實驗。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性

6、 Lomustine (CCNU; NSC 79037)種 DNA 烷化劑 (DNA alkylator)，具有抗腫瘤活性。IC & Target DNA Alkylator1體外研究 Lomustine (CCNU; NSC 79037) is a DNA alkylating agent. Lomustine (CCNU, 0-250 M) is cytotoxic to the U87-MGcells expressing tumor-derived mutant IDH1, and has little effect on the expression of wild-type IDH

7、1. Thecombination of Lomustine and procarbazine or vincristine has no additive effect on the killing of cells expressingmutant or wild-type IDH1. Moreover, overexpression of either ALKBH2 or ALKBH3 partially reduces the death HT1080cells exposed to Lomustine1. Lomustine (CCNU) suppresses U87-MG grow

8、th with an ED50 of 68.1 M. Lomustine(CCNU) (30, 40 M) in combination with docosahexaenoic acid (DHA) darmatically inhibits 2 additional human-derived glioblastoma cell lines, and induces U87-MG apoptosis and necrosis. Lomustine (30 M) causes G2/M arrest2. Lomustine (CCNU) reduces the viability of F9

9、8 rat orthotopic glioma cells and Tu-2449 mouse glioma cell line, withIC50s of 20.8 M and 18.6 M, respectively3.體內研究 Lomustine (CCNU; NSC 79037) (30 mg/kg) in combination with Toca 511 + 5-FC prolongs survival in rats bearing F98tumor cells. Lomustine (CCNU) (30 mg/kg) combined with Toca-511 + 5-FC

10、also exhibits antitumor activity in theB6C3F1 mice bearing Tu-2449 glioma cells3.PROTOCOLCell Assay 2 Initially, cells (5000 cells/well) are cultured in 96-well flat-bottom plates overnight in complete medium to establish alinear growth rate. Spent medium is replaced with new medium supplemented wit

11、h 2% FBS and varying treatments(100 L total volume/well). Ethanol-supplemented cells ( 0.5%) serve as the vehicle control. Cells are maintained at37C in 5% CO2 in a humidified atmosphere for 24 hours prior to assessment of cell growth with the WST-1 assayreagent. Medium alone combined with the WST-1

12、 assay reagent establishes nonspecific values that are subtractedfrom the experimental optical density (OD) readings (OD at 450 nm). Vehicle control OD readings serve as standardproliferative potential normalized to 100%. The proliferation index is calculated by dividing the average OD treatmentread

13、ing by the average OD vehicle reading and multiplying by 1002.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice3Administration 3 Groups of B6C3F1 mice receive PBS or 5-FC only as a control during the study (n = 8 per group). One group of mice

14、(Lomustine Day 1 + PBS) receive one dose of Lomustine (30 mg/kg) on day 1 and a total of six cycles of PBS (800 L/day, BID for 4 consecutive days every 10 days). The rest of the mice receive 5-FC (500 mg/kg/dose, IP, BID) for 4consecutive days, plus Lomustine at day 1 (Lomustine (CCNU) Day 1 + 5-FC)

15、 or day 43 (Lomustine (CCNU) Day 43 +5-FC). Cycles of 4-days on, 10-days off 5-FC or PBS are repeated a total of 6 times. Each experiment is terminated atthe end of the last 5-FC treatment. All tissues are collected and saved for histopathology. Toxicity in groups receivingPage 2 of 3 www.MedChemELo

16、mustine is compared to the groups receiving PBS or 5-FC alone or in combination with 5-FC at designated timepoints3.Rats3Groups of rats receive PBS or 5-FC only as controls during the study (n = 8 per group). One group of rats (Lomustine(CCNU) Day 1 + PBS) receive one dose of Lomustine (30 mg/kg) at

17、 day 1 and a total of six cycles of PBS (8 mL/day,BID). The rest of the rats receive 5-FC (500 mg/kg/dose, IP, BID) for 5 consecutive days, followed by 2 days off drug,plus Lomustine on day 1 (Lomustine (CCNU) Day 1 + 5-FC) or day 22 (Lomustine (CCNU) Day 22 + 5-FC). Cycles of5-days on, 2-days off 5

18、-FC or PBS are repeated a total of 6 times3.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產品發表的科研獻 J Mol Med (Berl). 2019 Aug;97(8):1183-1193. Acta Pharmacol Sin. 2020 May 12. Mol Imaging Biol. 2019 Apr 15.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Wang P, et al. Oncometabolite D-2-Hydroxyglutarate Inhibits ALKBH DNA Repair Enzymes and Sensitizes IDH Mutant Cells to Alkylating Agents. CellRep. 2015 Dec 22;13(11):2353-2361.