Lomustine-CCNU-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemELomustineCat. No.: HY-13669CAS No.: 13010-47-4Synonyms: CCNU; NSC 79037分式: CHClNO分量: 233.7作靶點: DNA Alkylator/Crosslinker; Autophagy作通路: Cell Cycle/DNA Damage; Autophagy儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-2

2、0C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 100 mg/mL (427.90 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration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(jù)產(chǎn)品在不同溶劑中的溶解度，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。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式

3、選擇適當(dāng)?shù)娜芙獍?，配制前請先配制澄清的儲備液，再依次添加助溶?為保證實驗結(jié)果的可靠性，體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲備液可以根據(jù)儲存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：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 solution2. 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); Cle

4、ar solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (10.70 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Lomustine (CCNU)種 DNA 烷化劑 (DNA alkylator)，具有抗腫瘤活性。IC50 & Target DNA Alkylator 1體外研究 Lomustine (CCNU) is a DNA alkylating agent. Lomust

5、ine (CCNU, 0-250 M) is cytotoxic to the U87-MG cellsexpressing tumor-derived mutant IDH1, and has little effect on the expression of wild-type IDH1. Thecombination of Lomustine and procarbazine or vincristine has no additive effect on the killing of cellsexpressing mutant or wild-type IDH1. Moreover

6、, overexpression of either ALKBH2 or ALKBH3 partiallyreduces the death HT1080 cells exposed to Lomustine 1. Lomustine (CCNU) suppresses U87-MG growthwith an ED50 of 68.1 M. Lomustine (CCNU) (30, 40 M) in combination with docosahexaenoic acid (DHA)darmatically inhibits 2 additional human-derived glio

7、blastoma cell lines, and induces U87-MG apoptosis andnecrosis. Lomustine (30 M) causes G2/M arrest 2. Lomustine (CCNU) reduces the viability of F98 ratorthotopic glioma cells and Tu-2449 mouse glioma cell line, with IC50s of 20.8 M and 18.6 M, respectively3.體內(nèi)研究 Lomustine (CCNU) (30 mg/kg) in combin

8、ation with Toca 511 + 5-FC prolongs survival in rats bearing F98tumor cells. Lomustine (CCNU) (30 mg/kg) combined with Toca-511 + 5-FC also exhibits antitumor activity inthe B6C3F1 mice bearing Tu-2449 glioma cells 3.PROTOCOLCell Assay 2 Initially, cells (5000 cells/well) are cultured in 96-well fla

9、t-bottom plates overnight in complete medium toestablish a linear growth rate. Spent medium is replaced with new medium supplemented with 2% FBS andvarying treatments (100 L total volume/well). Ethanol-supplemented cells (2 in a humidified atmosphere for24 hours prior to assessment of cell growth wi

10、th the WST-1 assay reagent. Medium alone combined with theWST-1 assay reagent establishes nonspecific values that are subtracted from the experimental opticaldensity (OD) readings (OD at 450 nm). Vehicle control OD readings serve as standard proliferative potentialnormalized to 100%. The proliferati

11、on index is calculated by dividing the average OD treatment reading bythe average OD vehicle reading and multiplying by 100 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 3Administration 3 Groups of B6C3F1 mice receive PBS or 5-FC only as

12、 a control during the study (n = 8 per group). One groupof mice (Lomustine Day 1 + PBS) receive one dose of Lomustine (30 mg/kg) on day 1 and a total of sixcycles 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 4 consecutiv

13、e days, plus Lomustine at day 1 (Lomustine (CCNU) Day 1 + 5-FC) or day 43 (Lomustine (CCNU) Day 43 + 5-FC). Cycles of 4-days on, 10-days off 5-FC or PBS are2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemErepeated a total of 6 times. Each experiment is terminated at the end of the last 5-FC treatmen

14、t. All tissuesare collected and saved for histopathology. Toxicity in groups receiving Lomustine is compared to the groupsreceiving PBS or 5-FC alone or in combination with 5-FC at designated time points 3.Rats 3Groups of rats receive PBS or 5-FC only as controls during the study (n = 8 per group).

15、One group of rats(Lomustine (CCNU) Day 1 + PBS) receive one dose of Lomustine (30 mg/kg) at day 1 and a total of sixcycles of PBS (8 mL/day, BID). The rest of the rats receive 5-FC (500 mg/kg/dose, IP, BID) for 5 consecutivedays, followed by 2 days off drug, plus Lomustine on day 1 (Lomustine (CCNU)

16、 Day 1 + 5-FC) or day 22(Lomustine (CCNU) Day 22 + 5-FC). Cycles of 5-days on, 2-days off 5-FC or PBS are repeated a total of 6times 3.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) J Mol Med (Berl). 2019 Jun 14. Mol Imaging Biol. 2019 Apr

17、15.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Wang P, et al. Oncometabolite D-2-Hydroxyglutarate Inhibits ALKBH DNA Repair Enzymes and Sensitizes IDH Mutant Cells toAlkylating Agents. Cell Rep. 2015 Dec 22;13(11):2353-2361.2. Harvey KA, et al. Enhanced anticancer properties of lomustine in conjunction with docosahexaenoic acid in glioblastoma cell lines. JNeurosurg. 2015 Mar;122(3):547-56.3. Yagiz K, et al. Toca 511 plus 5-fluorocytosine in combination with lomustine shows chemotoxic and immunotherapeutic activity with noadditive toxicity