Temozolomide-NSC-362856-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETemozolomideCat. No.: HY-17364CAS No.: 85622-93-1Synonyms: NSC 362856; CCRG 81045; TMZ分式: CHNO分量: 194.15作靶點: Autophagy; DNA Alkylator/Crosslinker作通路: Autophagy; Cell Cycle/DNA Damage儲存式: -20C, stored under nitrogen* In solvent :

2、 -80C, 6 months; -20C, 1 month (stored undernitrogen)溶解性數(shù)據(jù)體外實驗 DMSO : 20.83 mg/mL (107.29 mM; Need ultrasonic)H2O : 2.86 mg/mL (14.73 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 5.1507 mL 25.7533 mL 51.5066 mL5 mM 1.0301 mL 5.1507 mL 10.3013 mL10 mM 0.5151 mL 2.5753 mL 5.1

3、507 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選擇適當?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，當天使；澄清的儲備液可以根據(jù)儲存條件，適當保存；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: 2.08 mg/mL (10.71 mM); Clear solution2. 請依序添加每種溶劑： 10%

4、DMSO 90% (20% SBE-CD in saline)Solubility: 2.08 mg/mL (10.71 mM); Clear solution3. 請依序添加每種溶劑： 10% DMSO 90% corn oil1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemESolubility: 2.08 mg/mL (10.71 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Temozolomide (NSC 362856; CCRG 81045)可服的于治療某些腦癌的DNA烷基化劑。IC50 & T

5、arget DNA alkylator 1體外研究 Temozolomide (TZM) is a methylating agent that crosses the blood-brain barrier and is indicated formalignant gliomas and metastatic melanomas. Temozolomide is effective against tumor cells that arecharacterized by low levels of O6-alkylguanine DNA alkyltransferase (OGAT) an

6、d a functional mismatchrepair system (MR) 1. Determination of the IC50 for Temozolomide (TZM) in different cell lines gave valuesranging from 14.1 to 234.6 M that fell into two clearly differentiated groups: cell lines with low IC50 values(50 values (100 M), which include SF268 (147.22.1 M) and SK-N

7、-SH cells (234.62.3 M) 2.體內(nèi)研究 Temozolomide (TZM), as a single agent, does not significantly increase mdian survival time (MST) withrespect to control. Noteworthy, intracranial injection of NU1025, immediately before the administration of 100or 200 mg/kg Temozolomide, significantly increases lifespan

8、s with respect to controls or to groups treatedwith Temozolomide only. When Temozolomide is fractionated, the increase in lifespan (ILS) obtained withthis schedule is higher than that observed when NU1025 is combined with a single injection ofTemozolomide (statistical comparison of survival curves:

9、NU1025 intracranially+Temozolomide 100 mg/kg2vs NU1025+Temozolomide 200 mg/kg; P=0.023) 1.PROTOCOLCell Assay 1 The murine lymphoma cell line L5178Y of DBA/2 (H-2d/H-2d) origin is cultured in RPMI-1640 containing 10%fetal calf serum and antibiotics. Inhibition of PARP is obtained by treating cells (1

10、05 cells/mL) with 8-hydroxy-2-methylquinazolin-43H-1 (NU1025), at a concentration (25 M) that abrogates PARP activity. Cells arethen exposed to Temozolomide (7.5-125 M) and are cultured for 3 days. Cell growth is evaluated bycounting viable cells in quadruplicate, and apoptosis is assessed by flow c

11、ytometry analysis of DNA content.Long-term survival is analyzed by colony-formation assay 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 1 Male B6D2F1 (C57BL/6DBA/2) mice are anesthetized with ketamine (100 mg/kg) and xyla

12、zine (5 mg/kg) in0.9% NaCl solution (10 mL/kg intraperitoneally). L5178Y cells (104 in 0.03 mL RPMI-1640) are then injectedintracranially, through the center-middle area of the frontal bone to a 2-mm depth, using a 0.1-mL glassmicrosyringe and a 27-gauge disposable needle. To evaluate tumor cell gro

13、wth, brains are fixed in 10%phosphate-buffered formaldehyde, and histologic sections (5 m) are cut along the axial plane, stained withhematoxylin-eosin, and analyzed by light microscopy. Temozolomide is dissolved in DMSO (40 mg/mL),diluted in saline (5 mg/mL), and administered intraperitoneally on d

14、ay 2 after tumor injection at 100 mg/kg or200 mg/kg, doses commonly used for in vivo preclinical studies. Because cytotoxicity induced by2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemETemozolomide and PARP inhibitors can be improved by fractionated modality of treatment, in selectedgroups a total

15、dose of 200 mg/kg Temozolomide is divided in 2 doses of 100 mg/kg given on days 2 and 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 J Pineal Res. 2016 Sep;61(2):208-17. Neuro Oncol. 2019 Jun 21. pii: noz107 Cell Physiol Biochem. 2018;48(

16、4):1694-1702. Cell Physiol Biochem. 2018;45(2):819-831. J Mol Med (Berl). 2019 Jun 14.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Tentori L, et al. Combined treatment with temozolomide and poly(ADP-ribose) polymerase inhibitor enhances survival of mice bearinghematologic malignancy at the central nervous system site. Blood. 2002 Mar 15;99(6):2241-4.2. Perazzoli G, et al. Temozolomide Resistance in Glioblastoma Cell Lines: Implication of MGMT, MMR, P-Glycoprotein and CD1