Pemetrexed disodium

製品コードS1135 バッチS113506

印刷

化学情報

Chemical Structure Synonyms LY-231514 disodium Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C20H19N5Na2O6
分子量 471.37 CAS No. 150399-23-8
Solubility (25°C)* 体外 Water 94 mg/mL (199.41 mM)
DMSO Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Pemetrexed disodium is a novel antifolate and antimetabolite for TS, DHFR and GARFT with Ki of 1.3 nM, 7.2 nM and 65 nM in cell-free assays, respectively. Pemetrexed induces autophagy and apoptosis.
in vitro Pemetrexed disodium shows the antiproliferative activity in CCRF-CEM leukemia, GC3/C1 colon carcinoma, and HCT-8 ileocecal carcinoma cells with IC50 of 25 nM, 34 nM and 220 nM, respectively. [1] A recent study shows that cisplatin plus Pemetrexed combined with SOCS-1 gene delivery shows the antitumor effect by inhibition of cell proliferation, invasiveness, and induction of apoptosis in MPM cells infected with adenovirus-expressing SOCS-1 vector. [2]
in vivo In the human H460 non-small cell lung carcinoma xenograft, Pemetrexed disodium produces a duration-dependent tumor growth delay (TGD). [3]

プロトコル(参考用のみ)

キナーゼアッセイ Enzyme Assays and Methods.
TS activity is assayed using a spectrophotometric method, which involved monitoring the increase in absorbance at 340 nm resulting from formation of the product, 7,8-dihydrofolate. The assay buffer contains 50 mM N-tris[hydroxymethyljmethyl-2-aminoethanesulfonic acid, 25 mM MgC12, 6.5 mM formaldehyde, 1 mM EDTA, and 75 mM 2-mercaptoethanol, pH 7.4. The concentrations of deoxyuridylate monophosphate, 6R-MTHF, and hIS are 100 μM, 30μM and 30 nM (1.7 milliunits/mL), respectively. At the 6R-MTHF concentration, an uninhibited reaction and six concentrations of inhibitor are assayed. Ki app values are determined by fitting the data to the Morrison equation using nonlinear regression analysis with the aid of the program ENZFITTER. Ki values are calculated using the equation: Ki app= Ki(1 + [S]/Km), where [S] is equal to 30 μM and Km is equal to 3 μM. DHFR activity is assayed spectrophotometrically by monitoring the dis appearance of the substrates NADPH and 7,8-dihydrofolate at 340 nm. The reaction takes place at 25°C in 0.5 mL of 50 mM potassium phosphate buffer, which contains 150 mM KC1 and 10 nM 2-mercaptoethanol, pH 7.5, and 14 nM (0.34 milliunitlmL) DHFR. The NADPH concentration is 10 μM and 7,8-dihydrofolate is varied at 5, 10, or 15 μM. At each 7,8-dihydrofolate concentration, an uninhibited reaction and seven concentrations of inhibitor are assayed. The ENZFITI'ER microcomputer program is used to obtain Ki app values by fitting the data to the Morrison equation by nonlinear regression analysis. Ki app= Ki(1 + [S]/Km), where [S] is equal to the concentration of 7,8-dihydrofolate used and Km of 7,8-dihydrofolate is equal to 0.15 μM. GARFT activity is assayed spectrophotometrically by monitoring the increase of absorbance resulting from formation of the product 5,8-dideazafolate at 295 nm. The reaction solvent contains 75 mM HEPES, 20% glycerol, and 50 mM a-thioglygerol, pH 7.5, at 25°C. The concentrations of substrates and enzyme used are 10 μM α,β-glycinamide ribonucleotide, 0-10 μM 10-formyl-5,8-dideazafolic acid, and 10 nM (1.9 milliunits/mL) GARFT. Ki values are calculated using the Enzyme Mechanism program of the Beckman DU640 spectrophotometer, which uses nonlinear regression analysis to fit data to the Michaelis-Menten equation for competitive inhibition.
細胞アッセイ 細胞株 CCRF-CEM leukemia, GC3/C1 colon carcinoma, and HCT-8 ileocecal carcinoma cells.
濃度 0-30 μM
反応時間 72 hours
実験の流れ Dose-response curves are generated to determine the concentration required for 50% inhibition of growth (IC50). Pemetrexed disodium is dissolved initially in DMSO at a concentration of 4 mg/mL and further diluted with cell culture medium to the desired concentration. CCRF-CEM leukemia cells in complete medium are added to 24-well Cluster plates in a total volume of 2.0 mL. Pemetrexed disodium at various concentrations are added to duplicate wells so that the final volume of DMSO is 0.5%. The plates are incubated for 72 hour at 37 °C in an atmosphere of 5% CO2 in air. At the end of the incubation, cell numbers are determined on a ZBI Coulter counter. For several studies, IC50s are determined for each compound in the presence of either 300 μM AICA, 5 μM thymidine, 100 μM hypoxanthine, or combination of 5 μM hymidine plus 100 μM hypoxanthine. For adherent tumor cells, a modification of the original MTT colorimetric assay is used to measure cell cytotoxicity. The human tumor cells are seeded in 100 μL assay medium/well in 96-well flat-bottomed tissue culture plates. The assay medium contains folic acid-free RPMI 1640 supplemented with 10% FCS and either 2 nM folinic acid or 2.3 μM folic acid as the sole folate source. Well 1A is left blank. Stock solutions of antifolates are prepared in Dulbecco's PBS at 1 mg/mL, and a series of 2-fold dilutions are subsequently made in PBS. Ten-μL aliquots of each concentration are added to triplicate wells. Plates are incubated for 72 hours at 37 °C in a humidified atmosphere of 5% CO2-in-air. MTT is dissolved in PBS at 5 mg/mL, 10 μL of stock MTF solution are added to each well of an assay, and the plates are incubated at 37 °C for 2 additional hours. Following incubation, 100 μL of DMSO are added to each well. After thorough formazan solubilization, the plates are read on a Dynatech MR600 reader, using a test wavelength of 570 nm and a reference wavelength of 630 nm. The IC50 is determined as the concentration of drug required to inhibit cell growth by 50% compared to an untreated controls.
動物実験 動物モデル EMT-6 mammary carcinoma, the human HCT 116 colon carcinoma, and the human H460 non-small cell lung carcinoma are injected s.c. into the nude mice.
投薬量 100 mg/kg or 150 mg/kg
投与方法 Administered via i.p.

カスタマーフィードバック

Data from [Data independently produced by Cancer Res, 2014, 74(21), 5948-54]

Data from [Data independently produced by Biochem Biophys Res Commun, 2014, 452(1), 72-8]

Data from [Data independently produced by Mol Cancer Ther, 2013, 12, 2675-84]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

MPS1 inhibition primes immunogenicity of KRAS-LKB1 mutant lung cancer [ Cancer Cell, 2022, 40(10):1128-1144.e8] PubMed: 36150391
CDK/cyclin dependencies define extreme cancer cell-cycle heterogeneity and collateral vulnerabilities [ Cell Rep, 2022, 38(9):110448] PubMed: 35235778
Establishment and large-scale validation of a three-dimensional tumor model on an array chip for anticancer drug evaluation [ Front Pharmacol, 2022, 13:1032975] PubMed: 36313330
A study of protein-drug interaction based on solvent-induced protein aggregation by fluorescence correlation spectroscopy [ Analyst, 2022, 10.1039/d2an00031h] PubMed: 35253833
The novel mechanism of Med12-mediated drug resistance in a TGFBR2-independent manner [ Biochem Biophys Res Commun, 2022, 610:1-7] PubMed: 35461070
A Novel Molecular Target in EGFR-mutant Lung Cancer Treated With the Combination of Osimertinib and Pemetrexed [ Anticancer Res, 2022, 42(2):709-722] PubMed: 35093869
Arachidonic acid drives adaptive responses to chemotherapy-induced stress in malignant mesothelioma [ J Exp Clin Cancer Res, 2021, 40(1):344] PubMed: 34727953
Essential role of the histone lysine demethylase KDM4A in the biology of malignant pleural mesothelioma (MPM) [ Br J Cancer, 2021, 10.1038/s41416-021-01441-7] PubMed: 34088988
An antibody-based proximity labeling map reveals mechanisms of SARS-CoV-2 inhibition of antiviral immunity [ Cell Chem Biol, 2021, S2451-9456(21)00442-6] PubMed: 34672954
Osimertinib-resistant NSCLC cells activate ERBB2 and YAP/TAZ and are killed by neratinib [ Biochem Pharmacol, 2021, 190:114642] PubMed: 34077739

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人間や獣医の診断であるか治療的な使用のためにでない。

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