奧沙利鉑作用機(jī)制 - Medchemexpress - MCE中國

1、Product Data SheetOxaliplatinCat. No.: HY-17371CAS No.: 61825-94-3分式: CHNOPt分量: 397.29作靶點(diǎn): DNA Alkylator/Crosslinker; Autophagy作通路: Cell Cycle/DNA Damage; Autophagy儲(chǔ)存式: 4C, protect from light* In solvent : -80C, 6 months; -20C, 1 month (protect from light)溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMF : 4 mg/mL (10.07 mM; Need ultr

2、asonic; DMSO can inactivate Oxaliplatins activity)H2O : 1.7 mg/mL (4.28 mM; Need ultrasonic and warming; DMSO can inactivate Oxaliplatins activity)SolventMass1 mg 5 mg 10 mgConcentration制備儲(chǔ)備液1 mM 2.5171 mL 12.5853 mL 25.1705 mL5 mM 0.5034 mL 2.5171 mL 5.0341 mL10 mM 0.2517 mL 1.2585 mL 2.5171 mL請(qǐng)根據(jù)產(chǎn)

3、品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存式和期限：-80C, 6 months; -20C, 1 month (protect from light)。-80C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)內(nèi)使，-20C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)內(nèi)使。BIOLOGICAL ACTIVITY物活性 Oxaliplatin種 DNA 合成 抑制劑。Oxaliplatin 會(huì)導(dǎo)致 DNA 交聯(lián)損傷，阻 DNA 復(fù)制和轉(zhuǎn)錄并導(dǎo)致細(xì)胞死亡。Oxaliplatin 以時(shí)間依賴式抑制素瘤細(xì)胞系 C32 和 G361，IC50 值分別為 0.98 M 和 0.14

4、M。Oxaliplatin 可以誘導(dǎo)細(xì)胞噬 (autophagy)。IC & Target IC50: DNA synthesis1體外研究 Oxaliplatin acts through the formation of DNA-adducts. Oxaliplatin induces primary and secondary DNA lesionsleading to cell apoptosis1. Oxaliplatin inhibits human melanoma cell lines C32 and G361 with IC50 values of 0.98 Mand 0.1

5、4 M, respectively2. Oxaliplatin potently inhibits bladder carcinoma cell lines RT4 and TCCSUP, ovariancarcinoma cell line A2780, colon carcinoma cell line HT-29, glioblastoma cell lines U-373MG and U-87MG, andmelanoma cell lines SK-MEL-2 and HT-144 with IC50 of 11 M, 15 M, 0.17 M, 0.97 M, 2.95 M, 17

6、.6 M, 30.9 Mand 7.85 M, respectively3.Page 1 of 2 www.MedChemE體內(nèi)研究 Oxaliplatin (10 mg/kg, i.p.) significantly reduces tumor volume and apoptotic index in the nude mice bearinghepatocellular HCCLM3 tumors4. Oxaliplatin (5 mg/kg, i.v.) is effective on T-leukemia-lymphoma L40 AKR with T/C of1.77. Oxali

7、platin is efficient on intracerebrally grafted L1210 leukemia, MA 16-C xenografts, B16 melanomaxenografts, Lewis lung xenografts and C26 colon carcinoma xenografts5. Oxaliplatin induces impairment ofretrograde neuronal transport in mice6.PROTOCOLCell Assay 3 Typically, cells are plated into 96-well

8、plates on day 0 and exposed to Oxaliplatin on day 1; the sulforhodamine-Bassay is carried out 48 h after Oxaliplatin exposure. The plates are incubated at 37C in 5% CO2 and 100% relativehumidity at all times except when adding Oxaliplatin and during the final assay period. The initial number of cell

9、splated for the assay ranged from 2-20103 cells/50/nL/well. The numbers of cells for plating and the drug exposuretime are based on pilot studies using the criteria that (a) the cells in control wells are still in the log phase of growthon the day of the assay; (b) the maximum absorbance for the unt

10、reated controls on the day of the assay is in therange of 1.0 to 1.5; and (c) cells go through 2 doublings during the drug exposure. Eight wells are used perconcentration. The plates are read at 570 and/or 540 nm using a Biotek Instruments model EL309 microplate readerinterfaced with an IBM PC-compa

11、tible computer.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal HCC tumor models produced by HCCLM3 are established in nude mice by subcutaneous injection of 5105 HCCLM3Administration 4 cells in 0.2 mL of serum-free culture medium into the left up

12、per flank region. Three days later, the mice are randomLyassigned to receive one of the following three treatments: i) a weekly intraperitoneal (i.p.) injection of distilled water(control group, n=8); ii) a weekly i.p. injection of oxaliplatin at 5 mg/kg (low dose group, n=7); or iii) a weekly i.p.i

13、njection of oxaliplatin at 10 mg/kg (high dose group, n=7). Tumor growth is monitored by measuring two bisectingdiameters of each tumor with a caliper every 5 days. The tumor volume is calculated using the formula (V=ab2/2),with a as the larger diameter and b as the smaller diameter. Mice are euthan

14、ized by day 32 after oxaliplatinadministration. Tumors of each group are completely removed, weighed, photographed, and fixed in 10%formalin/PBS or stored in liquid nitrogen for histological examination.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使

15、本產(chǎn)品發(fā)表的科研獻(xiàn) Nat Med. 2019 Sep;25(9):1428-1441. J Exp Med. 2018 Jan 2;215(1):115-140. Proc Natl Acad Sci U S A. 2017 Mar 7;114(10):E1825-E1832. Cancer Res. 2018 Oct 1;78(19):5586-5599. Cancer Lett. 2020 Feb 12. pii: S0304-3835(20)30069-0.See more customer validations on HYPERLINK www.MedChemE www.MedCh

16、emEREFERENCES1. Raymond E, et al. Oxaliplatin: a review of preclinical and clinical studies. Ann Oncol. 1998 Oct;9(10):1053-71.2. Mohammed MQ, et al. Oxaliplatin is active in vitro against human melanoma cell lines: comparison with cisplatin and carboplatin. Anticancer Drugs.2000 Nov;11(10):859-63.P

17、age 2 of 3 www.MedChemE3. Pendyala L, et al. In vitro cytotoxicity, protein binding, red blood cell partitioning, and biotransformation of oxaliplatin. Cancer Res. 1993 Dec15;53(24):5970-6.4. Wang Z, et al. Oxaliplatin induces apoptosis in hepatocellular carcinoma cells and inhibits tumor growth. Ex

18、pert Opin Investig Drugs. 2009Nov;18(11):1595-6045. Math G, et al. Oxalato-platinum or 1-OHP, a third-generation platinum complex: an experimental and clinical appraisal and preliminary comparisonwith cis-platinum and carboplatinum. Biomed Pharmacother. 1989;43(4):237-50.6. Schellingerhout D, et al. Impairment of retrograde neur