鹽酸苯達(dá)莫司汀作用機(jī)制 - Medchemexpress - MCE中國(guó)

1、Product Data SheetBendamustine hydrochlorideCat. No.: HY-B0077CAS No.: 3543-75-7分式: CHClNO分量: 394.72作靶點(diǎn): DNA Alkylator/Crosslinker; Apoptosis作通路: Cell Cycle/DNA Damage; Apoptosis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) DMSO : 100 mg/mL (25

2、3.34 mM; Need ultrasonic)SolventMass1 mg 5 mg 10 mgConcentration制備儲(chǔ)備液1 mM 2.5334 mL 12.6672 mL 25.3344 mL5 mM 0.5067 mL 2.5334 mL 5.0669 mL10 mM 0.2533 mL 1.2667 mL 2.5334 mL請(qǐng)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(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)

3、在 6 個(gè)內(nèi)使，-20C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都?qǐng)先按照 In Vitro 式配制澄清的儲(chǔ)備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的式助溶1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.33 mM); Clear sol

4、ution此案可獲得 2.5 mg/mL (6.33 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(chǔ)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(xù)加 450 L 理鹽定容 1 mL。2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.33 mM); Clear solution此案可獲得 2.5 mg/mL (6.33 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為

5、例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。Page 1 of 2 www.MedChemE3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (6.33 mM); Clear solution此案可獲得 2.5 mg/mL (6.33 mM，飽和度未知) 的澄 溶液，此案不適于實(shí)驗(yàn)周 期在半個(gè)以上的實(shí)驗(yàn)。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 油中，混合均勻。BIOLOGICAL AC

6、TIVITY物活性 Bendamustine hydrochloride作。種 DNA 交聯(lián)劑 (DNA crosslinker)，能夠?qū)е?DNA 斷裂，具有烷基化和抗代謝物的IC & Target DNA Alkylator/Crosslinker1體外研究 Bendamustine hydrochloride is a DNA cross-linking agent that causes DNA breaks, with alkylating and antimetaboliteproperties. Bendamustine uniquely regulates apoptosis

7、pathways and DNA repair pathways in non-Hodgkinslymphoma cells. Bendamustine (50 M) induces p21 (Cip1/Waf1) and NOXA genes, and increases the expression ofp53 in SU-DHL-1 cells. Bendamustine (25 M) blocks mitotic checkpoints and cuases mitotic catastrophe1.Bendamustine reduces the viability of multi

8、ple myeloma (MM) cell lines, such as RPMI-8226 and 8226-LR5 cells, withIC25s of 101.8 and 585.5 M after 24 h incubation, and 51.7 and 374.3 M after 48 h incubation, respectively.Bendamustine induces a specific caspase-dependent MM cell death and inhibits the spindle-assembly checkpoint2.體內(nèi)研究 Bendamu

9、stine (25 mg/kg, i.v.) shows potent inhibition on the growth of tumor cells by 91%, 99% and 95% for DoHH-2, Granta 519 and RAMOS models, respectively. Moreover, the antitumor effect of Bendamustine is enhanced by rituximab in DoHH-2 and RAMOS models, but not in Granta 519 model3.PROTOCOLCell Assay 2

10、 Cytotoxicity of both Bendamustine and melphalan on multiple myeloma (MM) cells is calculated as inhibition of cellviability by measuring the percentage of cell survival by MTS assay. Briefly, cells (1 104/well) are seeded in 96-wellplates with increasing concentrations of the drug and analyzed afte

11、r 24, 48, 72 and 96 h of incubation. To this end, 1g/mL of MTS solution is added to each well and, after 1 h at 37 C, the dark blue formazan crystals are dissolved byisopropanol 1 N and HCl (24:1, vol/vol). Finally, the absorbance is measured at 490 nm in a 96-well plate reader. Cellsurvival is esti

12、mated as the percentage of the absorbance of untreated controls and each test is performed intriplicate. The inhibitory concentrations 50 (IC50) and 25 (IC25) of each drug, being the amount able to reduce cellgrowth to 50% and 25%, respectively, of that of untreated control cells, are calculated, an

13、d the tests are performed inparallel using equitoxic concentrations of Bendamustine and melphalan. The relative resistance index (RRI) isexpressed as the ratio of the IC50 of 8226-LR5 to the IC50 of RPMI-8226 cells2.MCE has not independently confirmed the accuracy of these methods. They are for refe

14、rence only.Animal Mice3Administration 3 C.B.-17 scid mice (DoHH-2, Granta 519) or C.B.-17 scid-bg mice (SuDHL-4, RAMOS) are inoculated with 1 106 (DoHH-2, RAMOS), 3 106 (SuDHL-4) or 5 106 (Granta 519) cells s.c. in the right flank. For flank xenografts,inoculation volume is 0.2 mL consisting of a 50

15、:50 mixture of cells in growth medium and Matrigel. Tumour volume isestimated by two to three weekly measurements of the length and width of the tumour by electronic calipers andapplying the following equation: V=LW2/2. Tumours are allowed to reach approximately 250 mm3, and mice aresize-matched (da

16、y 0) into treatment and control groups. For systemic Granta 519 tumour models, 2 106 cells areinjected via the tail vein in 0.1 mL volume of cell medium on day 0, and treatment is initiated on day 14. All animalsare ear-tagged and monitored individually throughout the experiment. Navitoclax is admin

17、istered by oral gavagePage 2 of 3 www.MedChemEonce daily in a mixture of Phosal 50PG : PEG400 : ethanol. Bendamustine and rituximab are administered i.v. at 25mg/kg and 10 mg/kg, respectively, on day 1. Navitoclax is administered approximately 2 h before Bendamustine andrituximab. All trials are com

18、prised of 10 mice per group. Mice are humanely killed when tumours reach a size 2000mm3 or when any signs of distress are monitored. Signs of distress include loss of ambulation, laboured breathing orweight loss 20% mean body weight per cage3.MCE has not independently confirmed the accuracy of these

19、 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 Aug;97(8):1183-1193. J Biomed Res. 2017 0(0): 1-12. Patent. US20160222465A1.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Leoni LM, et al. Bendamustine (Treanda) displays a distinct pattern of cytotoxicity and unique mechanistic features compared with other alkylatingagents. Clin Cancer Res. 2008 Jan 1;14(1):309-17.2. Cives M, et al. Bendamustine overcomes resistance to melphalan in myeloma