卡奇霉素作用機(jī)制 - Medchemexpress - MCE中國

1、Product Data SheetCalicheamicinCat. No.: HY-19609CAS No.: 108212-75-5分式: CHINOS分量: 1368.35作靶點: DNA Alkylator/Crosslinker; ADC Cytotoxin; Bacterial; Apoptosis作通路: Cell Cycle/DNA Damage; Antibody-drug Conjugate/ADC Related; Anti-infection;Apoptosis儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 mo

2、nths-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 100 mg/mL (73.08 mM)H2O : 0.1 mg/mL (insoluble)* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 0.7308 mL 3.6540 mL 7.3081 mL5 mM 0.1462 mL 0.7308 mL 1.4616 mL10 mM 0.0731 mL 0.3654 mL 0.7308 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；旦配成溶液

3、，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲存時，請在 6 個內(nèi)使，-20C 儲存時，請在 1 個內(nèi)使。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式選擇適當(dāng)?shù)娜芙獍浮Ｒ韵氯芙獍付颊埾劝凑?In Vitro 式配制澄清的儲備液，再依次添加助溶劑：為保證實驗結(jié)果的可靠性，澄 的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的作液，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；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 10% DMSO 40%

4、 PEG300 5% Tween-80 45% salineSolubility: 3 mg/mL (2.19 mM); Clear solution此案可獲得 3 mg/mL (2.19 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 30.0 mg/mL 的澄 DMSO 儲備液加到 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. 請依序添加每種溶劑： 10% DMSO 90% corn oilPage 1 of 2 www.MedChemESolubility: 3 mg/

5、mL (2.19 mM); Clear solution此案可獲得 3 mg/mL (2.19 mM，飽和度未知) 的澄 溶液，此案不適于實驗周 期在半個以上的實驗。以 1 mL 作液為例，取 100 L 30.0 mg/mL 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Calicheamicin種腫瘤抗素，也是有效的細(xì)胞毒性試劑，可引起DNA雙鏈斷裂。Calicheamicin 抑制 DNA 合成。IC & Target Calicheamicins體外研究 PF-06647263 (anti-EFNA4-ADC) is genera

6、ted via conjugation of hE22 lysine residues to the AcButDMH-N-Ac-calicheamicin-1 linker-payload with an average drug-to-antibody ratio (DAR) of 4.6. PF-06647263 elicits antigen-and concentration-dependent cytotoxicity, as exposure to PF-06647263 for 96 hours results in cell death (EC50= appr1 ng/mL)

7、1. CMC-544, consisting of a humanized CD22 Ab linked to calicheamicin, is effective in pediatric primary B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells in vitro. CMC-544 induces cell death in various ALL celllines in a dose- and time-dependent way, with IC50 values ranging from 0.15 t

8、o 4.9 ng/mL. CMC-544 (10 ng/mL) iseffective and specific in primary BCP-ALL cells2. In CMC-544-treated cells, the level of CD22 has decreased relative tothat on G5/44-treated cells and continued to decrease3.體內(nèi)研究 An ADC comprising a humanized anti-EFNA4 monoclonal antibody conjugated to the DNA-dama

9、ging agentcalicheamicin achieves sustained tumor regressions in both TNBC and ovarian cancer PDX in vivo. PF-06647263 (0.27,0.36 mg/kg) results in significant tumor regressions in TNBC xenografts1.PROTOCOLCell Assay 3 The enhancement of the CDC effect is studied in a similar way in the presence of C

10、MC-544 or G5/44. Specifically,after cells are incubated with or without CMC-544 (5 ng/mL calichemicin DMH) or G5/44 at 37C for 2 h, they arewashed three times to remove unbound antibodies. The viability of cells before incubation with CMC-544 is 99.8%.After the cells are re-incubated in CMC-544- and

11、 rituximab-free medium at 37C for 0-48 h, CDC is analyzed.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Cohorts of tumor-bearing mice (140-180 mm3) are randomized into study groups of 6 to 10 based on the number ofAdministration 1 available mic

12、e. The IDBS electronic notebook statistical package, Biobook, is used for automated animalrandomization. Animals are dosed by intraperitoneal injection (or intravenously for 144580) twice a week for 4 cycleswith ADC, or once a week for 2 cycles with 1.5 mg/kg doxorubicin for breast PDX tumors or 5 m

13、g/kg Cisplatin forovarian PDX. Study groups are followed until either individual mice or entire cohort measurements reach 1,200 mm3,at which point sacrifice is indicated. Tumor regression is defined as a reduction in mean tumor volume after dosing.In cases where tumors regress, time to progression (

14、TTP) is determined to be the number of days between the firstdose and the time at which mean tumor volume significantly increase (regrow) after regression.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) PLoS Biol. 2020 Mar 23;18(3):e3000666.

15、Page 2 of 3 www.MedChemE FASEB J. 2018 Jun 6:fj201800092R.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Damelin M, et al. Anti-EFNA4 Calicheamicin Conjugates Effectively Target Triple-Negative Breast and Ovarian Tumor-Initiating Cells to Result inSustained Tumor Re

16、gressions. Clin Cancer Res. 2015 Sep 15;21(18):4165-732. de Vries JF, et al. The novel calicheamicin-conjugated CD22 antibody inotuzumab ozogamicin (CMC-544) effectively kills primary pediatric acutelymphoblastic leukemia cells. Leukemia. 2012 Feb;26(2):255-643. Takeshita A, et al. CMC-544 (inotuzumab ozogamicin), an anti-CD22 immuno-conjugate of calicheamicin, alters the levels of target molecules ofmalignant B-cells. Leukemi