Calicheamicin |
| Catalog No.GC19086 |
Calicheamicin is a cytotoxic agent that causes double-strand DNA breaks.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 108212-75-5
Sample solution is provided at 25 µL, 10mM.
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Calicheamicin is a cytotoxic agent that causes double-strand DNA breaks.
PF-06647263 (anti-EFNA4-ADC) is generated via conjugation of hE22 lysine residues to the AcButDMH-N-Ac-calicheamicin-γ1 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= appr 1 ng/mL)[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 cell lines in a dose- and time-dependent way, with IC50 values ranging from 0.15 to 4.9 ng/mL. CMC-544 (10 ng/mL) is effective and specific in primary BCP-ALL cells[2]. In CMC-544-treated cells, the level of CD22 has decreased relative to that on G5/44-treated cells and continued to decrease[3].
An ADC comprising a humanized anti-EFNA4 monoclonal antibody conjugated to the DNA-damaging agent calicheamicin 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 xenografts[1].
References:
[1]. Damelin M, et al. Anti-EFNA4 Calicheamicin Conjugates Effectively Target Triple-Negative Breast and Ovarian Tumor-Initiating Cells to Result in Sustained Tumor Regressions. Clin Cancer Res. 2015 Sep 15;21(18):4165-73
[2]. de Vries JF, et al. The novel calicheamicin-conjugated CD22 antibody inotuzumab ozogamicin (CMC-544) effectively kills primary pediatric acute lymphoblastic leukemia cells. Leukemia. 2012 Feb;26(2):255-64
[3]. Takeshita A, et al. CMC-544 (inotuzumab ozogamicin), an anti-CD22 immuno-conjugate of calicheamicin, alters the levels of target molecules of malignant B-cells. Leukemia. 2009 Jul;23(7):1329-36.
Cell experiment: | The enhancement of the CDC effect is studied in a similar way in the presence of CMC-544 or G5/44. Specifically, after cells are incubated with or without CMC-544 (5 ng/mL calichemicin DMH) or G5/44 at 37°C for 2 h, they are washed 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 rituximab-free medium at 37°C for 0-48 h, CDC is analyzed. |
Animal experiment: | Cohorts of tumor-bearing mice (140-180 mm3) are randomized into study groups of 6 to 10 based on the number of available mice. The IDBS electronic notebook statistical package, Biobook, is used for automated animal randomization. Animals are dosed by intraperitoneal injection (or intravenously for 144580) twice a week for 4 cycles with ADC, or once a week for 2 cycles with 1.5 mg/kg doxorubicin for breast PDX tumors or 5 mg/kg Cisplatin for ovarian 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 (TTP) is determined to be the number of days between the first dose and the time at which mean tumor volume significantly increase (regrow) after regression. |
References: [1]. Damelin M, et al. Anti-EFNA4 Calicheamicin Conjugates Effectively Target Triple-Negative Breast and Ovarian Tumor-Initiating Cells to Result in Sustained Tumor Regressions. Clin Cancer Res. 2015 Sep 15;21(18):4165-73 | |
| Cas No. | 108212-75-5 | SDF | |
| Canonical SMILES | O[C@](CC1=O)(C#C/C=C\C#C2)/C(C([C@H]2O[C@@](O[C@H](C)[C@@H](NO[C@H](O[C@H](C)[C@H]3SC(C(C(C)=C(I)C(O[C@H](O[C@@H](C)[C@H](O)[C@H]4OC)[C@@H]4O)=C5OC)=C5OC)=O)C[C@@H]3O)[C@@H]6O)([H])[C@@H]6O[C@@](OC[C@@H]7NCC)([H])C[C@@H]7OC)=C1NC(OC)=O)=C\CSSSC | ||
| Formula | C55H74IN3O21S4 | M.Wt | 1368.35 |
| Solubility | DMSO : ≥ 100 mg/mL (73.08 mM);Water : < 0.1 mg/mL (insoluble) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 0.7308 mL | 3.654 mL | 7.3081 mL |
| 5 mM | 0.1462 mL | 0.7308 mL | 1.4616 mL |
| 10 mM | 0.0731 mL | 0.3654 mL | 0.7308 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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μL
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Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 24 reference(s) in Google Scholar.)
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