108212-75-5
108212-75-5 structure
- Name: Calicheamicin
- Chemical Name: calicheamicin γ1I
- CAS Number: 108212-75-5
- Molecular Formula: C55H74IN3O21S4
- Molecular Weight: 1368.348
- Catalog: Signaling Pathways Antibody-drug Conjugate ADC Cytotoxin
- Create Date: 2018-09-28 22:07:22
- Modify Date: 2024-01-05 18:02:56
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Calicheamicin is a cytotoxic agent that causes double-strand DNA breaks.
| Name | calicheamicin γ1I |
|---|---|
| Synonyms |
.calicheamicin γ1
CLM-g1I S-[(2R,3S,4S,6S)-6-({[(2R,3S,4S,5R,6R)-5-{[(2S,4S,5S)-5-(Ethylamino)-4-methoxytetrahydro-2H-pyran-2-yl]oxy}-4-hydroxy-6-{[(2S,5Z,9R,13E)-9-hydroxy-12-[(methoxycarbonyl)amino]-13-[2-(methyltrisulfanyl)ethylidene]-11-oxobicyclo[7.3.1]trideca-1(12),5-diene-3,7-diyn-2-yl]oxy}-2-methyltetrahydro-2H-pyran-3-yl]amino}oxy)-4-hydroxy-2-methyltetrahydro-2H-pyran-3-yl] 4-{[(2S,3R,4R,5S,6S)-3,5-dihydroxy-4-methoxy-6-methyltetrahydro-2H-pyran-2-yl]oxy}- Calicheamicin g1I calicheamicin γ1 I Calichemicin g1 .calichaemicin γ1 calicheamicin gamma1(I) Calicheamicin γ1I Calicheamicin Gamma1 Calichemicin γ1 CALICHEAMICIN GAMMA(1)I |
| Description | Calicheamicin is a cytotoxic agent that causes double-strand DNA breaks. |
|---|---|
| Related Catalog | |
| In Vitro | 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]. |
| In Vivo | 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]. |
| Cell Assay | 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 Admin | 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 |
| Density | 1.6±0.1 g/cm3 |
|---|---|
| Molecular Formula | C55H74IN3O21S4 |
| Molecular Weight | 1368.348 |
| Exact Mass | 1367.274170 |
| PSA | 409.64000 |
| LogP | 11.89 |
| Index of Refraction | 1.662 |
| Storage condition | 2-8℃ |
|
~90%
108212-75-5 |
| Literature: Journal of the American Chemical Society, , vol. 114, # 25 p. 10082 - 10084 |
|
~%
108212-75-5 |
| Literature: Angewandte Chemie, , vol. 106, # 8 p. 928 - 931 |
| Precursor 2 | |
|---|---|
| DownStream 5 | |
![S-[(2R,3S,4S,6S)-6-({[(2R,3S,4S,5R,6S)-5-{[(2S,4S,5S)-5-(Ethylamino)-4-methoxytetrahydro-2H-pyran-2-yl]oxy}-4-hydroxy-6-({(9R,14S)-9-hydroxy-14-[(methoxycarbonyl)amino]-15-oxo-13-thiatetracyclo[7.4.3.01,10.03,8]hexadeca-3,5,7,10-tetraen-2-yl}oxy)-2-methyltetrahydro-2H-pyran-3-yl]amino}oxy)-4-hydroxy-2-methyltetrahydro-2H-pyran-3-yl] 4-{[(3R,4R,5S,6S)-3,5-dihydroxy-4-methoxy-6-methyltetrahydro-2H-pyran-2-yl]oxy}-3-iodo-5,6-dimethoxy-2-me structure](https://www.chemsrc.com/caspic/015/122470-58-0.png)
