72263-05-9
基本信息
CONGLOBATIN
Conglobatin, >=99%
(3E,5R,7S,8S,11E,13R,15S,16S)-3,5,7,11,13,15-Hexamethyl-8,16-bis(5-oxazolylmethyl)-1,9-dioxacyclohexadeca-3,11-diene-2,10-dione
1,9-Dioxacyclohexadeca-3,11-diene-2,10-dione, 3,5,7,11,13,15-hexamethyl-8,16-bis(5-oxazolylmethyl)-, (3E,5R,7S,8S,11E,13R,15S,16S)-
物理化学性质
| 密度 | 1.060±0.06 g/cm3 (20 ºC 760 Torr) |
| 储存条件 | -20°C |
| 溶解度 | DMF: soluble; DMSO: soluble; Ethanol: soluble; Methanol: soluble |
| 形态 | 白色至类白色固体 |
安全数据
| WGK Germany | 3 |
| 海关编码 | 29419000 |
常见问题列表
|
HSP90
|
Conglobatin (6.25-100 μM; 48 h) markedly inhibits the proliferation of SKBR3 and MCF-7 cells, with IC
50
s of 12.11 and 39.44 μM, respectively.
Conglobatin inhibits cell proliferation in EC109, KYSE70, KYSE450, KYSE150, KYSE180, and KYSE510 cells, with IC
50
s of 16.43, 15.89, 10.94, 10.50, 10.28, and 9.31 μM, respectively.
Conglobatin (10-40 μM; 24 h) displays obvious arrest of SKBR3 and MCF-7 cells in the G2/M phase. Conglobatin induces apoptosis through caspase-dependent pathways in SKBR3 and MCF-7 cells.
Conglobatin (10-40 μM; 3-24 h) reduces Hsp90 client protein levels and induces proteasome-dependent degradation.
Conglobatin binds to the N-terminal of Hsp90, does not affect ATP-binding capability of Hsp90, but inhibits Hsp90/Cdc37 chaperone/co-chaperone interactions.
Cell Proliferation Assay
| Cell Line: | SKBR3 and MCF-7 cells |
| Concentration: | 6.25, 12.5, 25, 50, 100 μM |
| Incubation Time: | 48 hours |
| Result: | Inhibited the proliferation of SKBR3 and MCF-7 cells in a dose-dependent manner. |
Cell Cycle Analysis
| Cell Line: | SKBR3 and MCF-7 cells |
| Concentration: | 10, 20, 40 μM |
| Incubation Time: | 24 hours |
| Result: | Increased the G2/M cell population and decreased the population in the S and G0/G1 phases. |
Western Blot Analysis
| Cell Line: | SKBR3 and MCF-7 cells |
| Concentration: | 10, 20, 40 μM |
| Incubation Time: | 3, 6, 12, 24 hours |
| Result: |
Decreased the levels of the client proteins HER2, p-HER2, Raf-1, Akt, and p-Akt in a dose and time-dependent manner in SKBR3 cells.
Reduced the the levels of the client proteins Raf-1, Akt, and p-Akt in a dose and time-dependent manner in MCF-7 cells. |
Conglobatin (50-200 mg/kg; i.g. q3d for 24 d) inhibits the tumor growth of SKBR3 and MCF-7 human breast cancer xenograft models in a dose-dependent manner.
Conglobatin (4-8 mg/kg; i.p. daily for 21 days) inhibits tumor growth in EC109 and KYSE510 tumor xenograft models with low toxicity
| Animal Model: | BALB/c (nu/nu) athymic mice with SKBR3 and MCF-7 tumor xenograft |
| Dosage: | 50, 100, 200 mg/kg |
| Administration: | Oral gavage every 3 days for 24 days |
| Result: |
Showed inhibition of tumor growth at a rate of 39.1%, 52.7%, and 67.5% in the SKBR3 cell line groups and 27.3%, 39.8%, 54.3% in the MCF-7 cell line groups at the three increasing doses, respectively.
Was well tolerated. |