72263-05-9

中文名称 CONGLOBATIN

英文名称 CONGLOBATIN

CAS 72263-05-9

分子式 C28H38N2O6

分子量 498.61

MOL 文件 72263-05-9.mol

72263-05-9 结构式

基本信息物理化学性质安全数据常见问题列表

基本信息

中文别名

成球菌素

英文别名

FW-04-806
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 Germany3

海关编码29419000

常见问题列表

生物活性

Conglobatin (FW-04-806) 是一种从 Streptomyces conglobatus 培养物中分离得到的大环内酯双内酯。Conglobatin 是一种具有口服活性的 Hsp90 抑制剂，可以与 Hsp90 的 N 末端域结合，并破坏 Hsp90-Cdc37 复合物的形成。Conglobatin 可诱导人乳腺癌细胞和食道鳞状细胞癌细胞凋亡，并在体内表现出抗肿瘤活性。

靶点

HSP90

体外研究

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.

体内研究

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.