Chetomin, an active component of Chaetomium globosum, is a heat shock protein 90/hypoxia-inducible factor 1 alpha (Hsp90/HIF1α) pathway inhibitor. Chetomin is a potent, nontoxic non-small cell lung cancer cancer stem cells (NSCLC CSC)-targeting molecule.
体外研究
Chetomin (0~10 μM; 24 hours; H460 and H1299 cells) shows progressively lower expression of several survival-promoting proteins promoted by Hsp90/HIF1α activity, including insulin-like growth factor 1 (IGF1 R), epidermal growth factor receptor (EGFR), Src, mitogen-activated protein kinase kinase 1/2 (MEK1/2), activation of protein kinase B (Akt), and mammalian target of rapamycin (mTOR) .
Chetomin (0~10 μM; 24 hours; H1299 cells) elicits cell cycle arrest in susceptible and chemoresistant NSCLC cell lines. .
Chetomin (1 µM; 3 days; H460 and H1299 cells) pretreatment abolishes their sphere-forming capacity. Chetomin inhibits sphere-forming by NSCLC CSCs within a nanomolar range, and proliferation of susceptible and chemoresistant NSCLC non-CSCs within a micromolar range. Chetomin (24 h) decreases HIF-response element activity in H460 and H1299 monolayer cultures. Chetomin (0~10 μM) specifically inhibits the Hsp90-HIF1α binding interaction in HIF1α's N-terminus .
Western Blot Analysis
Cell Line:
H460 and H1299 cells
Concentration:
0~10 μM
Incubation Time:
24 hours
Result:
Showed progressively lower expression of several survival-promoting proteins promoted by Hsp90/HIF1α activity, including insulin-like growth factor 1 (IGF1 R), epidermal growth factor receptor (EGFR), Src, mitogen-activated protein kinase kinase 1/2 (MEK1/2), activation of protein kinase B (Akt), and mammalian target of rapamycin (mTOR).
Cell Cycle Analysis
Cell Line:
H1299 cells
Concentration:
0~10 μM
Incubation Time:
24 hours
Result:
Elicited cell cycle arrest in susceptible and chemoresistant NSCLC cell lines.
体内研究
Chetomin (0~100 mg/kg; p.o.) inhibits lung tumorigenesis in NSCLC mouse models. .
Chetomin markedly decreases tumor formation in several murine models of NSCLC.
Animal Model:
Mouse
Dosage:
0~100 mg/kg
Administration:
P.o.
Result:
Inhibited lung tumorigenesis in NSCLC mouse models.
分子式
C31H30N6O6S4
分子量
710.87
CAS号
1403-36-7
运输条件
Room temperature in continental US; may vary elsewhere.