Conglobatin

Conglobatin (FW-04-806), a macrolide dilactone, is isolated from the culture of Streptomyces conglobatus. Conglobatin is an orally active Hsp90 inhibitor. Conglobatin can bind to the N-terminal domain of Hsp90 and disrupt Hsp90-Cdc37 complex formation. Conglobatin induces apoptosis in human breast cancer cells and esophageal squamous cell carcinoma cells, and exhibits antitumor activity in vivo^[1][2][3]. IC50 & Target:Hsp90^[2]
Apoptosis^[2][3] In Vitro: Conglobatin (6.25-100 μM; 48 h) markedly inhibits the proliferation of SKBR3 and MCF-7 cells, with IC₅₀s of 12.11 and 39.44 μM, respectively^[2].
Conglobatin inhibits cell proliferation in EC109, KYSE70, KYSE450, KYSE150, KYSE180, and KYSE510 cells, with IC₅₀s of 16.43, 15.89, 10.94, 10.50, 10.28, and 9.31 μM, respectively^[3].
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^[2].
Conglobatin (10-40 μM; 3-24 h) reduces Hsp90 client protein levels and induces proteasome-dependent degradation^[2].
Conglobatin binds to the N-terminal of Hsp90, does not affect ATP-binding capability of Hsp90, but inhibits Hsp90/Cdc37 chaperone/co-chaperone interactions^[2]. In Vivo: 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^[2].
Conglobatin (4-8 mg/kg; i.p. daily for 21 days) inhibits tumor growth in EC109 and KYSE510 tumor xenograft models with low toxicity^[3]