Irosustat (667-Coumate) is a potent steroid sulfatase inhibitor, with an IC50 of 8 nM, and exhibits anti-breast cancer activity.

Steroid sulfatase:IC50:8 nM, Steroid sulfatase (MCF-7 cells):0.2 nM

Irosustat (667 COUMATE), a potent steroid sulfatase inhibitor, exhibits an IC50 of 8 nM and inhibits steroid sulfatase (STS) activity in MCF-7 cells with an IC50 of 0.2 nM, without affecting the morphology or proliferation of MCF-7 cells at 10 μM.

Irosustat effectively inhibits over 90% of rat liver activity at a concentration of 1 mg/kg. At doses of 2 mg/kg administered orally for five days, it impedes uterine growth induced by oestrone sulfate (E1S) in ovariectomized rats. Additionally, when combined with E1S, Irosustat, at dosages of 2 and 10 mg/kg administered orally, reduces the growth of NMU-induced mammary tumors in these rats in a dose-dependent manner. Moreover, at a dosage of 10 mg/kg administered orally, Irosustat (identified as 667 COUMATE) achieves a 97.9 ± 0.06% inhibition of steroid sulphatase (STS) activity in rat liver.

MCF-7 cells are cultured in growth medium (minimum essential medium (MEM) containing, phenol red, 10% foetal calf serum (FCS) and essential nutrients). When the cells reach 60% confluency, they are treated with Irosustat (0.001-10 μM) in growth medium. After 72 h of incubation, photographs are taken under normal conditions of light and the number of attached cells in each flask is determined using a Coulter cell counter

Irosustat is formulated in propylene glycol.RatsLudwig rats bearing mammary tumors are used in the assay. Tumor development is monitored, and animals are ovariectomized when tumors reach 0.8-1.5 cm in diameter. Tumors are allowed to regress over a 12- to 13-day period to confirm their hormone-dependent status. Regrowth of tumors is stimulated with oestrone sulfate (E1S; 50 μg/day, s.c.). When tumors have regrown, animals continue to receive either E1S alone or E1S plus Irosustat at 10 mg/kg/day or 2 mg/kg/day, p.o., until tumor regression has occurred. Tumor volumes are calculated from two measured diameters.