We have compared the antitumor activities of
SP500263, a novel next-generation
selective estrogen receptor modulator (
SERM),
tamoxifen, and
raloxifene side-by-side in in vitro and in vivo MCF-7
breast cancer models. In vitro,
SP500263 acted as an
antiestrogen and potently inhibited
estrogen-dependent MCF-7 proliferation with IC(50) values in the nanomolar range.
SP500263 also strongly inhibited MCF-7 proliferation in the absence of
estrogen at all of the concentrations tested. To investigate the antitumor activity of
SP500263 in animals, athymic nude mice were implanted with MCF-7
tumor in the presence of a
tumor growth-supporting sustained release
estrogen pellet. Treatment was initiated after
tumors were established.
SP500263, administered for 28 days through daily i.p. dosing, effectively reduced
estrogen-stimulated
tumor growth at 3 and 30 mg/kg.
SP500263 was as efficacious as
tamoxifen and superior to
raloxifene at the corresponding doses. Maximum efficacy was reached with the 30 mg/kg dose. The observed effects were highly significant.
SP500263 represents a member of a novel series of
SERMs that is structurally unrelated to
SERMs currently on the market or in clinical development. The experiments described herein demonstrate that
SP500263 is efficacious in the MCF-7 proliferation assay and in a murine model of
breast cancer.