8053-00-7Relevant articles and documents
Diethylstilbestrol-scaffold-based pregnane X receptor modulators
Hodnik, ?iga,Toma?i?, Tihomir,Smodi?, Domen,D'Amore, Claudio,Ma?i?, Lucija Peterlin,Fiorucci, Stefano,Kikelj, Danijel
, p. 551 - 562 (2015/10/12)
Due to its function as a regulator of drug-metabolizing enzymes and transporters, pregnane X receptor (PXR) represents an important factor involved in drug metabolism. In this work, we describe the discovery of diethylstilbestrol-based PXR modulators, which were designed from marine sulfated steroids with PXR agonistic activity, solomonsterols A and B, and our recently reported bazedoxifene scaffold-derived PXR antagonists. The methylated diethylstilbestrol derivative 1 displayed potent PXR agonistic activity with an EC50 value of 10.5 μM, whereas compounds 3, 4 and 6 (IC50 for 6 = 27.4 μM) and diethylstilbestrol (2) itself (IC50 = 14.6 μM) exhibited PXR antagonistic effects in HepG2 cells. The PXR modulatory effects of the synthesized diethylstilbestrol derivatives were further confirmed by the induction of PXR-regulated CYP3A4 expression with compound 1, as well as by the inhibition of the rifaximin-promoted up-regulation of CYP3A4 expression with 2 and its derivative 6.
THERAPEUTIC FOR HEPATIC CANCER
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, (2011/02/18)
A novel pharmaceutical composition for treating or preventing hepatocellular carcinoma and a method of treatment are provided. A pharmaceutical composition for treating or preventing liver cancer is obtained by combining a chemotherapeutic agent with an anti-glypican 3 antibody. Also disclosed is a pharmaceutical composition for treating or preventing liver cancer which comprises as an active ingredient an anti-glypican 3 antibody for use in combination with a chemotherapeutic agent, or which comprises as an active ingredient a chemotherapeutic agent for use in combination with an anti-glypican 3 antibody. Using the chemotherapeutic agent and the anti-glypican 3 antibody in combination yields better therapeutic effects than using the chemotherapeutic agent alone, and mitigates side effects that arise from liver cancer treatment with the chemotherapeutic agent.
Synthesis and biological evaluation of stilbene-based pure estrogen antagonists
Walter, Georg,Liebl, Renate,Von Angerer, Erwin
, p. 4659 - 4663 (2007/10/03)
The nonsteroidal estrogen diethylstilbestrol can be converted into potent antiestrogens devoid of agonist activity by introduction of side chains with appropriate functional groups. Replacement of one of the ethyl substituents in diethylstilbestrol by side chains with functional groups converted this potent estrogen into pure antiestrogens with the potential for the treatment of breast cancer. These agents completely suppressed estrogen receptor-mediated gene activation and inhibited the growth of estrogen-sensitive MCF-7 breast cancer cells in submicromolar concentrations. The most potent derivative displayed similar activity as fulvestrant (ICI 182,780) in vitro and in the mouse uterine weight test. Obviously, the stilbene structure can act as a substitute for estradiol in the development of pure estrogen antagonists.