species used for drug testing reveal different inhibition susceptibility for 17beta-hydroxysteroid dehydrogenase type 1物种用于药物测试揭示不同抑制易感性17 beta-hydroxysteroid脱氢酶1型.pdfVIP

Species Used for Drug Testing Reveal Different Inhibition Susceptibility for 17beta-Hydroxysteroid Dehydrogenase Type 1 ¨ 1 2¤a 1 ¨ 3 4 Gabriele Moller , Bettina Husen , Dorota Kowalik , Leena Hirvela , Dariusz Plewczynski , Leszek 5 2 2 1,6 ¤b Rychlewski , Josef Messinger , Hubert Thole , Jerzy Adamski * ¨ 1 Helmholtz Zentrum Munchen, Institute of Experimental Genetics, Genome Analysis Center, Neuherberg, Germany, 2 Solvay Pharmaceuticals Research Laboratories, Hannover, Germany, 3 Hormos Medical, Turku, Finland, 4 Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University, Warsaw, Poland, ´ ¨ ¨ ¨ 5 Bioinfobank Institute, Poznan, Poland, 6 Lehrstuhl fur Experimentelle Genetik, Technische Universitat Munchen, Freising-Weihenstephan, Germany Abstract Steroid-related cancers can be treated by inhibitors of steroid metabolism. In searching for new inhibitors of human 17beta- hydroxysteroid dehydrogenase type 1 (17b-HSD 1) for the treatment of breast cancer or endometriosis, novel substances based on 15-substituted estrone were validated. We checked the specificity for different 17b-HSD types and species. Compounds were tested for specificity in vitro not only towards recombinant human 17b-HSD types 1, 2, 4, 5 and 7 but also against 17b-HSD 1 of several other species including marmoset, pig, mouse, and rat. The latter are used in the processes of pharmacophore screening. We present the quantification of