[et_pb_section fb_built=”1″ admin_label=”Class Details Section” _builder_version=”3.23.3″ background_color=”#ffffff” custom_padding=”0px||0px|”][et_pb_row custom_padding=”||5px|||” _builder_version=”3.23.3″][et_pb_column type=”4_4″ _builder_version=”3.23.3″][et_pb_text _builder_version=”3.23.3″ custom_margin=”||15px|||”]<\/p>\n
[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row _builder_version=”3.23.3″][et_pb_column type=”4_4″ _builder_version=”3.23.3″][et_pb_tabs active_tab_background_color=”#109dc0″ inactive_tab_background_color=”#109dc0″ active_tab_text_color=”#ffffff” _builder_version=”3.23.3″ tab_text_color=”#ffffff” body_font=”||||||||” tab_font=”||||||||” tab_line_height=”1.8em”][et_pb_tab title=”\u00bb” _builder_version=”3.23.3″][\/et_pb_tab][et_pb_tab title=”ABSTRACT” _builder_version=”3.23.3″ body_font=”||||||||” tab_font=”||||||||”]Steroid sulfatase (STS) catalyzes the desulfation of biologically inactive sulfated steroids to yield biologically active desulfated steroids and is currently being examined as a target for therapeutic intervention for the treatment of breast cancer. We previously demonstrated that 4-formyl estrone is a time- and concentration-dependent inhibitor of STS. We have prepared a series of 4-formylated estrogens and examined them as irreversible STS inhibitors. Introducing a formyl, bromo or nitro group at the 2-position of 4-formylestrone resulted in loss of concentration and time-dependent inhibition and a considerable decrease in binding affinity. An estradiol derivative bearing a formyl group at the 4-position and a benzyl group at the 17\u03b2-position yielded a potent concentration and time-dependent STS inhibitor with a K(I) of 85 nM and a k(inact) of 0.021 min(-1) (k(inact)\/K(I) of 2.3 \u00d7 10(5)M(-1)min(-1)). Studies with estrone or estradiol substituted at the 4-position with groups other than a formyl group revealed that good reversible inhibitors can be obtained by introducing small electron withdrawing groups at this position. An estradiol derivative with fluorine at the 4-position and a benzyl group at the 17\u03b2-position yielded a potent, reversible inhibitor of STS with an IC(50) of 40 nM. The introduction of relatively small electron withdrawing groups at the 4-position of estrogens and their derivatives may prove to be a general approach to enhancing the potency of estrogen-derived STS inhibitors. [\/et_pb_tab][et_pb_tab title=”PDF” _builder_version=”3.23.3″ link_option_url=”https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0968089611006808?via%3Dihub” link_option_url_new_window=”on”]Download PDF »[\/et_pb_tab][et_pb_tab title=”SUPPORTING INFORMATION” _builder_version=”3.23.3″ link_option_url=”https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0968089611006808?via%3Dihub”]View on PubMed »[\/et_pb_tab][\/et_pb_tabs][\/et_pb_column][\/et_pb_row][et_pb_row _builder_version=”3.23.3″][et_pb_column type=”4_4″ _builder_version=”3.23.3″][et_pb_gallery gallery_ids=”2233″ fullwidth=”on” _builder_version=”3.23.3″][\/et_pb_gallery][\/et_pb_column][\/et_pb_row][et_pb_row _builder_version=”3.23.3″][et_pb_column type=”4_4″ _builder_version=”3.23.3″][et_pb_text _builder_version=”3.23.3″]<\/p>\n
Phan, C.-M.; Liu, Y.;\u00a0Kim, B.<\/u>; Mostafa, Y.; Taylor, S. D. Bioorg. Med. Chem.\u00a02011<\/b>, 19, 5999\u20136005.<\/p>\n
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3.\u00a0Inhibition of Steroid Sulfatase with 4-Substituted Estrone and Estradiol Derivatives Steroid sulfatase (STS) catalyzes the desulfation of biologically inactive sulfated steroids to yield biologically active desulfated steroids and is currently being examined as a target for therapeutic intervention for the treatment of breast cancer. We previously demonstrated that 4-formyl estrone is a time- and concentration-dependent […]<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"","_et_gb_content_width":"","footnotes":""},"categories":[13,12],"tags":[],"class_list":["post-2231","post","type-post","status-publish","format-standard","hentry","category-prior-to-clemson","category-synthesis"],"_links":{"self":[{"href":"https:\/\/scienceweb.clemson.edu\/kimgroup\/wp-json\/wp\/v2\/posts\/2231","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/scienceweb.clemson.edu\/kimgroup\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/scienceweb.clemson.edu\/kimgroup\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/scienceweb.clemson.edu\/kimgroup\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/scienceweb.clemson.edu\/kimgroup\/wp-json\/wp\/v2\/comments?post=2231"}],"version-history":[{"count":0,"href":"https:\/\/scienceweb.clemson.edu\/kimgroup\/wp-json\/wp\/v2\/posts\/2231\/revisions"}],"wp:attachment":[{"href":"https:\/\/scienceweb.clemson.edu\/kimgroup\/wp-json\/wp\/v2\/media?parent=2231"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/scienceweb.clemson.edu\/kimgroup\/wp-json\/wp\/v2\/categories?post=2231"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/scienceweb.clemson.edu\/kimgroup\/wp-json\/wp\/v2\/tags?post=2231"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}