{"id":322,"date":"2022-01-06T11:00:03","date_gmt":"2022-01-06T11:00:03","guid":{"rendered":"http:\/\/c-ciarn.ca\/?p=322"},"modified":"2022-01-06T11:00:03","modified_gmt":"2022-01-06T11:00:03","slug":"%ef%bb%bfpgrmc1-has-been-reported-to-interact-with-multiple-proteins-including-insig-1-scap-p450-proteins-pair-bp1-and-epidermal-growth-factor-egfr29c33","status":"publish","type":"post","link":"https:\/\/c-ciarn.ca\/?p=322","title":{"rendered":"\ufeffPGRMC1 has been reported to interact with multiple proteins including Insig-1, SCAP, P450 proteins, PAIR-BP1, and epidermal growth factor (EGFR)[29C33]"},"content":{"rendered":"<p>\ufeffPGRMC1 has been reported to interact with multiple proteins including Insig-1, SCAP, P450 proteins, PAIR-BP1, and epidermal growth factor (EGFR)[29C33]. of siramesine, a generally accepted <a href=\"https:\/\/www.adooq.com\/mmv008138.html\">MMV008138<\/a> sigma-2 agonist, we have categorized our sigma-2 ligands into agonists, partial agonists, and antagonists. The establishment of functional assays for defining sigma-2 agonists and antagonists will facilitate functional characterization of sigma-2 receptor ligands and sigma-2 receptors. for sigma-1 receptors (nM)for sigma-2 receptors (nM) \/th th valign=&#8221;top&#8221; align=&#8221;right&#8221; rowspan=&#8221;1&#8243; colspan=&#8221;1&#8243; Recommendations \/th \/thead Azabicyclononane AnalogsSV1191417.05.2aSV1666292.028.3aWC-261436.02.6b2b262.05.9cYUN2452250.05.0cSV9592.53.1cBenzamide AnalogsRHM-13078.010.3dISO-1330.07.0eYUN2345484.012.4dYUN25212900.08.2dTropane AnalogRHM-138544.012.3fSiramesine Analogsiramesine17.00.12g Open in a separate windows a[14] b[34] c[35] d[16] e[36] fThe chemical structure of RHM-138 is usually published previously [24]. The binding affinities of RHM-138 for sigma-1 and sigma-2 affinities are not published previously. g[15] The determination of the potency of sigma-2 ligands to induce cell death in the cell viability assay and the caspase-3 assay The EC50 values of the sigma-2 ligands were decided in mouse breast cancer cell collection EMT-6 and human melanoma MMV008138 cell collection MDA-MB-435 using the cell viability assay. The data are shown in Table 2. The dose-response curves for the representative sigma-2 ligands (SV119, WC-26, RHM-1 and siramesine) are shown in Fig. 2A and C. Siramesine exhibited the most potent cytotoxicity with the EC50 values of 5.3 M and 9.3 M in EMT-6 and MDA-MB-435, respectively, after 48 hour treatment. The data are consistent with the EC50 values of siramesine in other cell lines reported previously [23, 27]. Open in a separate window Fig. 2 The dose response curves of the sigma-2 ligands in cell viability assay and caspase-3 activation assay. EMT-6 cells (A and B) or MDA-MB-435 cells (C and D) were treated with increasing concentrations of SV119 (), siramesine (), WC-26 (), or RHM-1 () for 24 h. The cell viability and caspase-3 activation were then determined by MTS assay (A and <a href=\"http:\/\/www.picnik.com\">LEPREL2 antibody<\/a> C) and caspase-3 assay (B and D), respectively. The bars represent mean SD in the representative experiment performed in triplicates. Table 2 MMV008138 EC50 of sigma-2 ligands in EMT-6 and MDA-MB-435 cell lines using MTS assay thead th valign=&#8221;top&#8221; align=&#8221;left&#8221; rowspan=&#8221;1&#8243; colspan=&#8221;1&#8243; \/th th colspan=&#8221;2&#8243; valign=&#8221;top&#8221; align=&#8221;center&#8221; rowspan=&#8221;1&#8243; EMT-6 \/th th colspan=&#8221;2&#8243; valign=&#8221;top&#8221; align=&#8221;center&#8221; rowspan=&#8221;1&#8243; MDA-MB-435 \/th th colspan=&#8221;5&#8243; valign=&#8221;bottom&#8221; align=&#8221;left&#8221; rowspan=&#8221;1&#8243; hr \/ \/th th valign=&#8221;top&#8221; align=&#8221;left&#8221; rowspan=&#8221;1&#8243; colspan=&#8221;1&#8243; Compound \/th th valign=&#8221;top&#8221; align=&#8221;right&#8221; rowspan=&#8221;1&#8243; colspan=&#8221;1&#8243; EC50 (M, 24h) \/th th valign=&#8221;top&#8221; align=&#8221;right&#8221; rowspan=&#8221;1&#8243; colspan=&#8221;1&#8243; EC50 (M, 48h) \/th th valign=&#8221;top&#8221; align=&#8221;right&#8221; rowspan=&#8221;1&#8243; colspan=&#8221;1&#8243; EC50 (M, 24h) \/th th valign=&#8221;top&#8221; align=&#8221;right&#8221; rowspan=&#8221;1&#8243; colspan=&#8221;1&#8243; EC50 (M, 48h) \/th \/thead Azabicyclononane AnalogsSV11916.0 1.411.4 1.736.7 3.318.5 1.9SV16630.0 1.018.5 2.134.1 4.425.0 5.57WC-2642.5 3.512.3 1.649.7 2.544.9 5.32b65.5 7.129 1.463.1 5.833.3 3.26YUN245 200154.5 30.4136.9 4.6101.0 15.1SV95 200 200 200 200Benzamide AnalogsRHM-1 200 200 200 200ISO-1 200 200 200 200YUN234 20091 12.7 200 200YUN252 200137.5 3.5 200 200Tropane AnalogSiramesine Analogsiramesine14.9 4.05.3 1.09.4 0.49.3 0.9 Open in a separate window Azabiocyclonane analogs exhibited different potency of cytotoxicity with EC50 values ranging from 11.4 M to 200 M. Benzamide analogs, YUN234, YUN252, MMV008138 RHM-1 and ISO-1, showed little cytotoxicity (Table 2 and Fig. 3). Tropane analog RHM-138 exhibited potent cytotoxicity. Open in a separate windows Fig. 3 Cytotoxicity of sigma-2 ligands using MTS assay. EMT-6 and MDA-MB-435 cells were treated with 50 M of sigma-2 ligands for 24h. MTS assay was then performed and cytotoxicity of the sigma-2 ligand was decided using the formula 1 and 2 explained in Material and Methods. The bars represent mean SD in three impartial experiments performed in triplicates. The EC50 values of the sigma-2 ligands were also decided using the caspase-3 assay in both EMT-6 and MDA-MB-435 cell lines. The data are shown in Table 3. The dose response curves for the.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>\ufeffPGRMC1 has been reported to interact with multiple proteins including Insig-1, SCAP, P450 proteins, PAIR-BP1, and epidermal growth factor (EGFR)[29C33]. of siramesine, a generally accepted MMV008138 sigma-2 agonist, we have categorized our sigma-2 ligands into agonists, partial agonists, and antagonists&#8230;.<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4],"tags":[],"class_list":["post-322","post","type-post","status-publish","format-standard","hentry","category-guanylyl-cyclase"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.5 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>\ufeffPGRMC1 has been reported to interact with multiple proteins including Insig-1, SCAP, P450 proteins, PAIR-BP1, and epidermal growth factor (EGFR)[29C33] - SGLT inhibitors in cancer therapy<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/c-ciarn.ca\/?p=322\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"\ufeffPGRMC1 has been reported to interact with multiple proteins including Insig-1, SCAP, P450 proteins, PAIR-BP1, and epidermal growth factor (EGFR)[29C33] - SGLT inhibitors in cancer therapy\" \/>\n<meta property=\"og:description\" content=\"\ufeffPGRMC1 has been reported to interact with multiple proteins including Insig-1, SCAP, P450 proteins, PAIR-BP1, and epidermal growth factor (EGFR)[29C33]. of siramesine, a generally accepted MMV008138 sigma-2 agonist, we have categorized our sigma-2 ligands into agonists, partial agonists, and antagonists....\" \/>\n<meta property=\"og:url\" content=\"https:\/\/c-ciarn.ca\/?p=322\" \/>\n<meta property=\"og:site_name\" content=\"SGLT inhibitors in cancer therapy\" \/>\n<meta property=\"article:published_time\" content=\"2022-01-06T11:00:03+00:00\" \/>\n<meta name=\"author\" content=\"webmaster\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"webmaster\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"3 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\\\/\\\/c-ciarn.ca\\\/?p=322#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/c-ciarn.ca\\\/?p=322\"},\"author\":{\"name\":\"webmaster\",\"@id\":\"https:\\\/\\\/c-ciarn.ca\\\/#\\\/schema\\\/person\\\/8b6dc5d86359d0c93ab67fe896511b29\"},\"headline\":\"\ufeffPGRMC1 has been reported to interact with multiple proteins including Insig-1, SCAP, P450 proteins, PAIR-BP1, and epidermal growth factor (EGFR)[29C33]\",\"datePublished\":\"2022-01-06T11:00:03+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/c-ciarn.ca\\\/?p=322\"},\"wordCount\":603,\"articleSection\":[\"Guanylyl Cyclase\"],\"inLanguage\":\"en-US\"},{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/c-ciarn.ca\\\/?p=322\",\"url\":\"https:\\\/\\\/c-ciarn.ca\\\/?p=322\",\"name\":\"\ufeffPGRMC1 has been reported to interact with multiple proteins including Insig-1, SCAP, P450 proteins, PAIR-BP1, and epidermal growth factor (EGFR)[29C33] - SGLT inhibitors in cancer therapy\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/c-ciarn.ca\\\/#website\"},\"datePublished\":\"2022-01-06T11:00:03+00:00\",\"author\":{\"@id\":\"https:\\\/\\\/c-ciarn.ca\\\/#\\\/schema\\\/person\\\/8b6dc5d86359d0c93ab67fe896511b29\"},\"breadcrumb\":{\"@id\":\"https:\\\/\\\/c-ciarn.ca\\\/?p=322#breadcrumb\"},\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\\\/\\\/c-ciarn.ca\\\/?p=322\"]}]},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\\\/\\\/c-ciarn.ca\\\/?p=322#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https:\\\/\\\/c-ciarn.ca\\\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"\ufeffPGRMC1 has been reported to interact with multiple proteins including Insig-1, SCAP, P450 proteins, PAIR-BP1, and epidermal growth factor (EGFR)[29C33]\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\\\/\\\/c-ciarn.ca\\\/#website\",\"url\":\"https:\\\/\\\/c-ciarn.ca\\\/\",\"name\":\"SGLT inhibitors in cancer therapy\",\"description\":\"Just another WordPress site\",\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\\\/\\\/c-ciarn.ca\\\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"en-US\"},{\"@type\":\"Person\",\"@id\":\"https:\\\/\\\/c-ciarn.ca\\\/#\\\/schema\\\/person\\\/8b6dc5d86359d0c93ab67fe896511b29\",\"name\":\"webmaster\",\"image\":{\"@type\":\"ImageObject\",\"inLanguage\":\"en-US\",\"@id\":\"https:\\\/\\\/secure.gravatar.com\\\/avatar\\\/eb1cb4edef28458891be40d78fdfb788d3338b4756f4d8e49eb1f0a5dc22bd8b?s=96&d=mm&r=g\",\"url\":\"https:\\\/\\\/secure.gravatar.com\\\/avatar\\\/eb1cb4edef28458891be40d78fdfb788d3338b4756f4d8e49eb1f0a5dc22bd8b?s=96&d=mm&r=g\",\"contentUrl\":\"https:\\\/\\\/secure.gravatar.com\\\/avatar\\\/eb1cb4edef28458891be40d78fdfb788d3338b4756f4d8e49eb1f0a5dc22bd8b?s=96&d=mm&r=g\",\"caption\":\"webmaster\"},\"sameAs\":[\"http:\\\/\\\/c-ciarn.ca\"],\"url\":\"https:\\\/\\\/c-ciarn.ca\\\/?author=1\"}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"\ufeffPGRMC1 has been reported to interact with multiple proteins including Insig-1, SCAP, P450 proteins, PAIR-BP1, and epidermal growth factor (EGFR)[29C33] - SGLT inhibitors in cancer therapy","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/c-ciarn.ca\/?p=322","og_locale":"en_US","og_type":"article","og_title":"\ufeffPGRMC1 has been reported to interact with multiple proteins including Insig-1, SCAP, P450 proteins, PAIR-BP1, and epidermal growth factor (EGFR)[29C33] - SGLT inhibitors in cancer therapy","og_description":"\ufeffPGRMC1 has been reported to interact with multiple proteins including Insig-1, SCAP, P450 proteins, PAIR-BP1, and epidermal growth factor (EGFR)[29C33]. of siramesine, a generally accepted MMV008138 sigma-2 agonist, we have categorized our sigma-2 ligands into agonists, partial agonists, and antagonists....","og_url":"https:\/\/c-ciarn.ca\/?p=322","og_site_name":"SGLT inhibitors in cancer therapy","article_published_time":"2022-01-06T11:00:03+00:00","author":"webmaster","twitter_card":"summary_large_image","twitter_misc":{"Written by":"webmaster","Est. reading time":"3 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"Article","@id":"https:\/\/c-ciarn.ca\/?p=322#article","isPartOf":{"@id":"https:\/\/c-ciarn.ca\/?p=322"},"author":{"name":"webmaster","@id":"https:\/\/c-ciarn.ca\/#\/schema\/person\/8b6dc5d86359d0c93ab67fe896511b29"},"headline":"\ufeffPGRMC1 has been reported to interact with multiple proteins including Insig-1, SCAP, P450 proteins, PAIR-BP1, and epidermal growth factor (EGFR)[29C33]","datePublished":"2022-01-06T11:00:03+00:00","mainEntityOfPage":{"@id":"https:\/\/c-ciarn.ca\/?p=322"},"wordCount":603,"articleSection":["Guanylyl Cyclase"],"inLanguage":"en-US"},{"@type":"WebPage","@id":"https:\/\/c-ciarn.ca\/?p=322","url":"https:\/\/c-ciarn.ca\/?p=322","name":"\ufeffPGRMC1 has been reported to interact with multiple proteins including Insig-1, SCAP, P450 proteins, PAIR-BP1, and epidermal growth factor (EGFR)[29C33] - SGLT inhibitors in cancer therapy","isPartOf":{"@id":"https:\/\/c-ciarn.ca\/#website"},"datePublished":"2022-01-06T11:00:03+00:00","author":{"@id":"https:\/\/c-ciarn.ca\/#\/schema\/person\/8b6dc5d86359d0c93ab67fe896511b29"},"breadcrumb":{"@id":"https:\/\/c-ciarn.ca\/?p=322#breadcrumb"},"inLanguage":"en-US","potentialAction":[{"@type":"ReadAction","target":["https:\/\/c-ciarn.ca\/?p=322"]}]},{"@type":"BreadcrumbList","@id":"https:\/\/c-ciarn.ca\/?p=322#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https:\/\/c-ciarn.ca\/"},{"@type":"ListItem","position":2,"name":"\ufeffPGRMC1 has been reported to interact with multiple proteins including Insig-1, SCAP, P450 proteins, PAIR-BP1, and epidermal growth factor (EGFR)[29C33]"}]},{"@type":"WebSite","@id":"https:\/\/c-ciarn.ca\/#website","url":"https:\/\/c-ciarn.ca\/","name":"SGLT inhibitors in cancer therapy","description":"Just another WordPress site","potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/c-ciarn.ca\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"en-US"},{"@type":"Person","@id":"https:\/\/c-ciarn.ca\/#\/schema\/person\/8b6dc5d86359d0c93ab67fe896511b29","name":"webmaster","image":{"@type":"ImageObject","inLanguage":"en-US","@id":"https:\/\/secure.gravatar.com\/avatar\/eb1cb4edef28458891be40d78fdfb788d3338b4756f4d8e49eb1f0a5dc22bd8b?s=96&d=mm&r=g","url":"https:\/\/secure.gravatar.com\/avatar\/eb1cb4edef28458891be40d78fdfb788d3338b4756f4d8e49eb1f0a5dc22bd8b?s=96&d=mm&r=g","contentUrl":"https:\/\/secure.gravatar.com\/avatar\/eb1cb4edef28458891be40d78fdfb788d3338b4756f4d8e49eb1f0a5dc22bd8b?s=96&d=mm&r=g","caption":"webmaster"},"sameAs":["http:\/\/c-ciarn.ca"],"url":"https:\/\/c-ciarn.ca\/?author=1"}]}},"_links":{"self":[{"href":"https:\/\/c-ciarn.ca\/index.php?rest_route=\/wp\/v2\/posts\/322","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/c-ciarn.ca\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/c-ciarn.ca\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/c-ciarn.ca\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/c-ciarn.ca\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=322"}],"version-history":[{"count":1,"href":"https:\/\/c-ciarn.ca\/index.php?rest_route=\/wp\/v2\/posts\/322\/revisions"}],"predecessor-version":[{"id":323,"href":"https:\/\/c-ciarn.ca\/index.php?rest_route=\/wp\/v2\/posts\/322\/revisions\/323"}],"wp:attachment":[{"href":"https:\/\/c-ciarn.ca\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=322"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/c-ciarn.ca\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=322"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/c-ciarn.ca\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=322"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}