{"id":17809,"date":"2026-08-24T09:44:44","date_gmt":"2026-08-24T09:44:44","guid":{"rendered":"https:\/\/www.sygnaturediscovery.com\/?post_type=journal-paper&#038;p=17809"},"modified":"2026-08-24T09:45:36","modified_gmt":"2026-08-24T09:45:36","slug":"beyond-cytotoxic-payloads-for-antibody-drug-conjugates-a-medicinal-chemistry-perspective","status":"publish","type":"journal-paper","link":"https:\/\/www.sygnaturediscovery.com\/fr\/journal-paper\/beyond-cytotoxic-payloads-for-antibody-drug-conjugates-a-medicinal-chemistry-perspective\/","title":{"rendered":"Beyond Cytotoxic Payloads for Antibody Drug Conjugates &#8211; A Medicinal Chemistry Perspective"},"content":{"rendered":"\n<p class=\"wp-block-paragraph\"><strong>Allan Jordan, Stuart Best, and Joshua Greally<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Abstract<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Despite significant research and investment, antibody\u2212drug conjugates (ADCs) primarily rely on a limited number of broadly cytotoxic payloads that contribute significantly to toxicity. More recently, there has been a migration toward mechanistically targeted payloads, pairing improved antibodies with small molecules that act on disease-specific biology, improving precision and tolerability. Designing these next-generation payloads means rethinking some of our design metrics and guidelines derived from traditional medicinal chemistry: properties such as LogD, pKa, permeability, efflux, and metabolic stability must be carefully balanced to ensure efficient intracellular release while limiting systemic exposure. Here we discuss our observations around these properties and suggest design rules and guidelines for the optimization of next-generation ADC payloads.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Ref: <a href=\"https:\/\/doi.org\/10.1021\/acs.bioconjchem.6c00322\" data-type=\"link\" data-id=\"https:\/\/doi.org\/10.1021\/acs.bioconjchem.6c00322\">Bioconjugate Chemistry 2026<\/a><\/p>\n\n\n\n<p class=\"has-text-2-xl-font-size wp-block-paragraph\"><strong>Interested in reading our publication but don&rsquo;t have a subscription to ACS Bioconjugate Chemistry? <\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Contact us to request a PDF copy. We have 50 complimentary copies available for eligible researchers and professionals.<\/p>\n\n\n\n<div class=\"wp-block-buttons is-layout-flex wp-block-buttons-is-layout-flex\">\n<div class=\"wp-block-button\" modaltype=\"\"><a class=\"wp-block-button__link wp-element-button\" href=\"mailto:marketing@sygnaturediscovery.com\">Submit Your Request<\/a><\/div>\n<\/div>\n\n\n\n<p class=\"wp-block-paragraph\"><\/p>\n","protected":false},"excerpt":{"rendered":"","protected":false},"featured_media":0,"template":"","category":[],"resource_tag":[],"class_list":["post-17809","journal-paper","type-journal-paper","status-publish","hentry"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.0 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Beyond Cytotoxic Payloads for Antibody Drug Conjugates - A Medicinal Chemistry Perspective - Sygnature<\/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:\/\/www.sygnaturediscovery.com\/fr\/journal-paper\/beyond-cytotoxic-payloads-for-antibody-drug-conjugates-a-medicinal-chemistry-perspective\/\" \/>\n<meta property=\"og:locale\" content=\"fr_CA\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Beyond Cytotoxic Payloads for Antibody Drug Conjugates - A Medicinal Chemistry Perspective - Sygnature\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.sygnaturediscovery.com\/fr\/journal-paper\/beyond-cytotoxic-payloads-for-antibody-drug-conjugates-a-medicinal-chemistry-perspective\/\" \/>\n<meta property=\"og:site_name\" content=\"Sygnature\" \/>\n<meta property=\"article:modified_time\" content=\"2026-08-24T09:45:36+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/02\/sygnature-hit-to-lead-team-collaboration-scaled.webp\" \/>\n\t<meta property=\"og:image:width\" content=\"2560\" \/>\n\t<meta property=\"og:image:height\" content=\"1707\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/webp\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Estimation du temps de lecture\" \/>\n\t<meta name=\"twitter:data1\" content=\"1 minute\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/journal-paper\\\/beyond-cytotoxic-payloads-for-antibody-drug-conjugates-a-medicinal-chemistry-perspective\\\/\",\"url\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/journal-paper\\\/beyond-cytotoxic-payloads-for-antibody-drug-conjugates-a-medicinal-chemistry-perspective\\\/\",\"name\":\"Beyond Cytotoxic Payloads for Antibody Drug Conjugates - A Medicinal Chemistry Perspective - Sygnature\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/#website\"},\"datePublished\":\"2026-08-24T09:44:44+00:00\",\"dateModified\":\"2026-08-24T09:45:36+00:00\",\"breadcrumb\":{\"@id\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/journal-paper\\\/beyond-cytotoxic-payloads-for-antibody-drug-conjugates-a-medicinal-chemistry-perspective\\\/#breadcrumb\"},\"inLanguage\":\"fr-CA\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/journal-paper\\\/beyond-cytotoxic-payloads-for-antibody-drug-conjugates-a-medicinal-chemistry-perspective\\\/\"]}]},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/journal-paper\\\/beyond-cytotoxic-payloads-for-antibody-drug-conjugates-a-medicinal-chemistry-perspective\\\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/page-daccueil\\\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Beyond Cytotoxic Payloads for Antibody Drug Conjugates &#8211; 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