{"id":56029,"date":"2023-04-20T01:03:32","date_gmt":"2023-04-19T23:03:32","guid":{"rendered":"https:\/\/pharma-trend.com\/en\/circle-pharmas-first-in-class-orally-bioavailable-macrocyclic-cyclin-a-b-inhibitors-highlighted-in-poster-presentations-at-american-association-for-cancer-research-annual-meeting\/"},"modified":"2023-04-20T01:03:32","modified_gmt":"2023-04-19T23:03:32","slug":"circle-pharmas-first-in-class-orally-bioavailable-macrocyclic-cyclin-a-b-inhibitors-highlighted-in-poster-presentations-at-american-association-for-cancer-research-annual-meeting","status":"publish","type":"post","link":"https:\/\/pharma-trend.com\/en\/circle-pharmas-first-in-class-orally-bioavailable-macrocyclic-cyclin-a-b-inhibitors-highlighted-in-poster-presentations-at-american-association-for-cancer-research-annual-meeting\/","title":{"rendered":"Circle Pharma\u2019s first-in-class orally bioavailable macrocyclic cyclin A\/B inhibitors highlighted in poster presentations at American Association for Cancer Research Annual Meeting"},"content":{"rendered":"<div>\n<ul class=\"bwlistdisc\">\n<li>\n<b>Data show activity across a wide range of human tumor cell lines<\/b><\/li>\n<li>\n<b>Tumor regression observed in xenograft models of small cell lung cancer and ovarian cancer<\/b><\/li>\n<li>\n<b>Research from the laboratory of Dr. Matthew Oser at the Dana Farber Cancer Institute identified the key role of the SAC complex in selective tumor cell killing by cyclin A\/B inhibitors<\/b><\/li>\n<\/ul>\n<p>SAN FRANCISCO&#8211;(BUSINESS WIRE)&#8211;Circle Pharma announced today that two poster presentations at the American Association for Cancer Research (AACR) Annual Meeting held April 14-19, in Orlando, Florida, highlight promising pre-clinical data of its first-in-class orally bioavailable macrocyclic cyclin A\/B inhibitors targeting intractable cancers. Circle expects to advance its cyclin A\/B inhibitor program into IND-enabling studies later this year and subsequently into clinical development for testing in a range of cancer types, including SCLC.<\/p>\n<p><a href=\"https:\/\/mms.businesswire.com\/media\/20230419006030\/en\/432777\/5\/logo-Circle-Pharma.jpg\"><img decoding=\"async\" src=\"https:\/\/mms.businesswire.com\/media\/20230419006030\/en\/432777\/21\/logo-Circle-Pharma.jpg\"><\/a><\/p>\n<p>\nThe data presented by Circle Pharma shows activity across a wide range of human tumor cell lines and tumor regression in xenograft models of small cell lung carcinoma (SCLC) and ovarian cancer. Pre-clinical development of orally bioavailable macrocycles with dual cyclin A and B inhibitory activity drive synthetic lethality in multiple tumor types. The compounds are shown to be well-tolerated in mice with no observed body weight loss, neutropenia, or depletion of bone marrow across all dose regimens. In vitro studies showed that target engagement in cells leads to displacement of E2F1 from Cyclin A:CDK2 and Myt1 from Cyclin B:CDK1, and the compounds induce DNA damage, G<sub>2<\/sub>\/M arrest, and apoptosis. The presentation further showed that sensitivity in SCLC cell lines is correlated with RB dysfunction and E2F1 target gene expression.<\/p>\n<p>\nIn addition, studies conducted by the laboratory of Matthew Oser at Dana Farber Cancer Institute (DFCI) validate that cyclin A\/B inhibitors induce mitotic arrest and apoptosis in SCLC cell lines. The researchers deployed a genome wide CRISPR\/Cas9 positive selection screen to identify that activation of the mitotic spindle assembly checkpoint (SAC) complex by the kinase MSP1 is a dominant mechanism for selective cancer cell killing by the cyclin A\/B inhibitors. Dr. Oser\u2019s laboratory at DFCI was sponsored by Circle Pharma.<\/p>\n<table cellspacing=\"0\" class=\"bwtablemarginb bwblockalignl\">\n<tr>\n<td class=\"bwvertalignt bwtopsingle bwsinglebottom bwleftsingle bwrightsingle bwpadl1\" colspan=\"1\" rowspan=\"1\">\n<p class=\"bwcellpmargin\">\n<b>Program<\/b><\/p>\n<\/td>\n<td class=\"bwvertalignt bwtopsingle bwsinglebottom bwrightsingle bwpadl1\" colspan=\"1\" rowspan=\"1\">\n<p class=\"bwcellpmargin\">\n<b>Presentation Details<\/b><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td class=\"bwvertalignt bwsinglebottom bwleftsingle bwrightsingle bwpadl1\" colspan=\"1\" rowspan=\"1\">\n<p class=\"bwcellpmargin\">\n<b>Cyclin A\/B<\/b><\/p>\n<\/td>\n<td class=\"bwvertalignt bwsinglebottom bwrightsingle bwpadl1\" colspan=\"1\" rowspan=\"1\">\n<p class=\"bwcellpmargin\">\n<b>Abstract Number: 1559<\/b><\/p>\n<p class=\"bwcellpmargin\">\n<b>Abstract Title: Mechanisms responsible for hypersensitivity of small cell lung cancers to novel cyclin A\/B RxL macrocyclic peptide inhibitors<\/b><\/p>\n<p class=\"bwcellpmargin\">\n<b>Session Title: Experimental and Molecular Therapeutics<\/b><\/p>\n<p class=\"bwcellpmargin\">\n<b>Session Type: Poster<\/b><\/p>\n<p class=\"bwcellpmargin\">\n\u00a0<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td class=\"bwvertalignt bwsinglebottom bwleftsingle bwrightsingle bwpadl1\" colspan=\"1\" rowspan=\"1\">\n<p class=\"bwcellpmargin\">\n<b>Cyclin A\/B<\/b><\/p>\n<\/td>\n<td class=\"bwvertalignt bwsinglebottom bwrightsingle bwpadl1\" colspan=\"1\" rowspan=\"1\">\n<p class=\"bwcellpmargin\">\n<b>Abstract Number: 1560<\/b><\/p>\n<p class=\"bwcellpmargin\">\n<b>Abstract Title: Orally bioavailable macrocycles that target cyclins A and B RxL motifs cause tumor regression in xenograft models and in vitro show activity across multiple cancer types<\/b><\/p>\n<p class=\"bwcellpmargin\">\n<b>Session Title: Experimental and Molecular Therapeutics<\/b><\/p>\n<p class=\"bwcellpmargin\">\n<b>Session Type: Poster<\/b><\/p>\n<\/td>\n<\/tr>\n<\/table>\n<p>\n<b>About Circle Pharma, Inc.<\/b><\/p>\n<p>\nCircle is a biopharmaceutical company advancing the discovery and development of intrinsically cell-permeable macrocycles that can be delivered by multiple routes, including oral administration. Circle\u2019s MXMO\u2122 platform combines structure-based rational drug design and advanced synthetic chemistry to develop first-in-class macrocycle therapeutics for challenging targets to address unmet clinical needs. Circle\u2019s macrocycle can address both intra- and extra-cellular therapeutic targets and is applicable across a wide range of serious diseases; the company is initially focusing its development efforts on intracellular protein-protein interactions that are key drivers in cancer but have remained elusive to other treatment modalities. Circle is headquartered in South San Francisco and has raised $160 million to date from leading life sciences investors including The Column Group, Nextech, Pfizer and Eli Lilly.<\/p>\n<p>\nTo learn more about Circle Pharma please visit <a target=\"_blank\" href=\"https:\/\/cts.businesswire.com\/ct\/CT?id=smartlink&amp;url=http%3A%2F%2Fwww.circlepharma.com&amp;esheet=53384456&amp;newsitemid=20230419006030&amp;lan=en-US&amp;anchor=www.circlepharma.com&amp;index=1&amp;md5=001fa2e9d6406f241860aa2e0c921ea5\" rel=\"nofollow noopener\" shape=\"rect\">www.circlepharma.com<\/a>.<\/p>\n<p> <b>Contacts<\/b> <\/p>\n<p>\nCircle Pharma Media Contact:<br \/>\n<br \/>Eleanor Lim<br \/>\n<br \/>650.825.4099<br \/>\n<br \/><a target=\"_blank\" href=\"&#109;&#x61;&#105;&#x6c;&#116;&#x6f;:&#x69;n&#102;&#x6f;&#64;&#x63;&#105;&#x72;c&#x6c;e&#112;&#x68;&#97;&#x72;&#109;&#x61;&#46;&#x63;o&#x6d;\" rel=\"nofollow noopener\" shape=\"rect\">&#x69;&#x6e;&#102;o&#64;&#x63;&#x69;&#114;&#99;l&#x65;&#x70;&#104;&#97;r&#x6d;&#x61;&#x2e;&#99;om<\/a><\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Data show activity across a wide range of human tumor cell lines Tumor regression observed in xenograft models of small cell lung cancer and ovarian cancer Research from the laboratory of Dr. Matthew Oser at the Dana Farber Cancer Institute identified the key role of the SAC complex in selective tumor cell killing by cyclin &#8230; <span class=\"more\"><a class=\"more-link\" href=\"https:\/\/pharma-trend.com\/en\/circle-pharmas-first-in-class-orally-bioavailable-macrocyclic-cyclin-a-b-inhibitors-highlighted-in-poster-presentations-at-american-association-for-cancer-research-annual-meeting\/\">[Read more&#8230;]<\/a><\/span><\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[13],"tags":[],"class_list":["entry","post","publish","author-business","post-56029","format-standard","category-industry"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.7 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Circle Pharma\u2019s first-in-class orally bioavailable macrocyclic cyclin A\/B inhibitors highlighted in poster presentations at American Association for Cancer Research Annual Meeting - Pharma Trend<\/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:\/\/pharma-trend.com\/en\/circle-pharmas-first-in-class-orally-bioavailable-macrocyclic-cyclin-a-b-inhibitors-highlighted-in-poster-presentations-at-american-association-for-cancer-research-annual-meeting\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Circle Pharma\u2019s first-in-class orally bioavailable macrocyclic cyclin A\/B inhibitors highlighted in poster presentations at American Association for Cancer Research Annual Meeting - Pharma Trend\" \/>\n<meta property=\"og:description\" content=\"Data show activity across a wide range of human tumor cell lines Tumor regression observed in xenograft models of small cell lung cancer and ovarian cancer Research from the laboratory of Dr. Matthew Oser at the Dana Farber Cancer Institute identified the key role of the SAC complex in selective tumor cell killing by cyclin ... 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