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Cholesterol efflux is measured in THP-1 macrophages and in diabetes patients before and after MN-001 dosing. MN-002 increases ABCA1-mediated efflux and ABCA1/ABCG1 expression independently of PKA, while neither compound improves HDL-mediated efflux. Docking suggests PPAR-alpha binding as a plausible mechanism.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/enhancement-of-abca1-and-abcg1-expression-and-cholesterol-efflux-by-a-metabolite-of-tipelukast-a-potential-therapeutic-strategy-for-atherosclerosis/459446/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/enhancement-of-abca1-and-abcg1-expression-and-cholesterol-efflux-by-a-metabolite-of-tipelukast-a-potential-therapeutic-strategy-for-atherosclerosis/459446.png","ImageObject",300,407,{"name":92,"@type":93},"Valentina","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-09","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What was the main aim of the study on MN-001 and MN-002?","Question",{"text":112,"@type":113},"To determine whether MN-001 and its active metabolite MN-002 enhance cholesterol efflux via ABCA1 and ABCG1, thereby reducing foam cell formation, and to assess cholesterol efflux capacity in diabetes patients before and after MN-001 administration.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How did MN-002 affect ABCA1- and ABCG1-mediated cholesterol efflux?",{"text":117,"@type":113},"MN-002 enhanced ABCA1-mediated cholesterol efflux, upregulated ABCA1 expression independently of PKA, and increased ABCG1 expression. It did not influence HDL-mediated efflux.",{"name":119,"@type":110,"acceptedAnswer":120},"What mechanism did molecular docking suggest for MN-002?",{"text":121,"@type":113},"Molecular docking simulations indicated that MN-002 may bind to PPAR-alpha, supporting a potential mechanism for its effects on cholesterol metabolism.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},459446,1791098790,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},13056703020460,"https://ap-avatar.wpscdn.com/avatar/be000253dac470eee5d?_k=1778207105932848923","The official journal of the Japan Atherosclerosis Society and  \nthe Asian Pacific Society of Atherosclerosis and Vascular Diseases  \nOriginal Article  \nJ Atheroscler Thromb, 2026; 33: 55-77. [http://doi.org/10.5551/jat.65669](http://doi.org/10.5551/jat.65669)  \nEnhancement of ABCA1 and ABCG1 Expression and Cholesterol Efflux by a Metabolite of Tipelukast: A Potential Therapeutic Strategy for Atherosclerosis  \nHuicheng Qi 1 , 2 , Masatsune Ogura 2 , Kazuko Matsuda 1 and Takashi Miida 2  \n1 MediciNova,Inc, La Jolla,California, USA  \n2 Department of Clinical Laboratory Technology, Faculty of Medical Science, Juntendo University, Chiba, Japan  \nAims: MN-001 (tipelukast), a compound with lipid-modulating and anti-inflammatory properties, and its active metabolite MN-002, have been suggested to influence cholesterol metabolism. This study aimed to investigate whether MN-001 and MN-002 enhance cholesterol efflux via ABCA1 and ABCG1, thereby reducing foam cell formation. We also evaluated cholesterol efflux capacity in patients with diabetes before and after MN-001 administration.  \nMethods: Cholesterol efflux was assessed in THP-1 macrophages treated with MN-001 and MN-002 in the presence of ApoA-I or HDL. ABCA1 and ABCG1 expression were evaluated using western blot and qPCR analyses. A 12-week observational study in patients with diabetes evaluated the cholesterol efflux capacity using ApoB-depleted serum and radiolabeled J774.1 macrophages. Molecular docking simulations were conducted to explore MN-002 binding affinities, aiming to identify potential target proteins and elucidate the molecular mechanisms underlying their effects on cholesterol metabolism.  \nResults: MN-002 enhanced ABCA1-mediated cholesterol efflux and upregulated ABCA1 expression independently of PKA. It also increased ABCG1 expression; however, neither MN-001 nor MN-002 influenced HDL-mediated efflux. MN-001 showed no significant improvement in cholesterol efflux capacity (p = 0.6507) inpatients with diabetes. Molecular docking simulations indicated that MN-002 may bind to PPAR-alpha, suggesting a potential mechanism for its effects.  \nConclusion: MN-002 offers a novel therapeutic approach for atherosclerosis by upregulating ABCA1 and ABCG1 expression and enhancing ApoA-I-mediated cholesterol efflux. Further studies are required to clarify the underlying mechanisms and assess their clinical potential in atherosclerosis and metabolic disorders.  \nSee editorial vol. 33: 26-28  \nKey words: Tipelukast, Macrophages, ABCA1, Cholesterol efflux, Atherosclerosis  \n\n| Introduction\u003Cbr>Atherosclerotic cardiovascular diseases (ASCVD) remain a leading cause of mortality in developed countries, primarily driven by dyslipidemia and chronic inflammation 1-3) . Low-density lipoprotein cholesterol (LDL-C) is a well-established major risk factor for ASCVD, and LDL-C-lowering therapies, such as statins, have significantly reduced the incidence and mortality associated with ASCVD 1, 2) . | However, even with optimal LDL-C reduction, a substantial residual risk persists. This residual risk is driven by factors such as elevated triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C) levels, and chronic inflammation, which contribute to the progression of atherosclerosis 4-6) .\u003Cbr>Addressing this residual risk requires therapeutic strategies beyond lowering the LDL-C levels. Targeting the alternative pathways involved in lipid metabolism and inflammation is essential for |\n| --- | --- |\n\nAddress for correspondence: Huicheng Qi, MediciNova, Inc., 4275 Executive Square, Suite 300, La Jolla, California 92037, USA E-mail: [sai@medicinova.com](sai@medicinova.com)  \n[Received: January 30](Received: January 30) , 2025 Accepted for publication: June 11, 2025  \nCopyright©2026 Japan Atherosclerosis Society  \nThis article is distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License.  \nadvancing ASCVD management 7, 8) . Therapie","cbCaiqML5GOMdvpr","https://ap.wps.com/l/cbCaiqML5GOMdvpr","pdf",2639614,23,"English","# Introduction\n## Residual ASCVD risk beyond LDL-C reduction\n## Macrophage cholesterol efflux and foam cell prevention\n## Regulation by ABCA1/ABCG1 and nuclear receptors\n# Methods\n## Cellular efflux assays in THP-1 macrophages\n## ABCA1 and ABCG1 expression analysis\n## 12-week observational study in diabetes patients\n## Molecular docking for MN-002 targets\n# Results\n## Effects of MN-001 and MN-002 on efflux pathways\n## Effects on transporter expression\n## Clinical efflux outcome after MN-001\n## Docking-based target prediction\n# Conclusion","[{\"question\":\"What was the main aim of the study on MN-001 and MN-002?\",\"answer\":\"To determine whether MN-001 and its active metabolite MN-002 enhance cholesterol efflux via ABCA1 and ABCG1, thereby reducing foam cell formation, and to assess cholesterol efflux capacity in diabetes patients before and after MN-001 administration.\"},{\"question\":\"How did MN-002 affect ABCA1- and ABCG1-mediated cholesterol efflux?\",\"answer\":\"MN-002 enhanced ABCA1-mediated cholesterol efflux, upregulated ABCA1 expression independently of PKA, and increased ABCG1 expression. It did not influence HDL-mediated efflux.\"},{\"question\":\"What mechanism did molecular docking suggest for MN-002?\",\"answer\":\"Molecular docking simulations indicated that MN-002 may bind to PPAR-alpha, supporting a potential mechanism for its effects on cholesterol metabolism.\"}]","Enhancement of ABCA1 and ABCG1 Expression and Cholesterol Efflux by a Metabolite of Tipelukast - A Potential Therapeutic Strategy for Atherosclerosis | PDF",1790755945,58]