[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-331711-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-331711-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","targeting-mao-b-with-small-molecule-inhibitors-a-decade-of-advances-in-anticancer-research-20122024","Targeting MAO-B with Small-Molecule Inhibitors - A Decade of Advances in Anticancer Research (2012–2024)","","Monoamine oxidase B (MAO-B) is a key mitochondrial outer-membrane enzyme responsible for oxidative deamination of biogenic amines. Its overexpression contributes to multiple cancers, including glioblastoma and colorectal, lung, renal, and bladder tumors, through increased reactive oxygen species (ROS). MAO-B inhibition can reduce cell proliferation and support apoptosis, making it a therapeutic target. This review integrates MAO-B network biology, molecular modeling of ligand binding, and summarizes MAO-B inhibitors reported from 2012–2024. It highlights major molecular scaffolds, such as propargyl analogs of phenyl alkyl amines, hydrazine derivatives, cyclopropylamine derivatives, MAO-B-activated pro-drugs, and natural phenylpropanoid derivatives, emphasizing their anticancer potential.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/targeting-mao-b-with-small-molecule-inhibitors-a-decade-of-advances-in-anticancer-research-20122024/331711/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/targeting-mao-b-with-small-molecule-inhibitors-a-decade-of-advances-in-anticancer-research-20122024/331711.png","ImageObject",300,407,{"name":42,"@type":43},"Aurelia","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-03","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",8,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why is MAO-B considered a relevant target for anticancer therapy?","Question",{"text":63,"@type":64},"MAO-B overexpression is implicated in several cancers, partly via elevated reactive oxygen species (ROS). Inhibiting MAO-B can impede cell proliferation and supports its potential as a therapeutic target.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What roles do MAO-B ligand-binding features and key residues play?",{"text":68,"@type":64},"Molecular modeling indicates a hydrophobic binding pocket for MAO-B ligands, with critical residues such as Tyr398 and Tyr435 involved in substrate oxidation.",{"name":70,"@type":61,"acceptedAnswer":71},"Which MAO-B inhibitor scaffold types are discussed for 2012–2024?",{"text":72,"@type":64},"The review summarizes reported inhibitors including propargyl analogs of phenyl alkyl amines, hydrazine derivatives, cyclopropylamine derivatives, MAO-B-activated pro-drugs, and natural phenylpropanoid derivatives.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},331711,1790293300,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,111,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":108,"show_sort_weight":109,"slug":110},7,"Healthcare",40,"healthcare",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":112,"slug":113},30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":55,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145,"preview_page_count":4},1099514068365,"https://ap-avatar.wpscdn.com/avatar/10000253d8d9f28188e?x-image-process=image/resize,m_fixed,w_180,h_180&k=1794309523707217728","Review  \nTargeting MAO-B with Small-Molecule Inhibitors: A Decade of Advances in Anticancer Research (2012–2024)  \nIyman Alsaad 1, Diana M. A. Abdel Rahman 1, Ola Al-Tamimi 1, Shayma’a A. Alhaj 1, Dima A. Sabbah 2, Rima Hajjo 2,3,4 and Sanaa K. Bardaweel 1, *  \nAcademic Editor: Athanassios  \nC. Tsipis  \nReceived: 13 November 2024  \nRevised: 17 December 2024  \nAccepted: 26 December 2024  \nPublished: 31 December 2024  \nCitation: Alsaad, I.; Abdel Rahman, D.M.A.; Al-Tamimi, O.; Alhaj, S.A.; Sabbah, D.A.; Hajjo, R.; Bardaweel, S.K. Targeting MAO-B with  \nSmall-Molecule Inhibitors: A Decade of Advancesin Anticancer Research (2012–2024). Molecules 2025, 30, 126 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)molecules30010126  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) .  \n1 Department of Pharmaceutical Sciences, School of Pharmacy, University of Jordan, Amman 11942, Jordan; [olatameemi@gmail.com](olatameemi@gmail.com) (O.A.-T.)  \n2 Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733, Jordan; [dima.sabbah@zuj.edu.jo](dima.sabbah@zuj.edu.jo) (D.A.S.); [r.hajjo@zuj.edu.jo](r.hajjo@zuj.edu.jo) (R.H.)  \n3 Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA  \n4 Jordan CDC, Amman 11118, Jordan  \n* Correspondence: [s.bardaweel@ju.edu.jo](s.bardaweel@ju.edu.jo)  \nAbstract: Monoamine oxidase B (MAO-B) is a key enzyme in the mitochondrial outer membrane, pivotal for the oxidative deamination of biogenic amines. Its overexpression has been implicated in the pathogenesis of several cancers, including glioblastoma and colorectal, lung, renal, and bladder cancers, primarily through the increased production of reactive oxygen species (ROS) . Inhibition of MAO-B impedes cell proliferation, making it a potential therapeutic target. Various monoamine oxidase B inhibitors have shown promise in inhibiting tumor growth and inducing apoptosis across different cancer types. In this review, we investigate MAO-B network biology, which highlighted glycolysis pathways as notable links between MAO-B and cancer. Further molecular modeling analysis illustrated the basis of MAO-B ligand binding, revealing a hydrophobic binding pocket, with key residues such as Tyr398 and Tyr435 playing crucial roles in substrate oxidation. MAO-B inhibitors that were reportsed in the literature (2012–2024) and their potential application in cancer therapy were discussed, highlighting key molecular scaffolds, such as propargyl analogs of phenyl alkyl amines, hydrazine derivatives, cyclopropylamine derivatives, MAO-B activated pro-drugs, and natural phenylpropanoid derivatives. The reported literature underscores the therapeutic potential of MAO-B inhibitors as versatile anticancer agents, warranting further investigation to optimize their efficacy and specificity across various malignancies.  \nKeywords: cancer; monoamine oxidase B (MAO-B); MAO-B inhibitors; MAO-B network biology; MAO-B ligand interactions; anticancer agents  \n1. Introduction  \nMonoamine oxidase (MAO), also referred to as tyramine oxidase, is a FAD-dependent enzyme that is located at the mitochondrial outer membrane [1,2] . It catalyzes the oxidative deamination of biogenic amines such as monoamine neurotransmitters (serotonin, dopamine, and norepinephrine) and dietary amines [2–5] . MAO enzymes have the covalently bound flavin adenine (FAD) cofactor that is essential for their enzymatic activity [3] . There are two isoforms of monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidas","cbCaicxZrHcJn9Ft","https://ap.wps.com/l/cbCaicxZrHcJn9Ft","pdf",3380347,22,"English","# Abstract\n# Introduction\n## MAO enzymes: location, function, and isoforms\n## MAO-B regulation and structural features\n# Targeting MAO-B in anticancer drug discovery\n## Rationale for small-molecule inhibitors","[{\"question\":\"Why is MAO-B considered a relevant target for anticancer therapy?\",\"answer\":\"MAO-B overexpression is implicated in several cancers, partly via elevated reactive oxygen species (ROS). Inhibiting MAO-B can impede cell proliferation and supports its potential as a therapeutic target.\"},{\"question\":\"What roles do MAO-B ligand-binding features and key residues play?\",\"answer\":\"Molecular modeling indicates a hydrophobic binding pocket for MAO-B ligands, with critical residues such as Tyr398 and Tyr435 involved in substrate oxidation.\"},{\"question\":\"Which MAO-B inhibitor scaffold types are discussed for 2012–2024?\",\"answer\":\"The review summarizes reported inhibitors including propargyl analogs of phenyl alkyl amines, hydrazine derivatives, cyclopropylamine derivatives, MAO-B-activated pro-drugs, and natural phenylpropanoid derivatives.\"}]","Targeting MAO-B with Small-Molecule Inhibitors - A Decade of Advances in Anticancer Research (2012–2024) | PDF",1789994803,55]