Rebecca A. Gallego*, Stephanie Scales, Chad Toledo, Marin Auth, Louise Bernier, Madeline Berry, Sonja Brun, Loanne Chung, Carl Davis, Wade Diehl, Klaus Dress, Koleen Eisele, Jeff Elleraas, Jason Ewanicki, Yvette Fobian, Samantha Greasley, Eric C. Greenwald, Ted W. Johnson, Penney Khamphavong, Jennifer Lafontaine, Jian Li, Angelica Linton, Michael Maestre, Nichol Miller, Anwar Murtaza, Ryan L. Patman, Casey L. Quinlan, Dana J. Ramms, Paul Richardson, Neal Sach, Romelia Salomon-Ferrer, Francisco Silva, Sergei Timofeevski, Phuong Tran, Michelle Tran-Dubé, Fen Wang, Wei Wang, Martin Wythes, Shouliang Yang, Aihua Zou, Todd VanArsdale and Indrawan McAlpine*,
{"title":"Discovery of Highly Selective Inhibitors of Microtubule-Associated Serine/Threonine Kinase-like (MASTL)","authors":"Rebecca A. Gallego*, Stephanie Scales, Chad Toledo, Marin Auth, Louise Bernier, Madeline Berry, Sonja Brun, Loanne Chung, Carl Davis, Wade Diehl, Klaus Dress, Koleen Eisele, Jeff Elleraas, Jason Ewanicki, Yvette Fobian, Samantha Greasley, Eric C. Greenwald, Ted W. Johnson, Penney Khamphavong, Jennifer Lafontaine, Jian Li, Angelica Linton, Michael Maestre, Nichol Miller, Anwar Murtaza, Ryan L. Patman, Casey L. Quinlan, Dana J. Ramms, Paul Richardson, Neal Sach, Romelia Salomon-Ferrer, Francisco Silva, Sergei Timofeevski, Phuong Tran, Michelle Tran-Dubé, Fen Wang, Wei Wang, Martin Wythes, Shouliang Yang, Aihua Zou, Todd VanArsdale and Indrawan McAlpine*, ","doi":"10.1021/acs.jmedchem.4c0165910.1021/acs.jmedchem.4c01659","DOIUrl":null,"url":null,"abstract":"<p >By virtue of its role in cellular proliferation, microtubule-associated serine/threonine kinase-like (MASTL) represents a novel target and a first-in-class (FIC) opportunity to provide a new impactful therapeutic agent to oncology patients. Herein, we describe a hit-to-lead optimization effort that resulted in the delivery of two highly selective MASTL inhibitors. Key strategies leveraged to enable this work included structure-based drug design (SBDD), analysis of lipophilic efficiency (LipE) and novel synthesis. The resulting advanced lead compounds enabled a tumor growth inhibition study which was pivotal in assessing the potential value of MASTL as an oncology therapeutic target.</p>","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"67 21","pages":"19234–19246 19234–19246"},"PeriodicalIF":6.8000,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.jmedchem.4c01659","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
By virtue of its role in cellular proliferation, microtubule-associated serine/threonine kinase-like (MASTL) represents a novel target and a first-in-class (FIC) opportunity to provide a new impactful therapeutic agent to oncology patients. Herein, we describe a hit-to-lead optimization effort that resulted in the delivery of two highly selective MASTL inhibitors. Key strategies leveraged to enable this work included structure-based drug design (SBDD), analysis of lipophilic efficiency (LipE) and novel synthesis. The resulting advanced lead compounds enabled a tumor growth inhibition study which was pivotal in assessing the potential value of MASTL as an oncology therapeutic target.
期刊介绍：
The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents.
The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.
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