Gao, Yongzhi van Haren, Matthijs J Buijs, Ned Innocenti, Paolo Zhang, Yurui Sartini, Davide Campagna, Roberto Emanuelli, Monica Parsons, Richard B Jespers, Willem
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Published in
Journal of medicinal chemistry
Nicotinamide N-methyltransferase (NNMT) methylates nicotinamide (vitamin B3) to generate 1-methylnicotinamide (MNA). NNMT overexpression has been linked to a variety of diseases, most prominently human cancers, indicating its potential as a therapeutic target. The development of small-molecule NNMT inhibitors has gained interest in recent years, wi...
Marcinkowska, Monika Bucki, Adam Sniecikowska, Joanna Zagórska, Agnieszka Fajkis-Zajączkowska, Nikola Siwek, Agata Gluch-Lutwin, Monika Żmudzki, Paweł Jastrzebska-Wiesek, Magdalena Partyka, Anna
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Published in
Journal of medicinal chemistry
The current pharmaceutical market lacks therapeutic agents designed to modulate behavioral disturbances associated with dementia. To address this unmet medical need, we designed multifunctional ligands characterized by a nanomolar affinity for clinically relevant targets that are associated with the disease pathology, namely, the 5-HT2A/6/7 and D2 ...
Jin, Chunyang
Published in
Journal of medicinal chemistry
Peukert, Carsten Langer, Laura N B Wegener, Sophie M Tutov, Anna Bankstahl, Jens P Karge, Bianka Bengel, Frank M Ross, Tobias L Brönstrup, Mark
Published in
Journal of medicinal chemistry
The diagnosis of bacterial infections at deep body sites benefits from noninvasive imaging of molecular probes that can be traced by positron emission tomography (PET). We specifically labeled bacteria by targeting their iron transport system with artificial siderophores. The cyclen-based probes contain different binding sites for iron and the PET ...
Li, Xiangqian Li, Xiaowei Liu, Fang Li, Shuo Shi, Dayong
Published in
Journal of medicinal chemistry
The development of multitarget-directed ligands (MTDLs) has become a widely focused research topic, but rational design remains as an enormous challenge. This paper reviews and discusses the design strategy of incorporating the second activity into an existing single-active ligand. If the binding sites of both targets share similar endogenous subst...
Konno, Sho Kobayashi, Kiyotaka Senda, Miki Funai, Yuta Seki, Yuta Tamai, Ikumi Schäkel, Laura Sakata, Kyousuke Pillaiyar, Thanigaimalai Taguchi, Akihiro
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Published in
Journal of medicinal chemistry
The novel coronavirus, SARS-CoV-2, has been identified as the causative agent for the current coronavirus disease (COVID-19) pandemic. 3CL protease (3CLpro) plays a pivotal role in the processing of viral polyproteins. We report peptidomimetic compounds with a unique benzothiazolyl ketone as a warhead group, which display potent activity against SA...
de Gaetano, Monica Tighe, Catherine Gahan, Kevin Zanetti, Andrea Chen, Jianmin Newson, Justine Cacace, Antonino Marai, Mariam Gaffney, Andrew Brennan, Eoin
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Published in
Journal of medicinal chemistry
Failure to resolve inflammation underlies many prevalent pathologies. Recent insights have identified lipid mediators, typified by lipoxins (LXs), as drivers of inflammation resolution, suggesting potential therapeutic benefit. We report the asymmetric preparation of novel quinoxaline-containing synthetic-LXA4-mimetics (QNX-sLXms). Eight novel comp...
Ren, Chaowei Sun, Ning Liu, Haixia Kong, Ying Sun, Renhong Qiu, Xing Chen, Jinju Li, Yan Zhang, Jianshui Zhou, Yuedong
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Published in
Journal of medicinal chemistry
Proteolysis-targeting chimera (PROTAC) is an attractive technology in drug discovery. Canonically, targets act as a basic starting point in the most previous PROTAC design. Here, we designed degraders considering from the view of clinical benefits. With this novel design, Brigatinib was turned into a degrader SIAIS164018 and endowed with unique fea...
van der Westhuyzen, Renier Mabhula, Amanda Njaria, Paul M Müller, Rudolf Ngumbu Muhunga, Denis Taylor, Dale Lawrence, Nina Njoroge, Mathew Brunschwig, Christel Moosa, Atica
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Published in
Journal of medicinal chemistry
Screening of a library of small polar molecules against Mycobacterium tuberculosis (Mtb) led to the identification of a potent benzoheterocyclic oxime carbamate hit series. This series was subjected to medicinal chemistry progression underpinned by structure-activity relationship studies toward identifying a compound for proof-of-concept studies an...
Liu, Kongjun Li, Dan Zheng, Wei Shi, Mingsong Chen, Yong Tang, Minghai Yang, Tao Zhao, Min Deng, Dexin Zhang, Chufeng
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Published in
Journal of medicinal chemistry
Guided by molecular docking, a commonly used open-chain linker was cyclized into a five-membered pyrrolidine to lock the overall conformation of the propeller-shaped molecule. Different substituents were introduced into the pyrrolidine moiety to block oxidative metabolism. Surprisingly, it was found that a small methyl substituent could be used to ...
