Article
Pharmacology & Pharmacy
Rintaro Kato, Wenyu Zeng, Vishal B. Siramshetty, Jordan Williams, Md Kabir, Natalie Hagen, Elias C. Padilha, Amy Q. Wang, Ewy A. Mathe, Xin Xu, Pranav Shah
Summary: Efficiently overcoming the blood-brain barrier is a major challenge in drug development for the central nervous system. In this study, researchers used a large dataset of compounds to develop a machine learning model for predicting the permeability of small molecules across the blood-brain barrier. The model showed high accuracy and was validated through correlation analysis with in vivo data. This research offers valuable resources for the drug discovery community.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Michael J. Wheadon, Craig A. Townsend
Summary: This research reports the synthesis and application of a compound that forms irreversible cross-links with engineered thiol nucleophiles in the active site of condensation domains, aiming to stabilize the interactions between condensation domains and their substrates or client domains in nonribosomal peptide synthetases (NRPSs). The compound demonstrates high synthetic tractability and provides a feasible tactic for stabilizing condensation domain interactions in multidomain NRPS fragments.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Georgi Stavrakov, Irena Philipova, Atanas Lukarski, Mariyana Atanasova, Borislav Georgiev, Teodora Atanasova, Spiro Konstantinov, Irini Doytchinova
Summary: Despite the lack of effective treatment for neurodegenerative diseases, AChE inhibitors remain important in the symptomatic treatment of mild to moderate cognitive impairments. Researchers designed a new library of AChE inhibitors and found a more effective non-toxic compound through virtual screening.
Review
Chemistry, Multidisciplinary
Nathan J. Castellino, Andrew P. Montgomery, Jonathan J. Danon, Michael Kassiou
Summary: The development of late-stage functionalization (LSF) methodologies, particularly C-H functionalization, has had a revolutionary impact on organic synthesis. In recent years, medicinal chemists have incorporated LSF strategies into their drug discovery programs to improve efficiency. This review comprehensively surveys the latest progress in utilizing LSF techniques to enhance drug-like molecular properties, highlighting case studies and commenting on the potential transformative role of LSF in drug discovery.
Article
Biochemistry & Molecular Biology
Thuy Nguyen, Nadezhda German, Ann M. Decker, Jun-Xu Li, Jenny L. Wiley, Brian F. Thomas, Terry P. Kenakin, Yanan Zhang
BIOORGANIC & MEDICINAL CHEMISTRY
(2015)
Review
Chemistry, Medicinal
Thuy Nguyen, Jun-Xu Li, Brian F. Thomas, Jenny L. Wiley, Terry P. Kenakin, Yanan Zhang
MEDICINAL RESEARCH REVIEWS
(2017)
Article
Chemistry, Medicinal
Thuy Nguyen, Nadezhda German, Ann M. Decker, Tiffany L. Langston, Thomas F. Gamage, Charlotte E. Farquhar, Jun-Xu Li, Jenny L. Wiley, Brian F. Thomas, Yanan Zhang
JOURNAL OF MEDICINAL CHEMISTRY
(2017)
Article
Neurosciences
Thomas E. Gamage, Charlotte E. Farquhar, Timothy W. Lefever, Brian F. Thomas, Thuy Nguyen, Yanan Zhang, Jenny L. Wiley
Article
Chemistry, Organic
David Perrey, Dehui Zhang, Thuy Nguyen, F. Ivy Carroll, Mei-Chuan Ko, Yanan Zhang
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2018)
Article
Chemistry, Medicinal
Haiyan Yang, Lohitha Rao Chennamaneni, Melvyn Wai Tuck Ho, Shi Hua Ang, Eldwin Sum Wai Tan, Duraiswamy Athisayamani Jeyaraj, Yoon Sheng Yeap, Boping Liu, Esther Hq Ong, Joma Kanikadu Joy, John Liang Kuan Wee, Perlyn Kwek, Priya Retna, Nurul Dinie, Thuy Thi Hanh Nguyen, Shi Jing Tai, Vithya Manoharan, Vishal Pendharkar, Choon Bing Low, Yun Shan Chew, Susmitha Vuddagiri, Kanda Sanfthongpitag, Meng Ling Choong, May Ann Lee, Srinivasaraghavan Kannan, Chandra S. Verma, Anders Poulsen, Sharon Lim, Charles Chuah, Tiong Sin Ong, Jeffrey Hill, Alex Matter, Kassoum Nacro
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Biochemistry & Molecular Biology
Thuy Nguyen, Thomas F. Gamage, Ann M. Decker, Nadezhda German, Tiffany L. Langston, Charlotte E. Farquhar, Terry P. Kenakin, Jenny L. Wiley, Brian F. Thomas, Yanan Zhang
ACS CHEMICAL NEUROSCIENCE
(2019)
Article
Chemistry, Medicinal
Jenson Verghese, Thuy Nguyen, Lisa M. Oppegard, Lauren M. Seivert, Hiroshi Hiasa, Keith C. Ellis
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2013)
Article
Chemistry, Medicinal
Sudha Korwar, Thuy Nguyen, Keith C. Ellis
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2014)
Article
Chemistry, Medicinal
Thuy Nguyen, Tianming Yang, Mei-Lin Go
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2014)
Article
Biochemistry & Molecular Biology
Gareth K. Jennings, Anuja Modi, Justin E. Elenewski, Caroline M. Ritchie, Thuy Nguyen, Keith C. Ellis, John C. Hackett
JOURNAL OF INORGANIC BIOCHEMISTRY
(2014)
Article
Plant Sciences
Lisa M. Oppegard, Thuy Nguyen, Keith C. Ellis, Hiroshi Hiasa
JOURNAL OF NATURAL PRODUCTS
(2012)
Article
Chemistry, Medicinal
Lauren M. Gaskell, Thuy Nguyen, Keith C. Ellis
MEDICINAL CHEMISTRY RESEARCH
(2014)
Article
Chemistry, Medicinal
Thuy Nguyen, Robert A. Coover, Jenson Verghese, Richard G. Moran, Keith C. Ellis
ACS MEDICINAL CHEMISTRY LETTERS
(2014)
Article
Biochemistry & Molecular Biology
Thuy Nguyen, Ann M. Decker, Tiffany L. Langston, Kelly M. Mathews, Justin N. Siemian, Jun-Xu Li, Danni L. Harris, Scott P. Runyon, Yanan Zhang
ACS CHEMICAL NEUROSCIENCE
(2017)
Article
Chemistry, Medicinal
Shuang Mei, Su Jiang, Yuting Wang, Han Jing, Peng Yang, Miao-Miao Niu, Jindong Li, Kai Yuan, Yan Zhang
Summary: This study identifies a dual-targeting peptide, AP-1, that effectively inhibits variants of concern (VOCs) of SARS-CoV-2 without impairing host cell viability. The findings suggest that AP-1 could be a promising broad-spectrum agent for treating emerging VOCs of SARS-CoV-2.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Hyeonjun Lee, Ju Yeon Lee, Hyunsoo Jang, Hye Young Cho, Minhee Kang, Sang Hyun Bae, Suin Kim, Eunji Kim, Jaebong Jang, Jin Young Kim, Young Ho Jeon
Summary: By using liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance experiments, we identified new chemical moieties that bind to the target sites of the protein of interest, allowing for reversible binding and protein degradation. This method has the potential to expand the application of PROTAC technology.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Yingying Li, Xiyou Du, Xinru Kong, Yuelin Fang, Zhijing He, Dongzhu Liu, Hang Wu, Jianbo Ji, Xiaoye Yang, Lei Ye, Guangxi Zhai
Summary: This study proposes a novel nanoplatform based on the autophagy cascade to overcome the obstacles in chemo-immunotherapy. The platform combines chemotherapy and starvation therapy to initiate pro-death autophagy and enhance antigen presentation, while also remodeling the immunosuppressive tumor microenvironment. Furthermore, the study discovers a new therapeutic direction for the respiration inhibitor 3-bromopyruvic acid (3BP) in cancer treatment. Overall, this study offers an opportunity to improve antitumor efficacy and boost immune responses.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Bingsi Wang, Mingxu Ma, Yusen Dai, Pengfei Yu, Liang Ye, Wenyan Wang, Chunjie Sha, Huijie Yang, Yingjie Yang, Yunjing Zhu, Lin Dong, Shujuan Wei, Linlin Wang, Jingwei Tian, Hongbo Wang
Summary: Breast cancer is a common malignant tumor in women, and drug resistance remains a clinical challenge. In this study, a novel compound, G-5b, was developed with potent antagonistic and degradation activities comparable to the current drug fulvestrant. G-5b also showed improved stability and solubility. Mechanistically, G-5b engages the proteasome pathway to degrade ER, inhibiting the ER signaling pathway and inducing apoptosis and cell cycle arrest. In animal models, G-5b exhibited superior pharmacokinetics and pharmacodynamics properties. Overall, G-5b is a promising long-acting SERD worthy of further investigation and optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Karoline B. Waitman, Larissa C. de Almeida, Marina C. Primi, Jorge A. E. G. Carlos, Claudia Ruiz, Thales Kronenberger, Stefan Laufer, Marcia Ines Goettert, Antti Poso, Sandra V. Vassiliades, Vinicius A. M. de Souza, Monica F. Z. J. Toledo, Neuza M. A. Hassimotto, Michael D. Cameron, Thomas D. Bannister, Leticia Costa-Lotufo, Joa o A. Machado-Neto, Mauricio T. Tavares, Roberto Parise-Filho
Summary: A series of hybrid inhibitors combining pharmacophores of known kinase inhibitors and benzohydroxamate HDAC inhibitors were synthesized and evaluated for their anticancer activity and pharmacokinetic properties. Compounds 4d-f exhibited promising cytotoxicity against hematological cells and moderate activity against solid tumor models. Compound 4d showed potent inhibition of multiple kinase targets and had stable interactions with HDAC and members of the JAK family. These compounds showed selective cytotoxicity with minimal effects on non-tumorigenic cells and favorable pharmacokinetic profiles.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Michal Sulik, Diana Fontinha, Dietmar Steverding, Szymon Sobczak, Michal Antoszczak, Miguel Prudencio, Adam Huczynski
Summary: This study describes the synthesis of the first-in-class ivermectin derivatives obtained through derivatization of the C13 position, along with the unexpected rearrangement of the macrolide ring. These derivatives show potential for antiparasitic activity and are important for the development of new antiparasitic agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Jun Liu, Qiu-Xian Chen, Wen-Fu Wu, Dong Wang, Si -Yu Zhao, Jia-Hao Li, Yi-Qun Chang, Shao-Gao Zeng, Jia-Yi Hu, Yu-Jie Li, Jia-Xin Du, Shu-Meng Jiao, Hai-Chuan Xiao, Qiang Zhang, Jun Xu, Jian-Fu Zhao, Hai -Bo Zhou, Yong-Heng Wang, Jian Zou, Ping-Hua Sun
Summary: A new anti-infective drug strategy has been discovered to attenuate virulence and modulate inflammation caused by drug-resistant Pseudomonas aeruginosa infections. Compound 5f inhibits biofilm formation, macrophage migration, and inflammatory response induced by P. aeruginosa, showing potential as a novel candidate against drug-resistant infections.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Liuzeng Chen, Ke Wang, Lingyun Wang, Wei Wang, Lifan Wang, Jia Li, Xiaohan Liu, Mengya Wang, Banfeng Ruan
Summary: In this study, a series of novel anti-inflammatory compounds were designed and synthesized based on the natural product pterostilbene skeleton. Among them, compound 8 showed the highest activity and exhibited its effects through inhibition of pro-inflammatory cytokines by blocking the NF-KB/MAPK signaling pathway. Compound 8 also demonstrated a good relieving effect on acute colitis in mice and showed good safety in acute toxicity experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Si-Min Liang, Gui-Bin Liang, Hui-Ling Wang, Hong Jiang, Xian-Li Ma, Jian-Hua Wei, Ri-Zhen Huang, Ye Zhang
Summary: A series of novel multi-target antitumor agents were designed, synthesized, and evaluated. Some compounds exhibited significant antitumor activity and one compound showed excellent efficacy, limited toxicity, and low resistance. Further mechanism studies revealed that the compound exerted antitumor effects through multiple pathways.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)