Article
Chemistry, Medicinal
Ming-Hsiu Yang, Jamie L. Russell, Yuto Mifune, Ying Wang, Hexin Shi, Eva Marie Y. Moresco, Daniel J. Siegwart, Bruce Beutler, Dale L. Boger
Summary: Diprovocims are a new class of TLR agonists that act through the TLR1/TLR2 mechanism, exhibit structure-activity relationships, and have in vivo adjuvant activity. They have potent agonist activity towards human TLR1/TLR2 and can be functionalized without impacting this activity. Improvement in potency and efficacy in the murine system has also been achieved.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Alice Shi Ming Li, Serah Kimani, Brian Wilson, Mahmoud Noureldin, Hector Gonzalez-Alvarez, Ahmed Mamai, Laurent Hoffer, John P. Guilinger, Ying Zhang, Moritz von Rechenberg, Jeremy S. Disch, Christopher J. Mulhern, Belinda L. Slakman, John W. Cuozzo, Aiping Dong, Gennady Poda, Mohammed Mohammed, Punit Saraon, Manish Mittal, Prati k Modh, Vaibhavi Rathod, Bhashant Patel, Suzanne Ackloo, Vijayaratnam Santhakumar, Magdalena M. Szewczyk, Dalia Barsyte-Lovejoy, Cheryl H. Arrowsmith, Richard Marcellus, Marie-Aude Guie, Anthony D. Keefe, Peter J. Brown, Levon Halabelian, Rima Al-awar, Masoud Vedadi
Summary: DCAF1 is a substrate receptor for two E3 ligases and has critical physiological role in protein degradation, making it a potential drug target for cancer and viral treatments. By screening a large compound library and conducting hit optimization, a compound called OICR-8268 was discovered as a tool compound for the development of DCAF1 ligands for cancer therapeutics. OICR-8268 showed strong target engagement and can be used for further investigation of DCAF1 functions and the development of DCAF1-based PROTACs.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Pharmacology & Pharmacy
D. Sala, H. Batebi, K. Ledwitch, P. W. Hildebrand, J. Meiler
Summary: The use of deep machine learning in protein structure prediction allows easy access to annotated conformations, which can compensate for missing experimental structures in structure-based drug discovery. However, the accuracy of these predicted conformations for screening chemical compounds that effectively interact with protein targets is still uncertain. This opinion article examines the benefits and limitations of using state-annotated conformations for ultra-large library screening, particularly for common drug targets like G-protein-coupled receptors.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2023)
Article
Medicine, Research & Experimental
Seoyeon Jeong, Hwa-Ryeon Kim, June-Ha Shin, Min-Hee Son, In-Hyun Lee, Jae-Seok Roe
Summary: Researchers used DNA-encoded library screening to identify BBC1115 as a selective BET inhibitor that suppresses aberrant cell fate programs. BBC1115 impaired proliferation in various cancer cells and inhibited tumor growth with minimal toxicity in vivo. This study demonstrates that integrating DEL screening and biological validation is a reliable strategy for discovering new compounds targeting proteins involved in epigenetic regulation in human malignancies.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Biochemistry & Molecular Biology
Ye Han, Iredia D. Iyamu, Matthew R. Clutter, Rama K. Mishra, Kyle A. Lyman, Chengwen Zhou, Ioannis Michailidis, Maya Y. Xia, Horrick Sharma, Chi-Hao Luan, Gary E. Schiltz, Dane M. Chetkovich
Summary: Major depressive disorder is a critical public health problem with a high prevalence in the United States. Researchers have discovered that disrupting the interaction between HCN channels and TRIP8b could be a potential therapeutic target for treating cognitive impairment caused by chronic stress.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Cell Biology
Lulu Zhang, Xubiao Wei, Rijun Zhang, Paul E. Mozdziak, Dayong Si, Baseer Ahmad, Qiang Cheng, Yucui Tong
Summary: Immunity is a crucial defense mechanism against diseases, while immunosuppression can increase susceptibility to infections and cancer. New immunomodulatory agents, such as LTPa, have been developed to address immunosuppressive diseases and show potent effects on the immune system through binding to TLR2.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Chemistry, Medicinal
Yichen Tong, Wentao Zhu, Jian Chen, Tianzhi Wen, Fang Xu, Jiyan Pang
Summary: A series of small-molecule degraders for alpha Syn aggregates were designed and synthesized using probe molecule sery308 as a warhead. Compound 2b showed the highest degradation efficiency with high selectivity. Mechanistic exploration revealed the involvement of both proteasomal and lysosomal pathways in this degradation process. The therapeutic effects of compound 2b were demonstrated in human neuroblastoma cells and Caenorhabditis elegans, expanding the substrate spectrum of PROTAC-based degraders.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Holli-Joi Martin, Cleber C. Melo-Filho, Daniel Korn, Richard T. Eastman, Ganesha Rai, Anton Simeonov, Alexey V. Zakharov, Eugene Muratov, Alexander Tropsha
Summary: We have created a database called SMACC that includes chemogenomics data from ChEMBL for 13 emerging viruses. By solving annotation accuracy challenges, we have collected data for over 32,500 compounds with antiviral properties. This database provides valuable reference for researchers in developing novel drugs to prevent future viral outbreaks.
ANTIVIRAL RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Chao Wang, Bidong Zhang, Arne Kruger, Xiaochen Du, Lidia Visser, Alexander S. S. Domling, Carsten Wrenger, Matthew R. Groves
Summary: This study describes a series of small-molecule inhibitors targeting P. falciparum ATC with low nanomolar binding affinities, selectively binding to a previously unreported allosteric pocket, inhibiting ATC activation.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Review
Chemistry, Multidisciplinary
Amy L. Mayhugh, Preeti Yadav, Christine K. Luscombe
Summary: The translation and summary emphasizes the importance of simple and efficient methods in small molecule and polymer syntheses, highlighting the increasing interest in direct arylation polymerization (DArP) for preparing conjugated polymers. Advancements in material properties, scalability, and new monomer structures are needed in order to continue developing conjugated polymers effectively. Collaboration between small molecule and polymer-based synthetic research groups is key in informing advancements in both areas.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Multidisciplinary Sciences
Ram K. Modukuri, Zhifeng Yu, Zhi Tan, Hai Minh Ta, Melek Nihan Ucisik, Zhuang Jin, Justin L. Anglin, Kiran L. Sharma, Pranavanand Nyshadham, Feng Li, Kevin Riehle, John C. Faver, Kevin Duong, Sureshbabu Nagarajan, Nicholas Simmons, Stephen S. Palmer, Mingxing Teng, Damian W. Young, Joanna S. Yi, Choel Kim, Martin M. Matzuk
Summary: The study identified compounds with BET BD1 specificity, including CDD-787 and CDD-956, which exhibited high affinity and selectivity and demonstrated potent anti-leukemic activity in acute myeloid leukemia.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Nada H. Aljarba, Md Saquib Hasnain, Mashael Mohammed Bin-Meferij, Saad Alkahtani
Summary: The COVID-19 pandemic has caused severe or fatal respiratory tract infections worldwide. To control the infections and improve human health and socioeconomic conditions, new molecules are needed to develop drug candidates. This study identified a promising druggable candidate against the COVID main protease enzyme through virtual screening and molecular modeling.
JOURNAL OF KING SAUD UNIVERSITY SCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Victoria Vu, Magdalena M. Szewczyk, David Y. Nie, Cheryl H. Arrowsmith, Dalia Barsyte-Lovejoy
Summary: This article reviews the technologies used for evaluating the parameters and characteristics of chemical probes, focusing on cellular potency and selectivity. Additionally, it discusses the use of chemical genetic screening for phenotypic characterization of chemical probes and the significance of these data for potential therapeutic targets.
ANNUAL REVIEW OF BIOCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Gang Zhang, Feng Wang, Shan Li, Kai-Wen Cheng, Yingying Zhu, Ran Huo, Elyar Abdukirim, Guifeng Kang, Tsui-Fen Chou
Summary: RUVBL1 and RUVBL2 are highly conserved AAA ATPases that play a significant role in cancer progression. This study utilized docking-based virtual screening to identify compounds that inhibit the RUVBL1/2 complex. Seven compounds were found to have inhibitory activity in enzymatic and cellular assays. A series of pyrazolo[1,5-a]pyrimidine-3-carboxamide analogs were synthesized based on compound 15, which showed good potential for structural manipulation. Analysis of the structure-activity relationship revealed the importance of the benzyl group on R2 and the aromatic ring-substituted piperazinyl on R4 for inhibitory activity. Compound 18 exhibited the strongest inhibition and showed potential anticancer activity in multiple cell lines. Proteomic analysis identified cellular proteins dysregulated by compounds 16, 18, and 19. These findings suggest that compound 18 could serve as a starting point for structural modifications to improve potential therapeutic molecules.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Robert D. Healey, Essa M. Saied, Xiaojing Cong, Gergely Karsai, Ludovic Gabellier, Julie Saint-Paul, Elise Del Nero, Sylvain Jeannot, Marion Drapeau, Simon Fontanel, Damien Maurel, Shibom Basu, Cedric Leyrat, Jerome Golebiowski, Guillaume Bossis, Cherine Bechara, Thorsten Hornemann, Christoph Arenz, Sebastien Granier
Summary: This study presents the discovery and mechanism of action of the first drug-like inhibitors of alkaline ceramidase 3 (ACER3), as well as the characterization of enzyme:inhibitor interactions using mass spectrometry and MD simulations. The use of novel fluorescent ceramide substrates enables screening of large compound libraries, offering a new paradigm for inhibition of lipid metabolizing enzymes with non-lipidic small molecules. The findings lay the groundwork for targeting ACER3 in drug discovery efforts.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Editorial Material
Immunology
Junjie Yang, Xiaoshan Tang, Kutty Selva Nandakumar, Kui Cheng
CELLULAR & MOLECULAR IMMUNOLOGY
(2019)
Article
Chemistry, Medicinal
Zhipeng Chen, Xiaohong Cen, Junjie Yang, Zhiman Lin, Meihuan Liu, Kui Cheng
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Chemistry, Medicinal
Jingjie Bi, Wenqing Wang, Junxi Du, Kun Chen, Kui Cheng
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Review
Biochemistry & Molecular Biology
Kangmei Wen, Xiaochuan Fang, Junli Yang, Yongfang Yao, Kutty Selva Nandakumar, Mohamed Labib Salem, Kui Cheng
Summary: Flavonoids, a class of polyphenolic compounds with a basic structural unit of 2-phenylchromone, have wide potential applications in biomedicine. A review of literature on the medical use of flavonoids in the past decade has documented their pharmacological activities and mechanisms of action against various health disorders. The findings provide suggestions for further research on the biomedical applications of flavonoids.
CURRENT MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Yuqing Liang, Kutty Selva Nandakumar, Kui Cheng
BIOCHEMICAL PHARMACOLOGY
(2020)
Article
Chemistry, Medicinal
Zhipeng Chen, Lina Zhang, Junjie Yang, Lu Zheng, Fanjie Hu, Siqin Duan, Kutty Selva Nandakumar, Shuwen Liu, Hang Yin, Kui Cheng
Summary: Through chemical optimization, a highly efficient and specific human TLR2 agonist was identified, which can promote cytokine release through the MyD88 and NF-kappa B pathways, while activating immune cells to affect the apoptosis of cancer cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Yanjun Zheng, Kutty Selva Nandakumar, Kui Cheng
Summary: CAR-T cell therapy has shown efficacy in antileukemia treatment, but is hindered by severe cytokine release syndrome. Engineering small-molecule safety switches for CAR-T cells can enhance safety and therapeutic efficiency, providing pharmacological control over activities and toxicities associated with cancer immunotherapies.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Baoqu Wang, Zhenzhou Chen, Xiaohong Cen, Yuqing Liang, Liyi Tan, En Liang, Lu Zheng, Yanjun Zheng, Zhikun Zhan, Kui Cheng
Summary: This study presents the design, synthesis, and evaluation of the first LAP-activated chemiluminescent probe for tumor detection and imaging. The probe shows high selectivity and signal-to-noise ratios, and real-time imaging results demonstrate enhanced chemiluminescence at the tumor site. This probe holds potential for protein detection, disease diagnosis, and drug development.
Article
Chemistry, Analytical
Zhenzhou Chen, Baoqu Wang, Yuqing Liang, Liu Shi, Xiaohong Cen, Lu Zheng, En Liang, Lan Huang, Kui Cheng
Summary: Cysteine plays an important role in human physiological activities, but abnormal levels of cysteine are often associated with various diseases. A near-infrared fluorescence/photoacoustic dual-mode probe with high selectivity and sensitivity was developed to effectively detect cysteine. This study not only provides a new method for cysteine imaging but also offers a comprehensive and accurate tool for detecting different analytes and tumors in deep tissues, which contributes to early disease diagnosis.
ANALYTICAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Xiaohong Cen, Baoqu Wang, Yuqing Liang, Yanlin Chen, Yu Xiao, Shaohua Du, Kutty Selva Nandakumar, Hang Yin, Shuwen Liu, Kui Cheng
Summary: This study revealed the clinical relevance of TLR3 upregulation in human atherosclerosis and its contribution to the disease processes. Inhibition of TLR3 led to reduced foam cell formation and atherosclerotic burden, suggesting TLR3 as a potential novel target for atherosclerosis therapy.
ACTA PHARMACEUTICA SINICA B
(2022)
Review
Pharmacology & Pharmacy
Yinrong Wu, Zichao Yang, Kui Cheng, Huichang Bi, Jianjun Chen
Summary: Immunotherapy has revolutionized cancer treatment, with current therapies mostly based on antibodies. However, these therapies have limitations in terms of pharmacokinetics and immunogenicity. To overcome these limitations, researchers have focused on developing small molecule-based immunotherapy. This review provides an overview of the progress in small molecule-based immunomodulators for cancer therapy, including targeting PD-1/PD-L1, chemokine receptors, STING, TLR, etc. The importance of combining small molecule-based immunomodulators with therapeutic antibodies is also highlighted.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Pharmacology & Pharmacy
Junjie Yang, Yue Pan, Xiaoshan Zeng, Shuwen Liu, Zhipeng Chen, Kui Cheng
Summary: In this study, we identified Taspine as an antagonist of Toll-like receptor 2 (TLR2), which can effectively inhibit the activity of TLR2 and block the formation of the TLR2/MyD88 complex, thus reducing inflammation. We also synthesized a derivative of Taspine called SMU-Y6, which showed higher activity, better solubility, and improved drug-feasible properties. SMU-Y6 could reverse the polarization of M1 macrophages, reduce the production of inflammatory cytokines and infiltration of neutrophils, and alleviate local inflammation in mouse models.
ACTA PHARMACEUTICA SINICA B
(2023)
Article
Nanoscience & Nanotechnology
Baoqu Wang, Xiaoxue Tian, Xing-Cong Li, Kui Cheng, Min Xu
Summary: A chemiluminescent probe activated by a thiol-chromene click nucleophilic reaction was designed and prepared in this study. The probe is initially chemiluminescent but turns off and releases extremely strong chemiluminescence in the presence of thiol. Real-time imaging of mice tumor sites showed significant chemiluminescence after the probe was injected, and the chemiluminescence of osteosarcoma tissues was also significantly stronger than that in adjacent tissues. The study concludes that this chemiluminescent probe has the potential to detect thiol, diagnose cancer (especially in its early stages), and aid in the development of related cancer drugs.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Chemistry, Multidisciplinary
Yanlin Chen, Siying Zhi, Jiaxin Ou, Junbin Gao, Lu Zheng, Meixin Huang, Shaohua Du, Liu Shi, Yingfeng Tu, Kui Cheng
Summary: Immunotherapy has potential but low clinical response rate, so combined therapy is needed. This study designs cancer cell membrane-coated nanoparticles that combine PDT, TLR7 agonist, and tumor antigen to enhance therapeutic efficacy.
Article
Chemistry, Multidisciplinary
Fu-Xiaomin Liu, Weijie Chen, Lei Ma, Kui Cheng, Zhi Zhou, Wei Yi
Summary: Here, an efficient and solvent-tunable Rh(iii)-catalyzed [5+2] annulation of N-benzo[d]imidazole indolines with 2,2-difluorovinyl tosylate has been achieved, showing an unusual 1,2-regioselectivity for the construction of monofluorinated and gem-difluorinated benzodiazepines, which exhibit potent anti-tumor activity against different cancer cell lines. Overall, this work provides a powerful complement to both C-H activation chemistry and anti-tumor lead discovery.
NEW JOURNAL OF CHEMISTRY
(2023)
Review
Chemistry, Multidisciplinary
Dan He, Yawen Li, Fuwen Zhao, Yuze Lin
Summary: High trap density in organic solar cells leads to localized charge carriers and reduced carrier lifetime, limiting device efficiency. This feature article summarizes the recent advances of trap suppression by material design and device engineering.
CHEMICAL COMMUNICATIONS
(2024)
Review
Chemistry, Multidisciplinary
Olivier Monfort, Arshitha Madhusudhan, Martin Motola
Summary: This article presents the advantages of coupling photocatalysis and Fenton-based processes for environmental remediation and discusses their synergy. It critically examines the simultaneous triggering of these two processes and provides insights into research approaches. The study aims to enhance understanding of this complex process and highlight the potential integration of new catalysts in current wastewater treatment technology.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Manideepa Dhar, Chittaranjan Mishra, Avijit Das, Uttam Manna
Summary: An approach of 'polymerization of monomers in its aggregated form' has been introduced to tailor the water wettability of fibrous and porous substrates, achieving hydrophobicity to superhydrophobicity transition, as well as patterned wettability. This facile chemical method provides a durable coating with adjustable and patterned wettability for various potential applications.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Saswat Ranjan Bhoi, Chhanda Debnath, Shikha Gandhi
Summary: In this article, a novel catalytic reaction using Pd(0) and Bronsted acid is reported for the synthesis of biologically important imidazolidinone-fused N-heterocycles through redox-neutral intramolecular N-allylation of indoles and pyrroles with alkynes. This atom-economical method is applicable to a wide range of substrates and eliminates the need for leaving groups or oxidizing agents commonly used in traditional allylation reactions.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Longkun Chen, Mingshuai Zhang, Meichen Liu, Zhuoyuan Liu, Yuetong Qiu, Zhilai Zhang, Fuchao Yu, Jiuzhong Huang
Summary: In this study, an efficient Rh(III)-catalyzed selective mono- and dual-C-H bond functionalization/cyclization with iodonium ylide as the sole coupling partner was demonstrated. Fused benzodiazepine skeletons were obtained in excellent yields, providing an improved approach to dual C-H unsymmetrical functionalization.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Alice Kennett, Sven Epple, Gabriella van der Valk, Irene Georgiou, Evelyne Gout, Romain R. Vives, Angela J. Russell
Summary: This study presents the design and synthesis of sulfated disaccharide inhibitors based on IdoA(2S)-GlcNS(6S), which showed potent inhibition of Sulf-2. The results suggest that IdoA(2S)-GlcNS(6S) is the shortest fragment size required for effective inhibition of Sulfs, and a trisulfated disaccharide is identified as the minimal fragment size of heparan sulfate for effective endosulfatase inhibition.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Mauro Garbini, Andrea Brunetti, Riccardo Pedrazzani, Magda Monari, Massimo Marcaccio, Giulio Bertuzzi, Marco Bandini
Summary: The self-adaptability of galvanostatic electrolysis was found to be helpful in a multistage chemo- and diastereoselective electrochemically promoted cyclodimerization of chalcones. Through a series of reductive events, densely functionalized cyclopentanes with five contiguous stereocenters were obtained (25 examples, yields up to 95%, dr values up to >20:1). Further experimental and electrochemical investigations indicated the crucial role of dynamic kinetic resolution of the aldol intermediate in the reaction mechanism.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Dhananjay S. Nipate, Neha Meena, Prakash N. Swami, Krishnan Rangan, Anil Kumar
Summary: In this study, the synthesis of functionalized benzo[a]phenazines and indazolo[2,3-a]quinolines was achieved through Rh(III)-catalyzed oxidative annulation of 2-arylquinoxalines and 2-aryl-2H-indazoles with allyl alcohols. The method showed a wide substrate scope, excellent functional group tolerance, good to high yields of annulated products, and the capability for scaled-up synthesis. A tentative mechanism of the annulation reaction was proposed based on a preliminary mechanistic investigation.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Ruonan Zhang, Abudukadi Tudi, Xia Yang, Xuping Wang, Zhihua Yang, Shujuan Han, Shilie Pan
Summary: A new lead tellurium borate material with a unique fundamental building block [B4O10] was synthesized and found to exhibit high birefringence. The structure-property relationship was discussed using first-principles calculations.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Amresh Kumar Singh, Baishali Thakurta, Anupam Giri, Monalisa Pal
Summary: This study introduces three key concepts for the quick synthesis of large-scale high-quality 2D materials films and their utilization in device fabrication.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Reina Hagiwara, Shun Nishimura, Kosuke Okeyoshi
Summary: A copolymer-conjugated nanocatalytic system has been developed to improve electron transfer and enhance photoinduced H2 generation.
CHEMICAL COMMUNICATIONS
(2024)
