Article
Chemistry, Medicinal
Yiying Wei, Xinxin Xu, Minchuan Jiang, Yongxing Wang, Yang Zhou, Zhen Wang, Zhang Zhang, Fengtao Zhou, Ke Ding
Summary: A new selective GSPT1 degrader was developed, which could effectively degrade GSPT1 and showed good selectivity in the global proteomic profiling study. The compound also displayed good antiproliferative activities and induced cell cycle arrest and apoptosis in U937 cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Oncology
Liguo Wang, Zhouli Yang, Guangchen Li, Yongbo Liu, Chao Ai, Yu Rao
Summary: This article summarizes the latest developments in CDK and cyclin protein degraders, covering their selectivity, application, validation, and the current state of development for CDK members lacking degraders. It provides a comprehensive overview for researchers in this field.
FRONTIERS OF MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Akshay D. Takwale, Eun Yeong Kim, Yerin Jang, Dong Ho Lee, Seulgi Kim, Yuri Choi, Jin Hwan Kim, Da Yeon Lee, Yeongrin Kim, So Myoung Lee, Heung Kyoung Lee, Hye Jin Nam, Joo-Youn Lee, Jin Hwa Cho, Jeong Hee Moon, Ga Seul Lee, Jeong-Hoon Kim, Pilho Kim, Chi Hoon Park, Jong Yeon Hwang
Summary: This study investigated the structure-activity relationship of novel GSPT1 degraders using the benzotriazinone scaffold. Compound 34f demonstrated strong anti-proliferative effects and effectively induced GSPT1 degradation, suggesting its potential as an anti-tumor agent.
BIOORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Andrew D. Huber, Yongtao Li, Wenwei Lin, Annalise N. Galbraith, Ashutosh Mishra, Shaina N. Porter, Jing Wu, Rebecca R. Florke Gee, Wei Zhuang, Shondra M. Pruett-Miller, Junmin Peng, Taosheng Chen
Summary: This study describes the discovery of a molecule, SJPYT-195, which can reduce the protein level of PXR by acting as a molecular glue degrader of GSPT1, a translation termination factor. The findings provide insights into the chemical determinants of drug-induced GSPT1 degradation and also present assays and cell models for the discovery of PXR degraders.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Medicinal
Wenzhi Ji, Eric S. Wang, Theresa D. Manz, Jie Jiang, Katherine A. Donovan, Xianmixinuer Abulaiti, Eric S. Fischer, Lewis C. Cantley, Tinghu Zhang, Nathanael S. Gray
Summary: Phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks), consisting of three members (alpha, beta, and gamma) in mammals, have attracted attention as potential therapeutic targets due to their involvement in regulating various vital cellular signaling pathways. Among them, PI5P4K gamma shows distinct expression patterns and has been implicated in cancer and neurodegenerative diseases. A novel PI5P4K gamma degrader, JWZ-1-80, has been developed and characterized, exhibiting potent degradation activity and selective targeting towards PI5P4K gamma via the ubiquitin-proteasome system, which makes it a valuable tool compound for further investigations on the biological functions of PI5P4K gamma.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Oncology
Sandeep Rana, Jayapal Reddy Mallareddy, Sarbjit Singh, Lidia Boghean, Amarnath Natarajan
Summary: Cyclin-dependent kinases (CDKs) are important therapeutic targets in cancer treatment, but lack of selectivity and dose-limiting toxicities are challenges, alternative strategies like PROTACs and molecular glues have emerged. These new modalities utilize protein degradation machinery to modulate target protein function.
Article
Chemistry, Medicinal
Shulei Zhu, Jieyu Liu, Donghuai Xiao, Peipei Wang, Jingkun Ma, Xiaobei Hu, Jingfeng Fu, Yubo Zhou, Jia Li, Wei Lu
Summary: This study reports a novel Wee1 degrader based on PROTAC technology, which effectively degrades cellular Wee1 protein and has potential applications in cancer therapy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Alice Ghidini, Antoine Clery, Francois Halloy, Frederic H. T. Allain, Jonathan Hall
Summary: RNA-PROTACs represent a novel approach for targeting RBPs by using small RNA mimics to induce proteasomal degradation, potentially holding promise for applications in cancer cells.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Tim Keuler, Beate Koenig, Nico Bueckreiss, Fabian B. Kraft, Philipp Koenig, Linda Schaeker-Huebner, Christian Steinebach, Gerd Bendas, Michael Guetschow, Finn K. Hansen
Summary: The development of a new class of selective HDAC6 degraders based on a difluoromethyl-1,3,4-oxadiazole (DFMO) warhead as ZBG is reported, providing a promising approach to treat HDAC6-driven diseases.
CHEMICAL COMMUNICATIONS
(2022)
Review
Chemistry, Medicinal
Bin Yu, Zekun Du, Yuming Zhang, Zhiyu Li, Jinlei Bian
Summary: Proteolysis-targeting chimeras are a new modality of chemical tools and potential therapeutics that induce protein degradation, with CDK-targeting degraders showing advantages in potency, selectivity, and drug resistance compared to traditional CDK inhibitors. The discovery of molecule glues has further promoted the development of CDK degraders, with a focus on discussing the structural characteristics and design of these degraders.
FUTURE MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Chao Wang, Cangxin Zheng, Han Wang, Liangren Zhang, Zhenming Liu, Ping Xu
Summary: Protein degradation technology has made significant progress since its first report in 2001. Various degradation technologies based on PROTAC have been developed for different targets, expanding the possibilities for treating cancer, neurodegenerative diseases, and viral diseases. Over 15 targeted degraders have entered clinical trials to date.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Chemistry, Medicinal
Chao Wang, Han Wang, Cangxin Zheng, Zhenming Liu, Xiaozuo Gao, Fengrong Xu, Yan Niu, Liangren Zhang, Ping Xu
Summary: MEK1/2 are key components of the ERK pathway involved in regulating cellular processes. Targeting MEK is important for cancer therapy, and PROTAC technology can potentially overcome resistance to MEK inhibitors by inducing MEK degradation.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Xiaqiu Qiu, Yuanqing Li, Bin Yu, Jie Ren, Huidan Huang, Min Wang, Hong Ding, Zhiyu Li, Jubo Wang, Jinlei Bian
Summary: CDK9 inhibitor BAY-1143572 converted into PROTACs leads to degradation of CDK9 in acute myeloid leukemia cells, with the most potent molecule B03 showing enhanced antiproliferative activity. This enhanced activity is mediated by increased kinase inhibitory activity and apoptosis induction levels. B03 can also induce CDK9 degradation in vivo, indicating its potential as a therapeutic strategy in acute myeloid leukemia.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Chemistry, Medicinal
Siyu Chen, Jingliang Cui, Haiyan Chen, Bo Yu, Sihui Long
Summary: Targeted protein degradation is a key strategy in current cancer therapy, and Proteolysis targeting chimera (PROTAC) is a popular branch that induces target protein degradation by activating the ubiquitin-proteasome system. In addition to intracellular proteins, membrane proteins have also been reported to be degraded, and other effective membrane protein degradation strategies have emerged.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Maohua Cai, Furong Ma, Can Hu, Haobin Li, Fei Cao, Yulong Li, Jinyun Dong, Jiang-Jiang Qin
Summary: Ferroptosis, a newly discovered form of regulated cell death driven by iron-dependent lipid peroxidation, has been proposed as an effective treatment strategy for cancer by inactivating glutathione peroxidase 4 (GPX4). However, the development of GPX4 inhibitors is limited. This study focuses on the design, synthesis, and evaluation of GPX4-targeting proteolysis targeting chimeras (PROTACs), with one of the synthesized PROTACs, CRBN-based PROTAC GDC-11, showing promising potential in inducing ferroptosis in cancer cells. Docking and theoretical calculations provide insights into the moderate degrading effect of these PROTACs. This work lays the foundation for further studies and synthesis of GPX4-targeting degraders.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Bo Wang, Jacob Ingemar Olsen, Bo W. Laursen, Jens Christian Navarro Poulsen, Mikael Bols
Article
Chemistry, Applied
Zhongfu Wang, Yang Liu, Yujiao Sun, Qing Mou, Bo Wang, Ying Zhang, Linjuan Huang
Article
Plant Sciences
Xiao Rui Zhang, Wen Xia Zhou, Yong Xiang Zhang, Chun Hui Qi, Huanga Yan, Zhong Fu Wang, Bo Wang
JOURNAL OF ETHNOPHARMACOLOGY
(2011)
Article
Multidisciplinary Sciences
Bo Wang, Elena Zaborova, Samuel Guieu, Marta Petrillo, Maxime Guitet, Yves Bleriot, Mickael Menand, Yongmin Zhang, Matthieu Sollogoub
NATURE COMMUNICATIONS
(2014)
Article
Chemistry, Multidisciplinary
Stephanie A. Blaszczyk, Guozhi Xiao, Peng Wen, Hua Hao, Jessica Wu, Bo Wang, Francisco Carattino, Ziyuan Li, Daniel A. Glazier, Bethany J. McCarty, Peng Liu, Weiping Tang
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2019)
Article
Chemistry, Medicinal
Bo Wang, Suzhen Wu, Jin Liu, Ka Yang, Haibo Xie, Weiping Tang
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Chemistry, Organic
Bo Wang, Sidsel Ammitzboll Bogh, Jens Christian Navarro Poulsen, Bo W. Laursen, Mikael Bols
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2020)
Article
Chemistry, Medicinal
Line Malue Langhorn, Bo Wang, Morten Meldal, Mikael Bols
Summary: Three different cyclodextrin acids were attached to amino PEGA resin as amides and studied for their host-guest binding with ANS. The binding characteristics and dissociation constants were determined, showing selective inhibition by specific guest molecules for certain cyclodextrin acids.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Medicinal
Haibo Xie, Chunrong Li, Hua Tang, Ira Tandon, Junzhuo Liao, Brett L. Roberts, Yu Zhao, Weiping Tang
Summary: Substituted achiral phenyl dihydrouracil (PDHU) was developed as a novel class of CRBN ligands for PROTACs. Some substituted PDHUs showed comparable binding affinity to lenalidomide. Structural modeling provided insights into the molecular interactions between PDHU ligands and CRBN. PDHUs also demonstrated greater stability than lenalidomide. Finally, potent BRD4 degraders were developed using trisubstituted PDHUs.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Multidisciplinary
Yu Chen, Ira Tandon, William Heelan, Yixin Wang, Weiping Tang, Quanyin Hu
Summary: Proteolysis Targeting Chimeras (PROTACs) have the potential to revolutionize the healthcare industry by degrading target proteins. However, inadequate delivery to the target site is one of the main challenges for PROTACs. The integration of PROTACs and delivery systems is being explored to enhance their in vivo performance.
CHEMICAL SOCIETY REVIEWS
(2022)
Article
Biochemistry & Molecular Biology
Ka Yang, Yu Zhao, Xueqing Nie, Hao Wu, Bo Wang, Chelsi M. Almodovar-Rivera, Haibo Xie, Weiping Tang
CELL CHEMICAL BIOLOGY
(2020)
Meeting Abstract
Hematology
Therese Vu, Wenjuan Liao, Weiwei Yang, Ira Tandon, Patricia Ernst
EXPERIMENTAL HEMATOLOGY
(2019)
Article
Chemistry, Multidisciplinary
Bo Wang, Mikael Bols
CHEMISTRY-A EUROPEAN JOURNAL
(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)