Article
Biochemistry & Molecular Biology
Huanxian Wu, Lishun Zhang, Boyu Chen, Baofang Ou, Jiahuan Xu, Nannan Tian, Danni Yang, Yangcheng Ai, Qianqing Chen, Dongling Quan, Tingting Zhang, Lin Lv, Yuanxin Tian, Jiajie Zhang, Shaoyu Wu
Summary: B13 is an effective drug that inhibits the proliferation and metastasis of colorectal cancer cells, inducing cell cycle arrest and apoptosis. It has low toxicity and superior antitumor activity compared to Vismodegib. By binding to Smo protein, B13 inhibits the expression of downstream gene Gli1 and its localization in the nucleus, overcoming resistance caused by SmoD473H mutations.
BIOORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Junwan Fan, Haowen Li, Lun Kuang, Zichen Zhao, Wenyan He, Chen Liu, Yongjun Wang, Steven Y. Cheng, Wei Chen
Summary: A new Smoothened inhibitor, 0025A, has been discovered in this study, which effectively targets the Hedgehog signaling pathway and inhibits cancer cell activity. Additionally, it can suppress hair growth in mice.
CELL AND BIOSCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Jian Yi Chai, Vaisnevee Sugumar, Mohammed Abdullah Alshawsh, Won Fen Wong, Aditya Arya, Pei Pei Chong, Chung Yeng Looi
Summary: The Hedgehog (Hh)-glioma-associated oncogene homolog (GLI) signaling pathway is highly conserved in mammals and plays crucial roles in cancer initiation and progression. GLI transcription factors are regulated by both SMO-dependent and SMO-independent mechanisms, with dysregulation leading to tumorigenesis in various cancers. Understanding the complex interplay between GLI and signaling elements could inspire new therapeutic breakthroughs for Hh-GLI-dependent cancers.
Review
Pharmacology & Pharmacy
Karmani Shah, Shivangi Panchal, Bhumika Patel
Summary: Porcupine, a member of the Wnt family, modulates cellular responses by palmitoylating Wnt proteins, showing potential in treating various cancers. While no Porcupine inhibitors have been commercialized yet, several molecules have progressed to Phase I clinical trials.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Neurosciences
Alice Del Giovane, Mariagiovanna Russo, Linda Tirou, Helene Faure, Martial Ruat, Sonia Balestri, Carola Sposato, Francesco Basoli, Alberto Rainer, Abdelmoumen Kassoussi, Elisabeth Traiffort, Antonella Ragnini-Wilson
Summary: This study shows that non-canonical signaling pathways can promote the maturation and regeneration of myelin cells, suggesting a potential role in the treatment of demyelinating diseases.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Liu-Ya Tang, Marie Spezia, Ting Chen, Jee-Hye Shin, Feng Wang, Frank Stappenbeck, Andres M. Lebensohn, Farhad Parhami, Ying E. Zhang
Summary: The study revealed that oxysterols Oxy186 and Oxy210 can inhibit proliferation of NSCLC cells, with Oxy186 exhibiting potent inhibition of tumor growth. The mechanism of action involves inhibiting the WNT/beta-catenin signaling pathway.
CELL AND BIOSCIENCE
(2022)
Review
Cell Biology
Piotr Cierpikowski, Anna Leszczyszyn, Julia Bar
Summary: Head and neck squamous cell carcinoma (HNSCC) is a significant global malignancy with limited treatment options. The Hedgehog (HH) signaling pathway, which is involved in tissue development and maintenance, may play a crucial role in HNSCC and cancer stem cell regulation. Recent research suggests that targeting the HH pathway could be a promising approach for personalized therapy for HNSCC. This review provides an overview of the current understanding and potential implications of the HH pathway in HNSCC.
Article
Ophthalmology
Jing-Yu Qu, Yu-Ting Xiao, Ying-Ying Zhang, Hua-Tao Xie, Ming-Chang Zhang
Summary: The Hedgehog signaling pathway plays an important role in regulating proliferation and differentiation of RMGECs, potentially offering a therapeutic approach for treating meibomian gland dysfunction (MGD).
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Review
Cell Biology
Mia C. Borlongan, Hongbin Wang
Summary: Tumorigenic cancer stem cells (CSCs) are a subset of cells within tumors that have distinct genetic and phenotypic profiles and signaling pathways compared to other tumor cells. Targeting the unique self-renewal and differentiation properties of CSCs could revolutionize cancer therapy. Understanding the signaling mechanisms of CSCs will improve our knowledge of cancer pathology and treatment.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Cell Biology
Jianhang Jia, Jin Jiang
Summary: This review focuses on the essential role of Smoothened (Smo) protein in Hedgehog (Hh) signal transduction, as well as the regulatory mechanisms of Smo endocytosis and degradation in both insects and vertebrates. It discusses how Hh inhibits Smo ubiquitination and promotes Smo surface/ciliary accumulation through ubiquitin-specific protease 8 (USP8) in Drosophila, and also highlights the induction of sumoylation by Hh in regulating Smo trafficking and abundance in both Drosophila and mammalian cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Cell Biology
Jie Zhang, Zulong Liu, Jianhang Jia
Summary: SMO, a seven-transmembrane protein critical for hedgehog signal transduction, is regulated by multiple post-translational modifications and small molecules to maintain its activity balance and impact developmental defects and cancer initiation.
Article
Cell Biology
Weidong Zhang, Niu Wang, Tongtong Zhang, Meng Wang, Wei Ge, Xin Wang
Summary: The study unveils the promoting effect of melatonin on cashmere development through regulating Wnt signaling and stem cell pluripotency. Melatonin exposure induces changes in cell factors and gene expression, affecting cell proliferation and stem cell potential.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Chemistry, Medicinal
Li Chen, Maolun Liu, Han Yang, Shan Ren, Qiang Sun, Hui Zhao, Tianqi Ming, Shun Tang, Qiu Tao, Sha Zeng, Xianli Meng, Haibo Xu
Summary: It has been discovered that ursolic acid (UA), a compound found in medicinal herbs, has potent effects against colorectal cancer (CRC) by inhibiting non-canonical Hedgehog signaling. This study investigated the influence of UA on non-canonical Hedgehog signaling in CRC, and found that UA inhibited cell proliferation, induced apoptosis, and down-regulated signaling proteins in CRC cells. Furthermore, UA also improved symptoms, inhibited tumor growth, and induced apoptosis in a CRC xenograft model.
PHYTOTHERAPY RESEARCH
(2022)
Review
Cell Biology
Florian Hermans, Lara Hemeryck, Ivo Lambrichts, Annelies Bronckaers, Hugo Vankelecom
Summary: Tooth development relies on interactions between dental epithelium and mesenchyme, regulated by molecular pathways including Wnt, BMP, FGF, and Shh. These signaling modules intertwine during tooth development, outlining specific cell populations' development pathways.Recent studies have uncovered crucial Wnt-Shh interactions during odontogenesis, showing conservation in developing ectodermal appendages.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Junwan Fan, Zichen Zhao, Ru Liu, Haowen Li, Wenyan He, Jianping Wu, Yongjun Wang, Wei Chen
Summary: Our study found that the new Smoothened inhibitor TT22 can effectively block the translocation of β-arrestin2-GFP to Smoothened in neurons, reduce the accumulation of Smoothened on primary cilia, and inhibit the expression of downstream Gli transcription factor. In addition, TT22 also inhibits abnormal seizure-like activity in neurons.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Immunology
Sudan He, Xiaodong Wang
Review
Biochemistry & Molecular Biology
Fang Zhu, Wei Zhang, Tao Yang, Su-dan He
JOURNAL OF ZHEJIANG UNIVERSITY-SCIENCE B
(2019)
Article
Cell Biology
Jue Hou, Jie Ju, Zili Zhang, Cong Zhao, Zhanhui Li, Jiyue Zheng, Tian Sheng, Hongjian Zhang, Linkun Hu, Xiaoliang Yu, Wei Zhang, Yangxin Li, Meng Wu, Haikuo Ma, Xiaohu Zhang, Sudan He
CELL DEATH & DISEASE
(2019)
Article
Chemistry, Medicinal
Fang Zhu, Yujie Wang, Qian Du, Wenxiang Ge, Zhanhui Li, Xu Wang, Chunyan Fu, Lusong Luo, Sheng Tian, Haikuo Ma, Jiyue Zheng, Yi Zhang, Xiaotian Sun, Sudan He, Xiaohu Zhang
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Microbiology
Qiang Huang, Jue Hou, Peng Yang, Jun Yan, Xiaoliang Yu, Ying Zhuo, Sudan He, Feng Xu
Article
Biochemistry & Molecular Biology
Chengkui Yang, Qiao Ran, Yifei Zhou, Shan Liu, Cong Zhao, Xiaoliang Yu, Fang Zhu, Yuting Ji, Qian Du, Tao Yang, Wei Zhang, Sudan He
Article
Chemistry, Medicinal
Yu Lin, Zhanhui Li, Haikuo Ma, Yujie Wang, Xu Wang, Shiwei Song, Li Zhao, Shuwei Wu, Sheng Tian, Chunyan Fu, Lusong Luo, Fang Zhu, Sudan He, Jiyue Zheng, Xiaohu Zhang
Article
Cell Biology
Cong Zhao, Yifei Zhou, Qiao Ran, Ying Yao, Haoran Zhang, Jie Ju, Tao Yang, Wei Zhang, Xiaoliang Yu, Sudan He
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Yu Lin, Zhanhui Li, Chen Xu, Kaijiang Xia, Shuwei Wu, Yongjin Hao, Qing Yang, Haikuo Ma, Jiyue Zheng, Lusong Luo, Fang Zhu, Sudan He, Xiaohu Zhang
BIOORGANIC CHEMISTRY
(2020)
Article
Cell Biology
Kaijiang Xia, Fang Zhu, Chengkui Yang, Shuwei Wu, Yu Lin, Haikuo, Xiaoliang Yu, Cong Zhao, Yuting Ji, Wenxiang Ge, Jingrui Wang, Yayun Du, Wei Zhang, Tao Yang, Xiaohu Zhang, Sudan He
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2020)
Article
Chemistry, Medicinal
Shuwei Wu, Chen Xu, Kaijiang Xia, Yu Lin, Sheng Tian, Haikuo Ma, Yuting Ji, Fang Zhu, Sudan He, Xiaohu Zhang
Summary: Novel RIPK3 inhibitors were designed, synthesized, and evaluated, with lead compound 38 showing potent activity and good selectivity and safety profiles. Compound 38 efficiently blocked cell death and demonstrated promising therapeutic effects in a mouse model.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Zhanhui Li, Yongjin Hao, Chengkui Yang, Qing Yang, Shuwei Wu, Haikuo Ma, Sheng Tian, Haohao Lu, Jingrui Wang, Tao Yang, Sudan He, Xiaohu Zhang
Summary: This study reports a series of potent RIPK1 inhibitors, with compound 70 being highly active and stable in blocking necroptosis in inflammatory signaling and cell death. Compound 70 exhibits excellent properties and activity in both in vitro and in vivo experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Xiaoyan Dou, Xiaoliang Yu, Shujing Du, Yu Han, Liang Li, Haoran Zhang, Ying Yao, Yayun Du, Xinhui Wang, Jingjing Li, Tao Yang, Wei Zhang, Chengkui Yang, Feng Ma, Sudan He
Summary: MiR-324-5p negatively regulates necroptosis by targeting MLKL expression, and its downregulation by interferons facilitates the activation of necroptosis for host antiviral defense.
Article
Hematology
Xiaoliang Yu, Haikuo Ma, Bohan Li, Yuting Ji, Yayun Du, Siying Liu, Zhanhui Li, Yongjin Hao, Sheng Tian, Cong Zhao, Qian Du, Zhongqin Jin, Xueming Zhu, Yuanyuan Tian, Xin Chen, Xue Sun, Chengkui Yang, Fang Zhu, Jie Ju, Yunjing Zheng, Wei Zhang, Jingrui Wang, Tao Yang, Xinhui Wang, Jingjing Li, Xiangping Xu, Shujing Du, Haohao Lu, Feng Ma, Haibing Zhang, Yi Zhang, Xiaohu Zhang, Shaoyan Hu, Sudan He
Summary: Intestinal epithelial cells (IECs) require receptor-interacting protein kinase-3 (RIPK3) to drive gastrointestinal (GI) tract and systemic graft-versus-host disease (GVHD) after stem cell transplantation. The RIPK1/RIPK3 cascade in IECs triggers the production of T-cell-recruiting chemokines and MHC class II molecules, leading to a feed-forward inflammatory cascade. Targeting RIPK1/RIPK3 in IECs presents a potential strategy for treating GVHD and GI tract inflammation.
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)