Review
Oncology
Yi-Chao Zheng, Yan-Jia Guo, Bo Wang, Chong Wang, M. A. A. Mamun, Ya Gao, Hong-Min Liu
Summary: UBE2M and UBE2F are two enzymes in the NEDD8-conjugating pathway, playing important roles in posttranslational modification and potential cancer treatment targets.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Dong-Jun Fu, Ting Wang
Summary: In this study, a series of potential dual tubulin-NEDDylation inhibitors were synthesized and evaluated. Compound C11 exhibited the strongest antiproliferative activity and showed potent inhibition against tubulin and NEDDylation.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Review
Medicine, Research & Experimental
Zhang-Xu He, Wei-guang Yang, Zengyangzong Dan, Ge Gao, Qian Zhang, Hong-Min Liu, Wen Zhao, Li-Ying Ma
Summary: Protein neddylation is a crucial post-translational modification, with Cullin family proteins as its main substrates. Targeting neddylation has emerged as a promising approach for the treatment of cancer and fibrotic diseases. Several neddylation inhibitors, including MLN4924, have entered clinical trials for various cancers.
Review
Biochemistry & Molecular Biology
Shu-Yu Wang, Xu Liu, Yuan Liu, Hong-Yu Zhang, Yan-Bing Zhang, Chong Liu, Jian Song, Jin-Bo Niu, Sai-Yang Zhang
Summary: NEDDylation is a post-translational modification that transfer NEDD8 to the lysine residue of a protein, regulating biological processes and potentially inhibiting tumors. The development of NEDDylation inhibitors involves various biological detection methods.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Rongxin Li, Dan Zhang, Yueqing Han, Ke Chen, Weiran Guo, Yijun Chen, Shuzhen Wang
Summary: In this study, the researchers found that the expression of EphB1 is significantly increased in activated HSCs, accompanied by remarkable neddylation. This neddylation enhances the kinase activity of EphB1, promoting HSC proliferation, migration, and activation, and thus contributing to the development of liver fibrosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Xiaodi Du, Hongyu Song, Nengxing Shen, Ruiqi Hua, Guangyou Yang
Summary: Ubiquitin-conjugating enzymes (E2s) play a vital role in connecting ubiquitin chains to target proteins, regulating the stability and activity of substrate proteins, and participating in various biological processes. Studies have suggested their potential as therapeutic targets in cancer, leading to a need for further exploration of their molecular basis and development of effective drugs targeting E2s.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Dinesh Parshuram Satpute, Urjita Shirwadkar, Anil Kumar Tharalla, Sangita Dattatray Shinde, Gargi Nikhil Vaidya, Swarali Joshi, Priyanka Patel Vatsa, Alok Jain, Abhishek A. Singh, Rachana Garg, Amit Mandoli, Dinesh Kumar
Summary: Oral squamous cell carcinoma (OSCC) is the most common malignant epithelial neoplasm, affecting the mouth and throat, and accounting for 90% of oral cancers. The identification of a fluorinated 2-styryl 4(3H)-quinazolinone as a potential oral cancer drug candidate is reported. Initial studies show that the compound blocks the transition from G1 to S phase, leading to arrest in the G1/S phase. Subsequent RNA-seq analysis reveals that the compound activates apoptotic pathways and cell differentiation while suppressing pathways involved in cellular growth and development in CAL-27 cancer cells.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Chunlong Zhao, Yu Zhang, Jin'ge Zhang, Shunda Li, Mengyang Liu, Yinping Geng, Fengling Liu, Qipeng Chai, Hongwei Meng, Mengzhe Li, Jintao Li, Yichao Zheng, Yingjie Zhang
Summary: In this study, multitarget HDAC inhibitor 25ap was designed and synthesized. It showed potent antitumor activity by simultaneously blocking the BRD4-LIFR-JAK1-STAT3 signaling pathway and inhibiting HDAC. 25ap demonstrated an acceptable therapeutic window, stable in vitro metabolic stability, and sufficient in vivo exposure. It also exhibited strong in vivo antitumor efficacy in an MDA-MB-231 xenograft model.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Na Li, Manyi Xu, Lulu Zhang, Zhichao Lei, Cheng Chen, Tianyuan Zhang, Li Chen, Jianbo Sun
Summary: By introducing substituted imidazoles, significant improvements in antiproliferation, covalent-binding ability, and Hsp90-Cdc37 inhibition were achieved compared to CEL. Compound 9, the most potent derivative, showed higher activity in inducing apoptosis and inhibiting tumor growth in vivo. This study provides support for the development of CEL and other Michael acceptors as antitumor agents.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Jian Song, Yuan Liu, Xin-Ying Yuan, Wen-Bo Liu, Yin-Ru Li, Guang-Xi Yu, Xin-Yi Tian, Yan-Bing Zhang, Xiang-Jing Fu, Sai-Yang Zhang
Summary: The compound K3, as a NEDDylation agonist, effectively inhibits the growth of gastric cancer cells and induces cell apoptosis by promoting the degradation of c-IAP and YAP/TAZ.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Rose Ghemrawi, Mostafa Khair, Shaima Hasan, Raghad Aldulaymi, Shaikha S. AlNeyadi, Noor Atatreh, Mohammad A. Ghattas
Summary: Our study identified three SHP2 inhibitor compounds that significantly reduced proliferation and viability of breast cancer cells. These compounds showed high selectivity and promising binding modes, making them potential starting points for future anticancer drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biotechnology & Applied Microbiology
Itai Bloch, Hadar Haviv, Irena Rapoport, Elad Cohen, Rotem Shelly Ben Shushan, Nesly Dotan, Inbal Sher, Yael Hacham, Rachel Amir, Maayan Gal
Summary: Small molecule inhibitors targeting key enzymes in the biosynthesis of essential amino acids have been discovered through in vitro screening and filtering of a large molecular database. These molecules, characterized by an active phenyl-benzamide chemical group, efficiently inhibit the viability of tobacco cells and seedling growth of Arabidopsis thaliana on agar plates.
PLANT BIOTECHNOLOGY JOURNAL
(2021)
Article
Chemistry, Medicinal
Ken Nunettsu Asaba, Keiichi Okimura, Yohei Adachi, Kazuyuki Tokumaru, Yasufumi Goto, Shigeo Fujii, Akira Watanabe, Chizuka Sakai, Eri Sakurada, Kazutoshi Amikura, Takumi Aoki
Summary: We have designed, synthesized, and evaluated a series of compounds that effectively inhibit mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1). The transformation of the substructures of a starting compound led to the discovery of amidomethyl derivatives and sulfonylguanidine derivatives with potent MALT1 inhibition. Compound 37 displayed good oral bioavailability and demonstrated anti-psoriatic activity in an imiquimod-induced psoriasis mouse model upon oral administration.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Review
Pharmacology & Pharmacy
Konica Porwal, Subhashis Pal, Sudha Bhagwati, Mohd Imran Siddiqi, Naibedya Chattopadhyay
Summary: This review critically discusses the effects of PDE inhibitors in bone cells, from cellular signaling to various preclinical models evaluating bone formation mechanisms. Pentoxifylline and rolipram are the most studied inhibitors with osteogenic effects, suggesting their potential for post-menopausal osteoporosis treatment through therapeutic repurposing. These two inhibitors are treated as prototypical osteogenic PDEs to predict new chemotypes for drug design based on the structural biology of PDEs.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Bo Wang, Qiu-Hua Zhang, Xiao-Jing Li, Sai-Qi Wang, Xiao-Bing Chen, Bin Yu, Hong-Min Liu
Summary: The study reported the discovery of a novel neddylation inhibitor compound 4g, which exhibited anticancer activity against gastric cancer cells in vitro and in vivo, showing effective tumor growth inhibition without obvious toxicity. The cinnamyl piperidine derivatives could potentially serve as new lead compounds for developing highly effective neddylation inhibitors for gastric cancer therapy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)