Article
Biochemistry & Molecular Biology
Jinghong Xian, Faqian Bu, Yuxi Wang, Fangyi Long, Zhixiong Zhang, Chengyong Wu, Yiran Tao, Ting Wang, Guan Wang
Summary: IC261, an ATP-competitive inhibitor of serine/threonine-specific casein kinase 1 (CK1), has shown inhibitory activity on microtubule polymerization. This study provides a high-resolution crystal structure of tubulin and IC261 complex, revealing the intermolecular interaction and structure-activity relationship. Comparison with tubulin-colchicine complex and molecular docking studies led to the discovery of potential new microtubule inhibitors based on IC261.
Article
Chemistry, Medicinal
Xiang-Yu Yan, Jia-Fu Leng, Ting-Ting Chen, Yong-Jun Zhao, Ling-Yi Kong, Yong Yin
Summary: A series of novel diphenylamine derivatives were synthesized and evaluated for their anti-proliferative activities against human cancer cell lines. Among them, compound 5f exhibited promising anti-proliferative activity against HT29 cells and showed inhibitory effects on cancer cell migration, colony formation, and angiogenesis. Further studies revealed that compound 5f inhibited tubulin polymerization, arrested HT29 cell cycle, induced cell apoptosis, and inhibited tumor growth in animal models. The compound also demonstrated good pharmacokinetic properties. These findings suggest that compound 5f has potential as an antitumor candidate and warrants further investigation.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Shanbo Yang, Chao Wang, Lingyu Shi, Jing Chang, Yujing Zhang, Jingsen Meng, Wenjing Liu, Jun Zeng, Renshuai Zhang, Yingchun Shao, Dongming Xing
Summary: A set of novel diarylpyridines as anti-tubulin agents were designed and synthesised, among which compound 10t showed remarkable antiproliferative activities and disrupted the cellular microtubule structure, arrested cell cycle and induced apoptosis.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Laura Gallego-Yerga, Rodrigo Ochoa, Isaias Lans, Carlos Pena-Varas, Melissa Alegria-Arcos, Pilar Cossio, David Ramirez, Rafael Pelaez
Summary: Tubulin is a validated target for various drugs, but there is a lack of anticancer drugs targeting the colchicine site. By utilizing X-ray structures of tubulin in complex with ligands, researchers designed a novel tubulin modulator by combining scaffolds that best fit the ensemble pharmacophore-representation.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Bulian Deng, Zhiqiang Sun, Yuxi Wang, Ruiyao Mai, Zichao Yang, Yichang Ren, Jin Liu, Junli Huang, Zeli Ma, Ting Chen, Canjun Zeng, Jianjun Chen
Summary: This study designed a series of novel imidazo[1,2-a]pyrazine derivatives as potential tubulin inhibitors through structural optimization and ring fusion strategy. Among them, compound TB-25 exhibited the strongest inhibitory effects against HCT-116 cells. It could effectively inhibit tubulin polymerization and destroy the dynamic equilibrium of microtubules in cells, induce G2/M phase cell cycle arrest and apoptosis, and suppress cell migration.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Yichang Ren, Yong Ruan, Binbin Cheng, Ling Li, Jin Liu, Yuyu Fang, Jianjun Chen
Summary: Compound 3b, designed as a tubulin inhibitor targeting the colchicine binding site, showed high antiproliferative activity against HepG-2 cells, with the ability to suppress microtubule polymerization, disrupt dynamics, inhibit cancer cell migration, induce cell cycle arrest and apoptosis. Docking studies indicated its potential as a novel tubulin inhibitor deserving further investigation.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Gang Li, Jia-Qiang Wu, Xiaojia Cai, Wen Guan, Zhijun Zeng, Yanghui Ou, Xiaoyun Wu, Jiayu Li, Xiangxiang Fang, Jinling Liu, Yali Zhang, Huamin Wang, Canqiang Yin, Hongliang Yao
Summary: A series of diaryl heterocyclic analogues were synthesized as tubulin polymerization inhibitors. Compound 6y exhibited the highest antiproliferative activity against HCT-116 colon cancer cells and effectively inhibited tubulin polymerization in vitro. It also showed high metabolic stability on human liver microsomes and suppressed tumor growth in a HCT-116 mouse colon model without toxicity. These results suggest that 6y represents a new class of tubulin inhibitors worthy of further investigation.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Shengtao Xu, Yijun Sun, Peng Wang, Yuchen Tan, Lei Shi, Jian Chen
Summary: Angiogenesis is an important process in tumor development and progression. In this study, a series of novel dihydro-1H-indene derivatives were designed and evaluated as tubulin polymerisation inhibitors, showing anti-angiogenic activities. Compound 12d was identified as the most potent derivative, with strong antiproliferative activity against multiple cancer cell lines. It bound to the colchicine site on tubulin, inhibited tubulin polymerisation, and effectively prevented tumor growth, proliferation, and angiogenesis in vivo. These findings suggest that compound 12d is a promising tubulin polymerisation inhibitor for further research.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Xiang-Jing Fu, Jiao Huang, Na Li, Yun-He Liu, Qiu-Ge Liu, Shuo Yuan, Yan Xu, Yi-Fan Chen, Yu-Xuan Zhao, Jian Song, Sai-Yang Zhang, Yi-Ru Bai
Summary: In this study, we designed and synthesized 33 novel N-benzylaryl cinnamide derivatives and evaluated their in vitro anti-tumor activities. Among them, compound 15e (MY-1076) showed significant inhibitory activity against multiple tumor cells by inhibiting tubulin polymerization and promoting YAP degradation.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Buduma Komuraiah, Yichang Ren, Mingming Xue, Binbin Cheng, Jin Liu, Yao Liu, Jianjun Chen
Summary: Compound 4d, a novel tubulin inhibitor, displayed high antiproliferative activity, inhibited tubulin polymerization, induced cell cycle arrest, and inhibited cancer cell migration in a dose-dependent manner. These results suggest that compound 4d represents a new class of promising tubulin inhibitors for further investigation.
CHEMICAL BIOLOGY & DRUG DESIGN
(2021)
Article
Pharmacology & Pharmacy
Laura Gallego-Yerga, Valentin Cena, Rafael Pelaez
Summary: The use of benzothiazole scaffold in designing colchicine site ligands has resulted in a new family of ligands with high water solubility. These ligands exhibit antiproliferative activity against various cancer cell lines, with high selectivity towards cancer cells. The most potent derivatives show nanomolar range IC50 values, even in difficult-to-treat glioblastoma cells. Flow cytometry experiments and confocal microscopy observations confirm the cell cycle arrest and apoptotic cell death induced by these ligands, which are attributed to their ability to disrupt microtubule network. Docking studies further support the interaction of the ligands at the colchicine binding site. These results validate the effective strategy of developing potent anticancer colchicine ligands with improved water solubility.
Article
Oncology
Shanshan Deng, Souvik Banerjee, Hao Chen, Satyanarayana Pochampally, Yuxi Wang, Mi-Kyung Yun, Stephen W. White, Keyur Parmar, Bernd Meibohm, Kelli L. Hartman, Zhongzhi Wu, Duane D. Miller, Wei Li
Summary: This study reports a novel inhibitor, SB226, which shows great promise for cancer therapy. Through extensive preclinical studies and in vitro/in vivo experiments, it was confirmed that SB226 has high affinity for tubulin dimers, exhibits anti-proliferative activities, inhibits tumor growth, induces apoptosis, and shows no obvious toxicity.
Article
Biochemistry & Molecular Biology
Mohamed Hagras, Moshira A. El Deeb, Heba S. A. Elzahabi, Eslam B. Elkaeed, Ahmed B. M. Mehany, Ibrahim H. Eissa
Summary: Newly synthesized quinoline derivatives exhibited superior cytotoxic activities and inhibitory effects against tubulin polymerisation in human cancer cell lines, potentially serving as promising anticancer agents.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Runlai Liu, Shuai Zhang, Mingxin Huang, Zhenpeng Guo, Long Li, Mi Li, Lan Wu, Qi Guan, Weige Zhang
Summary: The newly designed compound 6d showed significant antiproliferative activity against MCF-7 cancer cells, inhibiting cancer cell growth and migration through multiple pathways.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Rajan Sharma Bhattarai, Virender Kumar, Svetlana Romanova, Jitender Bariwal, Hao Chen, Shanshan Deng, Vijaya R. Bhatt, Tatiana Bronich, Wei Li, Ram Mahato
Summary: CH-3-8, a novel microtubule polymerization inhibitor, showed significant anti-proliferative effects on pancreatic cancer cells and induced apoptosis. Conjugating CH-3-8 with dodecanol and encapsulating it in nanoparticles resulted in high drug loading and potential for enhanced therapeutic outcomes against pancreatic cancer.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Biochemistry & Molecular Biology
Yuanyuan Li, Jiazhen Yang, Lu Niu, Daojun Hu, Huijuan Li, Lijuan Chen, Yamei Yu, Qiang Chen
Article
Chemistry, Medicinal
Zeping Zuo, Xiaocong Liu, Xinying Qian, Ting Zeng, Na Sang, Huan Liu, Yue Zhou, Lei Tao, Xia Zhou, Na Su, Yamei Yu, Qiang Chen, Youfu Luo, Yinglan Zhao
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Cell Biology
Rie Ayukawa, Seigo Iwata, Hiroshi Imai, Shinji Kamimura, Masahito Hayashi, Kien Xuan Ngo, Itsushi Minoura, Seiichi Uchimura, Tsukasa Makino, Mikako Shirouzu, Hideki Shigematsu, Ken Sekimoto, Benoit Gigant, Etsuko Muto
Summary: This study demonstrates that the formation of straight oligomers of critical size is essential for nucleation of microtubules. Both GDP and GTP tubulin form single-stranded oligomers with different curvature distributions, and the proportion of straight oligomers can accelerate nucleation. The results suggest that cellular factors involved in nucleation promote it via stabilization of straight oligomers.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Chengyong Wu, Dongmei Tang, Jie Cheng, Daojun Hu, Zejing Yang, Xue Ma, Haihuai He, Shaohua Yao, Tian-Min Fu, Yamei Yu, Qiang Chen
Summary: This study presents the biochemical reconstitution of the Synechocystis sp. PCC6803 type I-D adaptation system and provides insights into the competition between Cas4 and Cas2 for interaction with Cas1. Cas4 and Cas1 form a stable complex in the absence of prespacer, while the Cas1-prespacer complex develops a higher binding affinity toward Cas2 for ternary complex formation. Together, these findings reveal a two-step sequential assembly mechanism for the type I-D adaptation module of Synechocystis.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Paloma F. Varela, Melanie Chenon, Christophe Velours, Kristen J. Verhey, Julie Menetrey, Benoit Gigant
Summary: Motile kinesins are motor proteins that move along microtubules by hydrolyzing ATP. This study provides structural insights into the nucleotide cycle of OSM-3, demonstrating a shared ATPase mechanism similar to that of Eg5 in the kinesin superfamily.
Article
Biochemistry & Molecular Biology
Dongmei Tang, Huijuan Li, Chengyong Wu, Tingting Jia, Haihuai He, Shaohua Yao, Yamei Yu, Qiang Chen
Summary: This study revealed a distinct structure of the Cas1-Cas2 complex in Pyrococcus furiosus, showing a unique binding mode for pre-spacers. The structural and mutagenesis results led to a model confirming the pre-spacer preference and providing a potential explanation for longer spacer acquisition in P. furiosus. The research showcases the diversity of the CRISPR adaptation module.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Pharmacology & Pharmacy
Hong Tan, Huali Wang, Jinhu Ma, Hui Deng, Qinghua He, Qiang Chen, Qinglian Zhang
Summary: This study found that lactate dehydrogenase C (LDHC) is significantly expressed in lung cancer tissues, and overexpression of LDHC can promote tumor growth, while knock-down of LDHC can inhibit cancer cell proliferation. The crystal structure of human LDHC4 was determined and found to have a distinct conformation compared to LDHA4 and lactate dehydrogenase B4 (LDHB4). Additionally, (ethylamino) (oxo)acetic acid was shown to selectively inhibit LDHC4. These findings suggest that LDHC4 could be a potential target for anticancer drug discovery.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Chemistry, Multidisciplinary
Andreas Stein, Persefoni Hilken Nee Thomopoulou, Corazon Frias, Sina M. Hopff, Paloma Varela, Nicola Wilke, Arul Mariappan, Jorg-Martin Neudoerfl, Alexey Yu Fedorov, Jay Gopalakrishnan, Benoit Gigant, Aram Prokop, Hans-Gunther Schmalz
Summary: The synthesis and investigation of PT-100, a potential anticancer drug, were reported. PT-100 exhibited high antiproliferative and apoptosis-inducing effects, especially in multidrug-resistant cancer cell lines, and showed synergistic effects with vincristine in certain cell lines.
Article
Biochemistry & Molecular Biology
Lifang Xie, Yun Hu, Li Li, Lurong Jiang, Yaoge Jiao, Yanhong Wang, Lifang Zhou, Rui Tao, Junyan Qu, Qiang Chen, Shaohua Yao
Summary: The recognition of PAM is crucial for the CRISPR/Cas9 system, and this study demonstrates that the non-PI domain fragment of xCas9 protein can expand PAM recognition and improve editing efficiency. This finding can also be applied to other Cas9 variants.
Article
Multidisciplinary Sciences
Valerie Campanacci, Agathe Urvoas, Liza Ammar Khodja, Magali Aumont-Nicaise, Magali Noiray, Sylvie Lachkar, Patrick A. Curmi, Philippe Minard, Benoit Gigant
Summary: The study demonstrates the binding of CPAP's PN2-3 domain with tubulin and the similarity in binding mode with fungal and bacterial inhibitors. This finding uncovers the characteristic features of cellular partners binding to this site and highlights the structural convergence of CPAP with small-molecule inhibitors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Rui Tao, Yanhong Wang, Yaoge Jiao, Yun Hu, Li Li, Lurong Jiang, Lifang Zhou, Junyan Qu, Qiang Chen, Shaohua Yao
Summary: Prime editors with Cas9-nickase and reverse transcriptase enable targeted precise editing of small DNA pieces, expanding the editing scope and improving efficiency and accuracy.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Jie Cheng, Yamei Yu, Xingyu Wang, Xi Zheng, Ting Liu, Daojun Hu, Yongfeng Jin, Ying Lai, Tian-Min Fu, Qiang Chen
Summary: To form a functional neural circuit, neurons develop specific molecular features to distinguish self from non-self. Both the invertebrate Dscam family and the vertebrate Pcdh family play a role in determining synaptic specificity. A recently identified shortened Dscam (sDscam) in Chelicerata exhibits characteristics of both Dscam and Pcdh isoforms, representing an evolutionary transition. This study reveals the molecular details of sDscam self-recognition through trans and cis interactions, proposing a molecular zipper model for sDscam assemblies and cell-cell recognition.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Weizhi Chen, Rui Liu, Yamei Yu, Dongqing Wei, Qiang Chen, Qin Xu
Summary: This study uncovers the molecular mechanisms of cancer-causing mutations in DCLK1 by analyzing its crystal structure and performing molecular dynamics simulations. The disruption of the assembly of the autoinhibitory domain leads to exposure of a key residue in the kinase domain. The researchers conducted a screening process and evaluated the binding affinity of potential inhibitors to DCLK1.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Dongmei Tang, Tingting Jia, Yongbo Luo, Biqin Mou, Jie Cheng, Shiqian Qi, Shaohua Yao, Zhaoming Su, Yamei Yu, Qiang Chen
Summary: In the spacer acquisition stage of CRISPR-Cas immunity, spacer orientation and protospacer adjacent motif (PAM) removal are important for functional spacer integration. Cas4 is involved in processing the prespacer and determining spacer orientation. Host 3'-5' DnaQ family exonucleases have been found to play a similar role in Cas4-lacking systems, but the details of their functions are still unclear.
Article
Biotechnology & Applied Microbiology
Yanhong Wang, Lifang Zhou, Rui Tao, Nan Liu, Jie Long, Fengming Qin, Wenling Tang, Yang Yang, Qiang Chen, Shaohua Yao