Review
Chemistry, Multidisciplinary
Yue Ma, Estrella Frutos-Beltran, Dongwei Kang, Christophe Pannecouque, Erik De Clercq, Luis Menendez-Arias, Xinyong Liu, Peng Zhan
Summary: This article discusses strategies for discovering antiviral compounds specifically designed to combat drug resistance, including targeting proteins, drug conformation, new binding sites, and host factors as potential therapeutic approaches.
CHEMICAL SOCIETY REVIEWS
(2021)
Article
Oncology
Robin Guo, Michael Offin, A. Rose Brannon, Jason Chang, Andrew Chow, Lukas Delasos, Jeffrey Girshman, Olivia Wilkins, Caroline G. McCarthy, Alex Makhnin, Christina Falcon, Kerry Scott, Yuan Tian, Fabiola Cecchi, Todd Hembrough, Deepu Alex, Ronglai Shen, Ryma Benayed, Bob T. Li, Charles M. Rudin, Mark G. Kris, Maria E. Arcila, Natasha Rekhtman, Paul Paik, Ahmet Zehir, Alexander Drilon
Summary: In MET exon 14-altered lung cancers treated with a MET TKI, the genomic mechanisms of primary resistance remain unknown, while MET expression is correlated with treatment benefit.
CLINICAL CANCER RESEARCH
(2021)
Article
Microbiology
Maria G. Nava, Felix Calderon, Elena Fernandez, Lluis Ballell, Paul Bamborough, Sumiti Vinayak
Summary: The intestinal parasite Cryptosporidium parvum is a major cause of diarrhea-associated morbidity and mortality in children, immunocompromised people, and young ruminant animals. With no effective drug available to treat cryptosporidiosis in humans and animals, there is an urgent need to identify anti-parasitic compounds and new targets for drug development.
MICROBIOLOGY SPECTRUM
(2023)
Article
Oncology
Z. Sun, C. Gu, X. Wang, A. Shang, W. Quan, J. Wu, P. Ji, Y. Yao, W. Liu, D. Li
Summary: We developed a novel bispecific antibody (BsAb) targeting both c-MET and PD-1 (PDCD1), which bridged T cells and c-MET positive tumor cells. The mechanisms and antitumor activities of the BsAb against c-MET/PD-L1 (CD274) positive colorectal cancer (CRC) were investigated in vitro and in a humanized mouse model. The BsAb exhibited potent anti-tumor activities by inhibiting c-MET signal transduction and promoting macrophage-mediated phagocytosis, with the potential to be a novel therapeutic agent for c-MET/PD-L1+ CRC patients.
INVESTIGATIONAL NEW DRUGS
(2023)
Article
Chemistry, Medicinal
SeongShick Ryu, Yunju Nam, Namkyoung Kim, Injae Shin, Eunhye Jeon, Younghoon Kim, Nam Doo Kim, Taebo Sim
Summary: In this study, we designed and synthesized several new pyridinyltriazine derivatives and identified a highly potent panFGFR inhibitor, 17a, which showed superior inhibitory and cellular activities against both wild-type and mutant FGFRs. 17a exhibited significant suppression of cancer cell proliferation by blocking FGFR signaling, inducing cell cycle arrest, and promoting apoptosis. This study provides new insights into the design of novel FGFR inhibitors targeting FGFR mutants.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Reinad R. Abu Rabah, Anusha Sebastian, Srinivasulu Vunnam, Shaista Sultan, Hamadeh Tarazi, Hanan S. Anbar, Mahmoud K. Shehata, Seyed-Omar Zaraei, Sara M. Elgendy, Salma A. Al Shamma, Hany A. Omar, Taleb H. Al-Tel, Mohammed El-Gamal
Summary: The study reports on a new series of pyrazole derivatives with potential anticancer activity. Compound 1f showed the most potent anticancer activity against various cancer cell lines, even more potent than sorafenib and SP600125. Compounds 1b, 1c, and 1h demonstrated strong anti-proliferative activity against hepatocellular carcinoma cell lines. The study also discovered two potent JNK3 inhibitors, compounds 1c and 1f, with good inhibitory effects in whole-cell assays.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Mengyang Xu, Chao Zhao, Biying Zhu, Liangyue Wang, Huihao Zhou, Daoguang Yan, Qiong Gu, Jun Xu
Summary: The study introduces a new method for discovering potent Hsp90 inhibitors by assembling fragments, providing a novel approach for finding anti-nasopharyngeal carcinoma agents. Through chemotyping analysis and click chemistry, 15 anti-Hsp90 fragments were identified, 21 compounds were synthesized, and the more potent 4f inhibitor was discovered.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Han Yao, Yuanyuan Ren, Jun Yan, Jiadai Liu, Jinhui Hu, Ming Yan, Xingshu Li
Summary: A series of tepotinib derivatives with two chiral centers were designed and synthesized as anticancer agents. Among them, the optimal compound (R, S)-12a exhibited strong antiproliferative activity against MHCC97H cell lines by inhibiting c-Met activation and the downstream AKT signaling pathway, suppressing wound closure, inducing cellular apoptosis, and arresting cell cycle at the G(1) phase in a dose-dependent fashion.
Article
Multidisciplinary Sciences
Ossama Daoui, Souad Elkhattabi, Samir Chtita, Rachida Elkhalabi, Hsaine Zgou, Adil Touimi Benjelloun
Summary: This study conducted a QSAR analysis on 48 novel compounds as anticancer agents, developing three reliable models with high correlation coefficients. Through various validation methods, drug-like properties were identified in three molecules, leading to the identification of a new potential anticancer drug candidate.
Review
Biochemistry & Molecular Biology
Marie Fernandes, Philippe Jamme, Alexis B. Cortot, Zoulika Kherrouche, David Tulasne
Summary: Although targeted therapies have extended the life expectancy of patients with druggable molecular alterations directly involved in tumor development, the emergence of acquired resistances limits their efficacy, leading to treatment failure. Recent studies have shown that activation of the MET receptor can promote resistance to various targeted therapies, highlighting MET as a key player in resistance mechanisms.
Review
Biochemistry & Molecular Biology
Fernanda Mello Tavares, Angela Cristina Gomes, Edson Mareco Assuncao, Joao Luiz Sobral de Medeiros, Marcus T. Scotti, Luciana Scotti, Hamilton Mitsugu Ishiki
Summary: This review discusses the development of novel c-KIT kinase inhibitors in the past five years using virtual screening and docking approaches. Computational techniques can identify and design new inhibitors for gastrointestinal stromal tumors, aiding cancer patients.
CURRENT MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Yan Chen, Kin Tso, Thilo J. Heckrodt, Hui Li, Rose Yen, Nan Lin, Rajinder Singh, Vanessa Taylor, Esteban S. Masuda, Gary Park, Donald G. Payan
Summary: This study investigates the structure-activity relationship of IRAK4 inhibitors and evaluates compounds 33 and 39 in vivo, demonstrating good efficacy.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Medicine, Research & Experimental
Dantong Sun, Weizheng Wu, Li Wang, Jialin Qu, Qiman Han, Huiyun Wang, Shanai Song, Ning Liu, Yongjie Wang, Helei Hou
Summary: MET fusions are rare in lung cancer patients, with an occurrence rate of 0.2% to 0.3%. In this study, intragenic MET fusions were found in 52.6% of the included patients. Crizotinib was effective in treating MET fusions, including a new type called EML4-MET fusion. This study sheds light on the rarity and therapeutic potential of MET fusions in lung cancer.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Chemistry, Medicinal
Md Ashraf-Uz-Zaman, Xin Li, Yuan Yao, Chandra Bhushan Mishra, Bala Krishna Moku, Yongcheng Song
Summary: Dengue (DENV) and Zika (ZIKV) viruses are significant human pathogens, causing about 100 million symptomatic infections annually. These infections lead to a higher incidence of serious neurological diseases, such as microcephaly and Guillain-Barre syndrome. A study identified 2,3,6-trisubstituted quinazolinone compounds as novel inhibitors of ZIKV replication. Several analogues were synthesized and tested, and compounds 22, 27, and 47 showed potent activities against ZIKV and DENV with low cytotoxicity.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Computer Science, Artificial Intelligence
Xiangcong Zeng, Yuanwen Hu, Zhi Xu, Xiaoyu Wu, Yun Xiong, Shengpeng Liu
Summary: With the progress of times, lung cancer has become increasingly prevalent and has a significant impact on human health. Tumor targeting involves targeting specific abnormal targets in tumor cells or tissues to eliminate tumor cell-specific lesions. This study developed a new c-Met inhibitor and analyzed its application in tumor therapy in combination with a multitarget tyrosine kinase inhibitor. The results showed that the combination of these inhibitors greatly promoted the development of tumor therapy.
Article
Biochemistry & Molecular Biology
Fei Ye, Xiangqian Kong, Hao Zhang, Yan Liu, Zhiyuan Shao, Jia Jin, Yi Cai, Rukang Zhang, Linjuan Li, Uang W. Zhang, Yu-Chih Liu, Chenhua Zhang, Wenbing Xie, Kunqian Yu, Hong Ding, Kehao Zhao, Shijie Chen, Hualiang Jiang, Stephen B. Baylin, Cheng Luo
ACS CHEMICAL BIOLOGY
(2018)
Article
Chemistry, Physical
Xiangqian Kong, Zhongfeng Fang, Xiaobing Bao, Zhe Wang, Shanjun Mao, Yong Wang
JOURNAL OF CATALYSIS
(2018)
Article
Oncology
Xiangqian Kong, Jie Chen, Wenbing Xie, Stephen M. Brown, Yi Cai, Kaichun Wu, Daiming Fan, Yongzhan Nie, Srinivasan Yegnasubramanian, Rochelle L. Tiedemann, Yong Tao, Ray-Whay Chiu Yen, Michael J. Topper, Cynthia A. Zahnow, Hariharan Easwaran, Scott B. Rothbart, Limin Xia, Stephen B. Baylin
Review
Chemistry, Medicinal
Fanwang Meng, Zhongjie Liang, Kehao Zhao, Cheng Luo
Summary: Modern drug design aims to discover lead compounds with attractive chemical profiles for further exploration of the intersection of chemical space and biological space, leveraging posttranslational modification (PTM) protein isoforms target space to inspire drug design. This approach seeks to extend the intersections of chemical and biological space by precisely targeting PTM protein isoforms or complexes highly relevant to biological functions, potentially increasing the tractability of compounds.
MEDICINAL RESEARCH REVIEWS
(2021)
Article
Chemistry, Medicinal
Fei Zhu, Feifei Li, Lei Deng, Fanwang Meng, Zhongjie Liang
Summary: Protein-protein interactions (PPIs) play a crucial role in biological processes, and establishing the PPI network is important for understanding biological events and disease pathogenesis. Existing machine learning models for predicting PPIs suffer from low robustness and accuracy. In this study, a new deep-learning-based framework called the SGAD model was proposed, which improves the performance of PPI network reconstruction by incorporating protein sequence descriptors, topological features, and information flow. The SGAD model achieved better predictive performance compared to other models, and its ensemble can learn more characteristics information on protein pairs for exploring the biological space of PPIs.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Biochemistry & Molecular Biology
Ennian Li, Kai Wang, Bei Zhang, Siqi Guo, Senhao Xiao, Qi Pan, Xiaowan Wang, Weiying Chen, Yunshan Wu, Hesong Xu, Xiangqian Kong, Cheng Luo, Shijie Chen, Bo Liu
Summary: A series of DNMT1 inhibitors were designed, synthesized, and evaluated as anticancer agents in this study. Among them, WK-23 showed strong inhibitory activity on human DNMT1 and had favorable pharmacokinetic properties. Therefore, WK-23 is worth developing as a DNMT1-selective therapy for the treatment of malignant tumors.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Fei Zhu, Lei Deng, Yuhao Dai, Guangyu Zhang, Fanwang Meng, Cheng Luo, Guang Hu, Zhongjie Liang
Summary: In this study, a novel deep neural network PPICT was proposed to predict PTM cross-talk by combining protein sequence-structure-dynamics information and structural information for PPI graph. The study found that cross-talk events preferentially occur among residues with high co-evolution and high potential in allosteric regulation. The PPICT method significantly improves the prediction performance and can identify PTM cross-talk between proteins at the proteome level, providing insights into cross-talk between different signal pathways introduced by PTMs.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Hao Jiang, Shijia Zu, Yu Lu, Zhongya Sun, Akejiang Adeerjiang, Qiao Guo, Huimin Zhang, Chen Dong, Qiqi Wu, Hong Ding, Daohai Du, Mingliang Wang, Chuanpeng Liu, Yong Tang, Zhongjie Liang, Cheng Luo
Summary: RhoA, a small GTPase, undergoes a conformational change from a GTP-bound state to a GDP-bound state through GTP hydrolysis, which is accelerated by GTPases activating proteins (GAPs). However, the dynamic changes in RhoA's structure during this process have been less studied, despite their importance in understanding GAP dissociation. In this study, we determined the structure of RhoA in the GDP-bound state with an outward-flipped switch II, suggesting this conformation could be an intermediate after GAP dissociation. Molecular dynamics simulations further revealed that the conformational changes in the switch regions indeed occur in RhoA and are involved in GAP dissociation and GEF recognition. Additionally, the guanine nucleotide binding pocket extends to the switch II region, providing a potential druggable cavity for RhoA. Overall, our study enhances the understanding of the dynamic properties of RhoA's switch regions and highlights their potential in future drug development.
JOURNAL OF STRUCTURAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yang-Li Zhu, Li Deng, Xin-Yan Dai, Jia-Qi Song, Yan Zhu, Ting Liu, Xiang-Qian Kong, Li-Jun Zhang, Hai-Bing Liao
Summary: A total of 17 structurally diverse clerodane diterpenoids were isolated from Tinospora crispa, including ten newly described compounds. Compound 3 exhibited anti-inflammatory activity with a ternary epoxy structure at C-3/C-4. The structures and configurations of these compounds were determined using spectroscopic data interpretation and single-crystal X-ray crystallography. Compound 3 showed inhibitory effects on neuroinflammation by modulating TLR4, Stat3, MAPK, and HO-1 signaling pathways.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Fei Zhu, Sijie Yang, Fanwang Meng, Yuxiang Zheng, Xin Ku, Cheng Luo, Guang Hu, Zhongjie Liang
Summary: This research presents two deep learning models, cDL-PAU and cDL-FuncPhos, that incorporate sequence, structure, and dynamics-based features to predict post-translational modifications (PTMs). The models achieve satisfactory prediction scores and provide insights into the molecular basis and functional landscape of PTMs.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Multidisciplinary
Mao-rong Zhu, Dao-hai Du, Jun-chi Hu, Lian-chun Li, Jing-qiu Liu, Hong Ding, Xiang-qian Kong, Hua-liang Jiang, Kai-xian Chen, Cheng Luo
ACTA PHARMACOLOGICA SINICA
(2018)
Article
Chemistry, Organic
Faiza Diaba, Gisela Trenchs
Summary: The first violet light-mediated synthesis of gamma- and delta-lactams from N-alkenyl trichloroacetamides is reported in this paper. The reactions are conducted in tetrahydrofuran or 2-methyltetrahydrofuran as the sole solvent without catalysts or additives, under non-anhydrous conditions in an air atmosphere where the solvent serves as the radical initiator.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Feroze Hussain, Sajjad Ahmed, Ashiq Hussain Padder, Qazi Naveed Ahmed
Summary: This study reports a novel and efficient one-pot synthesis method for mixed phosphorotrithioates, which does not require supplementary additives and shows broad applicability.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Hyunjin Oh, Ikyon Kim
Summary: A new 1,2,4-triazole-pyrrolo[1,2-a]pyrazine hybrid system, 6-acylpyrrolo[1,2-a][1,2,4]triazolo[5,1-c]pyrazine, was synthesized using a catalyst-free method. This method involved sequential exposure of pyrrole-2-carbonitrile-derived substrates to DMF-DMA and acyl hydrazide, resulting in the formation of acylated pyrazine and 1,2,4-triazole rings, enabling the installation of various substituents at specific positions on the core skeleton.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Ming Yan, Si-fan Wang, Yong-po Zhang, Jin-zhong Zhao, Zhuo Tang, Guang-xun Li
Summary: Here we developed an efficient photocatalytic approach for the convenient preparation of sulfinamides. The reaction allows for the gram-scale preparation of sulfinamides and the one-pot synthesis of various sulfonyl amides.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Farzaneh Bandehali-Naeini, Zahra Tanbakouchian, Noushin Farajinia-Lehi, Nicolas Mayer, Morteza Shiri, Martin Breugst
Summary: Two tandem catalytic systems were developed for the synthesis of novel 3,4-disubstituted maleimides using the same Ugi adducts. Different maleimide structures can be synthesized using either Pd or Cu catalysis.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Tanya Raghava, Anjan Chattopadhyay, Subhadeep Banerjee, Nivedita Sarkar
Summary: Amine substitution of two ortho fluorine atoms of tetrafluoroterephthalonitrile through SNAr chemistry is easily achievable. But further fluorine substitution is only possible under forcing conditions, yielding valuable fluorophores for bioimaging.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Review
Chemistry, Organic
Anju Chadha, Santosh Kumar Padhi, Selvaraj Stella, Sowmyalakshmi Venkataraman, Thangavelu Saravanan
Summary: Alcohol dehydrogenases are enzymes that use cofactors for oxidation or reduction reactions of alcohols or carbonyl compounds. They are utilized in green chemistry and have applications in the production of pharmaceuticals. Recombinant enzymes have solved the challenge of producing purified enzymes in large quantities. Engineered alcohol dehydrogenases have been used in asymmetric synthesis in industry. Various methods have been established for regenerating expensive cofactors to make the enzymatic process more efficient and economically viable.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)