Review
Biochemistry & Molecular Biology
Antal H. Kovacs, Dong Zhao, Jinqiang Hou
Summary: This paper presents a comprehensive review of the preclinical and clinical candidates of Aurora B inhibitors as potential anticancer drugs. The recent advances in the field of Aurora B inhibitor development will be highlighted, and the binding interactions between Aurora B and inhibitors based on crystal structures will be presented and discussed to provide insights for the future design of more selective Aurora B inhibitors.
Review
Biochemistry & Molecular Biology
Ruijuan Du, Chuntian Huang, Kangdong Liu, Xiang Li, Zigang Dong
Summary: AURKA is overexpressed in cancers and regulates substrate functions through phosphorylation, participating in various classic oncogenic pathways.
Review
Chemistry, Physical
Priya, Shalini Jaswal, Ghanshyam Das Gupta, Sant Kumar Verma
Summary: Aurora kinase family plays a critical role in cell division and the cell cycle, and overexpression of AURKA and AURKB has been linked to the development of various carcinomas. The synthesis and development of Aurora Kinase inhibitors offer new opportunities for anticancer therapy.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Chemistry, Medicinal
Bin Zhang, Chengchen Zhu, Albert S. C. Chan, Gui Lu
Summary: This study reports the discovery of irreversible inhibitors for Aurora A kinase, which play critical roles in cell cycle regulation and mitotic spindle assembly. One of the inhibitors, 11c, showed selective inhibition against normal and cancer cells, as well as Aurora A and B kinases. The study suggests that 11c may be a promising drug candidate for the treatment of triple negative breast cancer.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Oncology
Alessio Stefani, Geny Piro, Francesco Schietroma, Alessandro Strusi, Emanuele Vita, Simone Fiorani, Diletta Barone, Federico Monaca, Ileana Sparagna, Giustina Valente, Miriam Grazia Ferrara, Ettore D'Argento, Mariantonietta Di Salvatore, Carmine Carbone, Giampaolo Tortora, Emilio Bria
Summary: Lung cancer is categorized into NSCLC and SCLC, with the former having actionable targets for advanced treatment and the latter lacking oncogene-addiction concept. Aurora kinases (AURKs) play a crucial role in cell cycle progression and their overexpression is a common protumorigenic pathway in various cancer types, influencing drug resistance mechanisms.
FRONTIERS IN ONCOLOGY
(2022)
Article
Chemistry, Physical
Dong Zhao, Antal H. Kovacs, Michael Campbell, Wely Floriano, Jinqiang Hou
Summary: In this study, the selective binding mechanism of Barasertib, a ligand with high selectivity for Aurora kinase B over A, was investigated through molecular dynamics simulations and binding free energy analyses. The results showed that the hinge residue Arg159 in Aurora kinase B played a crucial role in Barasertib binding, and the binding interactions at the hydrophobic back pocket were important for the selectivity. The insights into the structural determinants of subtype selectivity will contribute to the development of selective Aurora kinase B inhibitors for cancer therapy.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Review
Oncology
Azaj Ahmed, Anas Shamsi, Taj Mohammad, Gulam Mustafa Hasan, Asimul Islam, Md. Imtaiyaz Hassan
Summary: This article provides a detailed analysis of Aurora B kinase, emphasizing its importance in the cell cycle, particularly its regulation during mitosis and its impact on cancer progression. The study also highlights the use of small-molecule inhibitors in controlling tumor proliferation and provides insights into their mechanisms of action.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Eman M. E. Dokla, Amal Kamal Abdel-Aziz, Sandra N. Milik, Amr H. Mahmoud, Mona Kamal Saadeldin, Martin J. McPhillie, Saverio Minucci, Khaled A. M. Abouzid
Summary: Aurora B is a crucial cell cycle regulator with potential therapeutic implications in cancer treatment. Through structure-based design, the derivatives 6e and 8a showed optimal activity against Aurora B and MDA-MB-468 cells, inducing cell cycle arrest, apoptosis, and reducing clonogenic potential. These compounds exhibited better safety profiles compared to multikinase inhibitors and represent promising candidates for further development targeting breast cancer.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Mohammad Jalalirad, Tufia C. Haddad, Jeffrey L. Salisbury, Derek Radisky, Minzhi Zhang, Mark Schroeder, Ann Tuma, Eduard Leof, Jodi M. Carter, Amy C. Degnim, Judy C. Boughey, Jann Sarkaria, Jia Yu, Liewei Wang, Minetta C. Liu, Luca Zammataro, Lorenzo Malatino, Evanthia Galanis, James N. Ingle, Matthew P. Goetz, Antonino B. D'Assoro
Summary: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer, with progression linked to the enrichment of breast tumor-initiating cells (BTICs) and chemoresistance. The study revealed that AURKA kinase plays a critical role in mediating TGF-beta-induced TNBC plasticity, chemoresistance, and tumor progression.
Review
Chemistry, Medicinal
Naga Rajiv Lakkaniga, Zhengyu Wang, Yao Xiao, Anupreet Kharbanda, Li Lan, Hong-yu Li
Summary: Aurora Kinase B, as a therapeutic target for cancer treatment, has been studied for more than two decades. Inhibitors of Aurora Kinase B show promising biological results in vitro and in vivo experiments. Although no approved inhibitors for clinical use are available due to associated side effects, they exhibit excellent synergy with other treatment methods, making them a potential adjuvant therapy for difficult-to-treat cancers.
MEDICINAL RESEARCH REVIEWS
(2023)
Article
Oncology
Manuela Mancini, Cecilia Monaldi, Sara De Santis, Cristina Papayannidis, Michela Rondoni, Chiara Sartor, Samantha Bruno, Livio Pagano, Marianna Criscuolo, Roberta Zanotti, Massimiliano Bonifacio, Patrizia Tosi, Michel Arock, Peter Valent, Michele Cavo, Simona Soverini
Summary: Proteasome inhibitors can suppress cell growth and induce apoptosis in neoplastic mast cells by promoting SETD2/H3K36Me3 re-expression. Aurora kinase A and MDM2 are implicated in SETD2 loss of function in AdvSM. Targeting Aurora A or proteasome inhibitors may have therapeutic potential in AdvSM treatment.
BIOMARKER RESEARCH
(2023)
Article
Oncology
Tufia C. Haddad, Vera J. Suman, Antonino B. D'Assoro, Jodi M. Carter, Karthik V. Giridhar, Brendan P. McMenomy, Katelyn Santo, Erica L. Mayer, Meghan S. Karuturi, Aki Morikawa, P. Kelly Marcom, Claudine J. Isaacs, Sun Young Oh, Amy S. Clark, Ingrid A. Mayer, Khandan Keyomarsi, Timothy J. Hobday, Prema P. Peethambaram, Ciara C. O'Sullivan, Roberto A. Leon-Ferre, Minetta C. Liu, James N. Ingle, Matthew P. Goetz
Summary: This randomized clinical trial found that adding fulvestrant to treatment with alisertib did not increase objective tumor response rates (ORRs) or progression-free survival (PFS) in endocrine-resistant metastatic breast cancer (MBC).
Article
Biochemical Research Methods
Lauren J. Tomlinson, Matthew Batchelor, Joscelyn Sarsby, Dominic P. Byrne, Philip J. Brownridge, Richard Bayliss, Patrick A. Eyers, Claire E. Eyers
Summary: Protein kinase inhibitors are effective in treating diseases driven by aberrant kinase signaling and can help understand the cellular roles of kinase signaling complexes. This study characterizes the conformational changes and stability of protein kinase Aurora A (Aur A) caused by binding of the physiological activator TPX2 or small molecule inhibitors using gas-phase ion-mobility mass spectrometry (IM-MS). The results show that inhibitor binding induces more compact configurations of Aur A, leading to the stabilization of active Aur A.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2022)
Review
Biochemistry & Molecular Biology
Dalila Boi, Elisabetta Rubini, Sara Breccia, Giulia Guarguaglini, Alessandro Paiardini
Summary: Myc transcription factors play crucial roles in many cellular processes and its overexpression is frequently associated with cancer. The interplay between Myc and kinases is essential for tumor cell proliferation, with kinase inhibitors showing potential for cancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
P. M. Gurubasavaraja Swamy, Nahid Abbas, Prasad Sanjay Dhiwar, Ekta Singh, Abhishek Ghara, Arka Das
Summary: In this study, a 3D QSAR pharmacophore model was generated using substituted pyrimidine class of Aurora-A kinase inhibitors, revealing the crucial role of molecular features in inhibitory activity. Five potential compounds were identified through screening and docking, demonstrating their distinctive ability to inhibit Aurora-A kinase.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Richard Kuan-Lin Lee, Tian-Neng Li, Sui-Yuan Chang, Tai-Ling Chao, Chun-Hsien Kuo, Max Yu-Chen Pan, Yu-Ting Chiou, Kuan-Ju Liao, Yi Yang, Yi-Hsuan Wu, Chen-Hao Huang, Hsueh-Fen Juan, Hsing-Pang Hsieh, Lily Hui-Ching Wang
Summary: This study developed a new method to detect the molecular interaction between the receptor-binding domain (RBD) of SARS-CoV-2 and the ACE2 receptor, and identified two drugs, Etravirine and Dolutegravir, as effective entry inhibitors against SARS-CoV-2. These drugs showed similar neutralizing activities against different variants of the virus.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Chemistry, Multidisciplinary
Chih-Ming Chen, Hsing-Pang Hsieh
Summary: The Diels-Alder adducts of masked ortho-benzoquinone (MOB) exhibit high regio- and stereoselectivity and can be formed under mild conditions. MOB has various functional groups, is easily accessible, and can be used for complex structure construction through chemical transformations. Therefore, MOB is considered an important intermediate for total synthesis of natural products.
JOURNAL OF THE CHINESE CHEMICAL SOCIETY
(2022)
Article
Chemistry, Medicinal
Gollagani Vijaya Bhavani, Sree Karani Kondapuram, Aifa Fathima Shamsudeen, Mohane Selvaraj Coumar, Joseph Selvin, Tharanikkarasu Kannan
Summary: Novel isoniazid-based pyridinium salts were designed, synthesized, and tested for their antimycobacterial activities, and 4k, 4l, and 7d showed exceptional activities. In vitro and in silico studies suggested that 4k is a potentially promising lead compound for the development of antitubercular candidates.
DRUG DEVELOPMENT RESEARCH
(2023)
Article
Chemistry, Medicinal
Mu-Chun Li, Mohane Selvaraj Coumar, Shu-Yu Lin, Yih-Shyan Lin, Guan-Lin Huang, Chun-Hwa Chen, Tzu-Wen Lien, Yi-Wen Wu, Yen-Ting Chen, Ching-Ping Chen, Yu-Chen Huang, Kai-Chia Yeh, Chen-Ming Yang, Bikashita Kalita, Shiow-Lin Pan, Tsu-An Hsu, Teng-Kuang Yeh, Chiung-Tong Chen, Hsing-Pang Hsieh
Summary: The development of orally bioavailable, furanopyrimidine-based double-mutant (L858R/T790M) EGFR inhibitors is discussed. The selectivity for mutant EGFR was achieved by replacing the (S)-2-phenylglycinol moiety with either an ethanol or an alkyl substituent. The optimized lead compound 52 displayed selective inhibition of cancer cells overexpressing EGFRL858R/T790M and showed in vivo antitumor effects in mouse xenograft models.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Ying-Ting Hsu, Shen-Ren Chen, Yung-Chiao Chang, Hsiao-Fu Chang, Teng-Kuang Yeh, Jian-Ying Chuang, Horace H. Loh, Hsing-Pang Hsieh, Shau-Hua Ueng, Shiu-Hwa Yeh
Summary: The demand for a non-addictive analgesic medication is increasing due to clinical misuse. Compound 14 is a dual agonist of the mu opioid receptor (MOR) and nociceptin-orphanin FQ opioid peptide (NOP) receptor, providing pain relief at very small doses and reducing unwanted side effects. Evaluating its effects in wild type and humanized mice can help develop a safer prescription analgesic drug.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Environmental Sciences
Paola Brinez-Gallego, Dennis Guilherme da Costa Silva, Ana Paula Horn, Mariana Appel Hort
Summary: This study aimed to investigate the effects of curcumin on L-DOPA induced toxicity. The results suggest that curcumin improves motor impairment induced by L-DOPA and reduces levels of reactive oxygen species and lipid peroxidation products in zebrafish larvae.
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES
(2023)
Article
Chemistry, Organic
Chih-Ming Chen, Sheng-Kuo Lin, Chi-Tien Hsieh, Julakanti Satyanarayana Reddy, Yi Ning Teoh, Mu-Jeng Cheng, Hsing-Pang Hsieh
Summary: An acyl radical reaction of bicyclo[2.2.2]octenone is described, which can yield rearranged or cyclized isotwistane products. The influence of ring strain on the reaction was demonstrated. DFT calculations showed that the reaction is under thermodynamic control and proceeds via a 5-exo-trig cyclization intermediate, which can undergo either hydrogen-atom transfer to give a cyclized product or rearrangement via a twistane intermediate to give a rearranged product.
Article
Chemistry, Medicinal
Mu -Chun Li, Mohane Selvaraj Coumar, Shu-Yu Lin, Yih-Shyan Lin, Guan-Lin Huang, Chun-Hwa Chen, Tzu-Wen Lien, Yi-Wen Wu, Yen-Ting Chen, Ching-Ping Chen, Yu-Chen Huang, Kai-Chia Yeh, Chen -Ming Yang, Bikashita Kalita, Shiow-Lin Pan, Tsu-An Hsu, Teng-Kuang Yeh, Chiung-Tong Chen, Hsing-Pang Hsieh
Summary: This article describes the development of orally bioavailable, furanopyrimidine-based double-mutant (L858R/T790M) EGFR inhibitors. Selectivity for mutant EGFR was achieved by replacing the (S)-2-phenylglycinol moiety of compound 12 with either an ethanol or an alkyl substituent. The lead compound 52 showed 8-fold selectively inhibition of H1975 (EGFR(L858R/T790M) overexpressing) cancer cells and displayed in vivo antitumor effects in two mouse xenograft models with TGI = 74.9% and 97.5% after oral administration (F = 27%).
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Pownraj Brindangnanam, Krishnan Ashokkumar, Sriraghavan Kamaraj, Mohane Selvaraj Coumar
Summary: Antimicrobial resistance (AMR) is a global medical crisis, causing millions of deaths annually. Acinetobacter baumannii, a dangerous nosocomial pathogen, has developed resistance to multiple antibiotics. Blocking drug efflux transporters (DETs) can enhance the efficacy of antibiotics, and a compound called KSA5 has been identified to successfully block antibiotic efflux in A. baumannii. KSA5 has optimal physicochemical and ADME properties, making it a promising candidate for overcoming antimicrobial resistance when combined with antibiotics.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Review
Cell Biology
Monika Kumari, Ruei-Min Lu, Mu-Chun Li, Jhih-Liang Huang, Fu-Fei Hsu, Shih-Han Ko, Feng-Yi Ke, Shih-Chieh Su, Kang-Hao Liang, Joyce Pei-Yi Yuan, Hsiao-Ling Chiang, Cheng-Pu Sun, I-Jung Lee, Wen-Shan Li, Hsing-Pang Hsieh, Mi-Hua Tao, Han-Chung Wu
Summary: The COVID-19 pandemic continues to be a global health crisis, and while vaccines and therapeutics have been developed, challenges remain in addressing the effectiveness against new variants and supporting clinical trials.
JOURNAL OF BIOMEDICAL SCIENCE
(2022)
Article
Cell Biology
Jai-Shin Liu, Wei-Kai Fang, Shan-Min Yang, Meng-Chen Wu, Tsan-Jan Chen, Chih-Ming Chen, Tung-Yueh Lin, Kai-Lun Liu, Chien-Ming Wu, Yun-Ching Chen, Chih-Pin Chuu, Ling-Yu Wang, Hsing-Pang Hsieh, Hsing-Jien Kung, Wen-Ching Wang
Summary: Myricetin, identified as a potent alpha-ketoglutarate-type inhibitor, blocks the demethylation activity by KDM4s and reduces the proliferation of both androgen-dependent and androgen-independent CRPC cells. A synergistic cytotoxic effect is observed for the combination of myricetin and enzalutamide on CRPC cells. PLGA-encapsulated myricetin in combination with enzalutamide shows significant antitumor activity in a CRPC xenograft model, suggesting its potential effectiveness for CRPC.
JOURNAL OF BIOMEDICAL SCIENCE
(2022)
Meeting Abstract
Oncology
Chun H. Cheung, Tzu Y. Lin, Sailu Sarvagalla, Mohane S. Coumar, Siao M. Cheng, Euphemia Leung
Article
Cell Biology
You-Liang Lai, Kai-Hung Wang, Hsing-Pang Hsieh, Wan-Ching Yen
Summary: DBPR114 showed activity against HCC tumor cell proliferation in vitro regardless of p53 alteration status and tumor grade. It induced growth inhibition in HCC cells through apoptosis induction, cell cycle arrest, and polyploidy formation. DBPR114 also exhibited anti-angiogenic effects and significantly inhibited tumor growth in multiple HCC tumor xenograft models.
JOURNAL OF BIOMEDICAL SCIENCE
(2022)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
