Article
Biochemistry & Molecular Biology
Xu Han, Yun Long Yu, Duo Ma, Zhao Yan Zhang, Xin Hua Liu
Summary: The study synthesized 66 2-phenyl-4H-chromone derivatives with potential telomerase inhibitory activity, with compound A33 showing significant inhibition. A33 was found to arrest cell cycle at G2/M phase and induce apoptosis in a concentration-dependent manner, while also reducing dyskerin expression.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Chiara Pederiva, Davide M. Trevisan, Dimitra Peirasmaki, Shan Chen, Sharon A. Savage, Ola Larsson, Jernej Ule, Laura Baranello, Federico Agostini, Marianne Farnebo
Summary: Posttranscriptional modifications of mRNA, including pseudouridylation, play a crucial role in gene expression regulation. In this study, dyskerin, a pseudouridine synthase, was found to bind to RNA polymerase II and be responsible for pseudouridylation of thousands of mRNAs. Dyskerin-mediated pseudouridylation was shown to interfere with translation and reduction of the modification led to enhanced protein synthesis. Furthermore, dyskeratosis congenita patients with mutations in the dyskerin-encoding gene showed severe reduction in mRNA pseudouridylation.
Article
Oncology
Rafah Alnafakh, Gabriele Saretzki, Angela Midgley, James Flynn, Areege M. Kamal, Lucy Dobson, Purushothaman Natarajan, Helen Stringfellow, Pierre Martin-Hirsch, Shandya B. DeCruze, Sarah E. Coupland, Dharani K. Hapangama
Summary: The study found that dyskerin levels are significantly lower in endometrial cancer and are linked to the survival of women. Experimental results suggest that dyskerin may be a regulator of endometrial cancer cell proliferation, and may be a potential target for developing new therapies.
Article
Biochemistry & Molecular Biology
Jian Qin, Alexandre Garus, Chantal Autexier
Summary: This study reveals that mutations in the C-terminal extension (CTE) of dyskerin impair its interaction with hTR, leading to X-linked dyskeratosis congenita (X-DC) and related telomere syndromes. These mutations result in reduced binding to SHQ1 and defective binding to hTR. Furthermore, deletion of the CTE further reduces binding to hTR and disrupts the localization and interaction of dyskerin with other molecules.
HUMAN MOLECULAR GENETICS
(2023)
Article
Biochemistry & Molecular Biology
D. E. MacNeil, P. Lambert-Lanteigne, J. Qin, F. P. McManus, E. Bonneil, P. Thibault, C. Autexier
Summary: The SUMOylation of dyskerin plays a crucial role in its nuclear and subnuclear localization, which is essential for its function as both a telomerase-associated protein and an H/ACA ribonucleoprotein.
MOLECULAR AND CELLULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Neha Nagpal, Albert K. Tai, Jayakrishnan Nandakumar, Suneet Agarwal
Summary: Mutations in the DKC1 gene lead to abnormalities in scaRNA13, which can be restored by gene editing to repair mutations or inhibition of relevant enzymes; additionally, it was found that the NTE plays an important role in regulating the 3' end definition of snoRNA.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Chemistry, Medicinal
Giulia Culletta, Mario Allegra, Anna Maria Almerico, Ignazio Restivo, Marco Tutone
Summary: Telomerase plays an important role in tumor progression and is a potential target for developing cancer therapeutics. In this study, a structure-based approach was used to design potential inhibitors of telomerase. Compound 2C showed promising activity against the K-562 cell line and demonstrated better selectivity compared to a known inhibitor. Further optimization of the structure of compound 2C is warranted to obtain more active telomerase inhibitors.
Article
Chemistry, Physical
Monalisa Mahapatra, Priyanka Mohapatra, Sanjeeb Kumar Sahoo, Ajit Kumar Bishoyi, Rabindra Nath Padhy, Sudhir Kumar Paidesetty
Summary: A series of N-heteroaryl-4-(1-(2-oxo-2H-chromen-3-yl)ethylideneamino)benzenesulfonamide compounds were synthesized by condensation reactions. The structures were confirmed through various analyses and their antimicrobial and anticancer activities were evaluated. The compounds exhibited good inhibitory effects against certain microorganisms and showed potential for future therapeutic applications.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Chemistry, Physical
Nihal Inandiklioglu, Ayca Tas, Tugba Agbektas, Zuhal Tuncbilek, Kayode Yomi Raheem, Gulcihan Cinar, Yavuz Silig
Summary: This study aimed to determine the anticancer activity of the chemotherapeutic agent docetaxel in neuroblastoma cell line (SH-SY5Y) and investigate its effect on hTERT gene expression level and telomere length. The results showed that docetaxel reduced the expression level of the hTERT gene in SH-SY5Y cells and significantly shortened telomere length. Molecular docking analysis confirmed the interaction between docetaxel and the active site of telomerase.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Chemistry, Medicinal
Mykola A. Tupychak, Nataliya S. Finiuk, Rostyslav S. Stoika, Roman L. Martyak, Nazariy T. Pokhodylo
Summary: This study designed novel benzo[c]chromen-6-one linked 1,2,3-triazoles exhibiting promising in vitro anti-cancer activity and low toxicity, providing new scaffolds for the development of anti-cancer drugs.
LETTERS IN DRUG DESIGN & DISCOVERY
(2022)
Article
Oncology
Romina Armando, Maia Cabrera, Roman Vilarullo, Patricio Chinestrad, Julian Maggio, Camila Paderta, Pablo Lorenzano Menna, Daniel Gomez, Diego Mengual Gomez
Summary: This study aimed to develop novel telomerase inhibitors and identified compound R1D2-10 and its analogs as potential inhibitors of telomerase and antitumoral drugs for clinical use. Through virtual screening and in silico prediction, nine chemically different analogs with suitable ADME properties and higher docking affinity to the target were identified. Compound R1D2-10 showed an effect on inducing cellular processes related to apoptosis and senescence, suggesting its potential as a lead compound in drug development.
Article
Endocrinology & Metabolism
Huiyang Yuan, Xin Qin, Qingya Yang, Li Liu, Zhiqing Fang, Yidong Fan, Dawei Xu
Summary: In clear cell renal cell carcinoma (ccRCC) patients, high expression of DKC1 is associated with shorter disease progression-free survival (PFS) in female but not male patients. In ccRCC patients treated with Sunitinib, female patients in the DKC1-high group have lower response rates and shorter PFS. DKC1 serves as an independent female-specific predictor for survival and Sunitinib efficacy.
BIOLOGY OF SEX DIFFERENCES
(2023)
Article
Pharmacology & Pharmacy
Zuzanna Rzepka, Ewa Bebenek, Elwira Chrobak, Dorota Wrzesniok
Summary: The synthesized new 28-indole-betulin derivatives showed promising anticancer activity, particularly against MCF-7 breast cancer cells, possibly through inducing apoptosis.
Article
Chemistry, Medicinal
Lan Luo, Jing Jing Jia, Qiu Zhong, Xue Zhong, Shilong Zheng, Guangdi Wang, Ling He
Summary: The newly synthesized compound 6a has shown promising anticancer activity by inhibiting cell growth and inducing apoptosis in vitro, as well as suppressing tumor growth in vivo, indicating its potential as a future anticancer agent.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Cell Biology
Peter M. Lansdorp
Summary: Telomerase levels in most human cells are insufficient to prevent loss of telomeric DNA with each replication cycle. The resulting Hayflick limit may have allowed lifespan to increase by suppressing early tumor development but compromising cellular responses later in life. Average telomere length in leukocytes varies considerably between individuals, with females having longer telomeres than males. This difference in telomere length already exists at birth and corresponds to reported differences in average life expectancy between the sexes. The hypothesis that embryonic telomerase levels contribute to the sex differences in telomere length and lifespan requires further investigation.
Article
Biochemistry & Molecular Biology
Xing Chen, Gao-Feng Zha, Jie Quan Wang, Xin-Hua Liu
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2018)
Review
Chemistry, Medicinal
Xing Chen, Wen-Jian Tang, Jing Bo Shi, Ming Ming Liu, Xin-Hua Liu
MEDICINAL RESEARCH REVIEWS
(2020)
Article
Biochemistry & Molecular Biology
Duo Ma, Xing Chen, Xiao-Bao Shen, Liang Quan Sheng, Xin Hua Liu
BIOORGANIC CHEMISTRY
(2020)
Article
Chemistry, Medicinal
Yang Wang, Xing Chen, Yaoyao Yan, Xiaochen Zhu, Mingming Liu, Xinhua Liu
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Review
Chemistry, Medicinal
Dan Wu, Zhaoyan Zhang, Xing Chen, Yaoyao Yan, Xinhua Liu
Summary: CDK8 plays a crucial role in cancer occurrence and development, but its diverse functions and unique roles in different types of cancer have sparked interest and controversy among scientists.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Xing Chen, Yaoyao Yan, Zhaoyan Zhang, Faming Zhang, Mingming Liu, Leran Du, Haixia Zhang, Xiaobao Shen, Dahai Zhao, Jing Bo Shi, Xinhua Liu
Summary: The study details the discovery process of a potent non-peptidyl non-covalent cathepsin C inhibitor, highlighting structure-based optimization and structure-activity relationship studies. The lead compound showed strong anti-inflammatory activity in an animal model, validating the potential of non-peptidyl and non-covalent derivatives as effective cathepsin C inhibitors and prompting further drug discovery efforts.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Xiao Bao Shen, Xing Chen, Zhao Yan Zhang, Fu Fang Wu, Xin Hua Liu
Summary: Cathepsin C, an important lysosomal cysteine protease, is considered an attractive target for treating inflammatory diseases. The development of cathepsin C inhibitors will receive attention from medicinal chemists in the future.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Xing Chen, Yaoyao Yan, Juncheng Du, Xiaobao Shen, Chuanbiao He, Haitao Pan, Jun Zhu, Xinhua Liu
Summary: In this study, a novel Cat C inhibitor SF38 was identified through structure-based design and modification. SF38 exhibited strong inhibitory activity against Cat C, showed anti-inflammatory effects, and had acceptable PK properties.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Yaoyao Yan, Chen Xing, Yun Xiao, Xiaobao Shen, Zhaoyan Zhang, Chuanbiao He, Jing-Bo Shi, Mingming Liu, Xinhua Liu
Summary: This study describes the complete discovery process of a novel CDK8 inhibitor as an anti-inflammatory agent. The inhibitor was able to upregulate IL-10 levels and exhibit effective anti-inflammatory activity in an animal model of IBD.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Xing Chen, Yaoyao Yan, Xiu Cheng, Zhaoyan Zhang, Chuanbiao He, Dan Wu, Dahai Zhao, Xinhua Liu
Summary: CDK8 inhibitor CR16 enhances the transcriptional activity of AP-1 and increases IL-10 abundance, showing potential therapeutic effect in IBD treatment.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Yaoyao Yan, Chen Xing, Yun Xiao, Xiaobao Shen, Zhaoyan Zhang, Chuanbiao He, Jing-Bo Shi, Mingming Liu, Xinhua Liu
Summary: Increasing IL-10 levels through CDK8 inhibition is a promising strategy for suppressing inflammatory diseases like IBD. This study describes the discovery of a novel CDK8 inhibitor (compound85) that effectively upregulates IL-10 both in vitro and in vivo, and exhibits potent anti-inflammatory activity in an animal model of IBD.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
