Article
Chemistry, Multidisciplinary
Yi-fan Chen, Run-zhi Liu, Wen-wen Ying, Yue-ning Yang, Sen-feng Xiang, Xue-jing Shao, Ji Cao, Yan-qi Zhang, Bo Yang, Qiao-jun He, Mei-dan Ying
Summary: Neddylation is a posttranslational protein modification commonly found in cancers. This study focused on the role of UBC12, one of the key enzymes in the neddylation pathway, in cancer progression. The researchers found that UBC12 is overexpressed in most cancer types and its overexpression is associated with lower survival rates in cancer patients. Additionally, they discovered that arctigenin, a natural product, is able to inhibit UBC12 enzyme activity and suppress the malignant behavior of cancer cells. These findings suggest that UBC12 could be a potential therapeutic target for cancer treatment, and arctigenin could be a promising compound for inhibiting neddylation-overactivated cancers.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Oncology
Duc-Vinh Pham, Nirmala Tilija Pun, Pil-Hoon Park
Summary: Leptin induces growth of breast cancer cells through reprogramming of lipid metabolism and activation of autophagy, with crucial roles played by SREBP-1 induction and fatty acid synthase induction. Autophagy mediates the metabolic effects of leptin on cancer cell-specific metabolism, highlighting its pivotal contribution to tumor growth.
MOLECULAR ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Xiaohong Xia, Tumei Hu, Xiaoyue He, Yuan Liu, Cuifu Yu, Weiyao Kong, Yuning Liao, Daolin Tang, Jinbao Liu, Hongbiao Huang
Summary: This study reveals that neddylation of HER2 is a novel post-translational modification that regulates its expression and oncogenic activity in human breast cancer. The inhibition of neddylation synergizes with trastuzumab to suppress the growth of HER2 positive breast cancer.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Xiaohong Xia, Tumei Hu, Xiaoyue He, Yuan Liu, Cuifu Yu, Weiyao Kong, Yuning Liao, Daolin Tang, Jinbao Liu, Hongbiao Huang
Summary: This study reveals that neddylation of HER2 controls its expression and oncogenic activity in human breast cancer. NEDD8 and NAE1, critical components in the neddylation pathway, are found to be positively correlated with HER2 expression. HER2 interacts directly with NEDD8 and NAE1, and neddylation inhibition leads to decreased HER2 protein expression.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Article
Cell Biology
Maria J. Gonzalez-Rellan, Uxia Fernandez, Tamara Parracho, Eva Novoa, Marcos F. Fondevila, Natalia da Silva Lima, Lucia Ramos, Amaia Rodriguez, Marina Serrano-Macia, Gonzalo Perez-Mejias, Pilar Chantada-Vazquez, Cristina Riobello, Christelle Veyrat-Durebex, Sulay Tovar, Roberto Coppari, Ashwin Woodhoo, Markus Schwaninger, Vincent Prevot, Teresa C. Delgado, Miguel Lopez, Antonio Diaz-Quintana, Carlos Dieguez, Diana Guallar, Gema Fruhbeck, Irene Diaz-Moreno, Susana B. Bravo, Maria L. Martinez-Chantar, Ruben Nogueiras
Summary: Neddylation is a post-translational modification mechanism that regulates metabolism in the liver of mice and is associated with liver pathology in patients with type 2 diabetes. Fasting or calorie restriction leads to neddylation of phosphoenolpyruvate carboxykinase 1 (PCK1), affecting its metabolic activity.
Article
Oncology
Duc-Vinh Pham, Pil-Hoon Park
Summary: This study elucidates the multifaceted role of adiponectin in tumor fatty acid metabolic reprogramming and provides evidence for the connection between its metabolic actions and suppression of breast cancer.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Pan Hu, Peiyi Zhou, Tieyun Sun, Dingkang Liu, Jun Yin, Lubin Liu
Summary: This study highlights the significance of targeting lipid synthesis pathways in the treatment of triple-negative breast cancer (TNBC). The therapeutic protein PAK has been shown to inhibit TNBC progression by downregulating genes involved in fatty acid synthesis. The findings suggest a new strategy for regulating lipid synthesis and its therapeutic importance in TNBC.
BREAST CANCER RESEARCH
(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
Cell Biology
Yanyu Jiang, Lihui Li, Yan Li, Guangwei Liu, Robert M. Hoffman, Lijun Jia
Summary: The neddylation pathway regulates the function, migration, survival, and polarization of macrophages, highlighting its implications for cancer therapy.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Li Tang, Da Wei, Xinyu Xu, Dongping Mo, Daofu Cheng, Feng Yan
Summary: This study demonstrates that CYP1B1-AS1 inhibits protein neddylation to affect breast cancer cell proliferation, providing a new strategy for the treatment of breast cancer by targeting lncRNA-mediated neddylation modification.
BREAST CANCER RESEARCH AND TREATMENT
(2023)
Article
Oncology
Jesus Fuentes-Antras, Ana Lucia Alcaraz-Sanabria, Esther Cabanas Morafraile, Maria del Mar Noblejas-Lopez, Eva Maria Galan-Moya, Mariona Baliu-Pique, Igor Lopez-Cade, Vanesa Garcia-Barberan, Pedro Perez-Segura, Aranzazu Manzano, Atanasio Pandiella, Balazs Gyorffy, Alberto Ocana
Summary: Breast cancer is a major cause of mortality worldwide and remains incurable in advanced stages. Dysregulation of post-translational machinery, particularly ubiquitination and SUMOylation, has been found to influence tumorigenesis and drug resistance, with potential implications for therapeutic intervention. Identifying and targeting these genomic alterations in ubiquitination enzymes could lead to novel drug development strategies for breast cancer.
Review
Oncology
Qiushi Zhao, Xingyu Lin, Guan Wang
Summary: SREBP-1, a crucial transcription factor, is involved in the metabolic reprogramming of various cancers and can serve as a biomarker for prognosis or drug efficacy in cancer patients. This review discusses the structure, activation, and key upstream signaling pathways of SREBP-1, as well as its potential targets and therapeutic approaches in cancer treatment.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Tung-Yu Tiong, Pei-Wei Weng, Chun-Hua Wang, Syahru Agung Setiawan, Vijesh Kumar Yadav, Narpati Wesa Pikatan, Iat-Hang Fong, Chi-Tai Yeh, Chia-Hung Hsu, Kuang-Tai Kuo
Summary: This study investigated the role of SREBP-1 in NSCLC biology, progression, and therapeutic response and found that the targeting of SREBP-1/hsa-miR-497 signaling axis could be a potentially effective anticancer therapeutic strategy for NSCLC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Yumi Kim, Wona Jee, Eun-Jin An, Hyun Min Ko, Ji Hoon Jung, Yun-Cheol Na, Hyeung-Jin Jang
Summary: Timosaponin A3 (TA3) was found to inhibit pancreatic cancer growth through the regulation of sterol regulatory element-binding protein-1 (SREBP-1), providing a potential novel approach for the prevention and treatment of pancreatic cancer.
Review
Cell Biology
Wenbin Gai, Zhiqiang Peng, Cui Hua Liu, Lingqiang Zhang, Hong Jiang
Summary: NEDD8 is a key protein involved in the progression of tumors, with its inhibitor MLN4924 showing promise in treating cancer. Inhibiting the neddylation pathway can effectively halt the development of tumors.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Chemistry, Medicinal
Hong-Rae Kim, Ravichandra Tagirasa, Euna Yoo
Summary: Cells of the immune system use proteases to regulate functions and immune responses, with dysregulated activities linked to disorders. Compounds that modify protease active sites covalently are emerging as important drugs, serving as both chemical probes and approved agents for pharmaceutical development.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Organic
Young Eum Hyun, Hong-Rae Kim, Lak Shin Jeong
Summary: Asymmetric synthesis was used to synthesize conformationally locked south (S) and north (N) analogues of sugars, with different synthetic strategies employed to obtain the two conformations.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Hyejin Lee, Dnyandev B. Jarhad, Ahrim Lee, Choongho Lee, Lak Shin Jeong
Summary: Researchers designed and synthesized potential anti-HCV agents 2'-C-methyl-4'-selenoribavirin and -acadesine, characterized them, and effectively synthesized 2'-C-methyl 4'-selenoacadesine through a purine-ring opening/degradation procedure involving N3-C2 bond cleavage.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Karishma K. Mashelkar, Woong Sub Byun, Hyejin Ko, Kisu Sung, Sushil K. Tripathi, Seungchan An, Yun A. Yum, Jee Youn Kwon, Minjae Kim, Gibae Kim, Eun-Ji Kwon, Hyuk Woo Lee, Minsoo Noh, Sang Kook Lee, Lak Shin Jeong
Summary: The study introduces a novel 4'-thionucleoside template as a multi-kinase inhibitor with potent anticancer activity, exhibiting marked inhibition of TRKA, CK1 delta, and DYRK1A/1B kinases. The development of such inhibitors that occupy the ribose pocket, along with the hinge and hydrophobic region, may pave the way for the advancement of anticancer drugs.
Article
Biochemistry & Molecular Biology
Sujin Park, Yujin Ahn, Yongchan Kim, Eun Joo Roh, Yoonji Lee, Chaebin Han, Hee Min Yoo, Jinha Yu
Summary: This study discovered that compound 9c has the ability to inhibit cell viability and induce cell death in lung cancer cell lines. Additionally, a molecular docking study predicted the binding mode of these derivatives to hA(1) and hA(3) receptors.
Article
Chemistry, Medicinal
Mai Nguyen, Seungchan An, Yen Nguyen, Young Eum Hyun, Hongseok Choi, Linh Pham, Jung-Ae Kim, Minsoo Noh, Gyudong Kim, Lak Shin Jeong
Summary: In this study, L-nucleoside analogues were synthesized using computer-aided design and were found to exhibit enhanced adiponectin-secretion-promoting activity and improved PPAR binding activities compared to n-nucleoside analogues.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Medicinal
Jinha Yu, Ji Won Kim, Girish Chandra, Noriko Saito-Tarashima, Yuhei Nogi, Masashi Ota, Noriaki Minakawa, Lak Shin Jeong
Summary: In order to increase the stability of oligonucleotides, researchers added 2'-OMe modification to previously developed 4'-selenonucleoside and 5'-homo-4'-selenonucleoside. Oligonucleotides containing the chemically modified 4'-selenouridine were synthesized and their thermal stability and nuclease resistance were evaluated. The oligonucleotide containing 5'-homo-2'-OMe-4'-selenouridine showed increased nuclease stability but decreased thermal stability.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Biochemistry & Molecular Biology
Youngchai Son, Jaeyeal Kim, Yongchan Kim, Sung -Gil Chi, Tackhoon Kim, Jinha Yu
Summary: Disruption of protein-protein interaction between TEAD and YAP/TAZ is a potential therapeutic strategy against solid tumors. Novel TEAD-YAP interaction inhibitors were designed and synthesized, and amide derivative 11q exhibited higher potency in inhibiting TEAD-YAP activity and breast cancer cell growth.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Young Eum Hyun, Dnyandev B. Jarhad, Minjae Kim, Ayeon Yang, Gyudong Kim, Hong-Rae Kim, Lak Shin Jeong
Summary: This study reports a concise synthetic route for the key amino sugar intermediate essential for the synthesis of (S)-MC ribonucleosides in a 100% stereoselective manner, and also the first synthesis of enantiomerically pure (S)-MC cytidine 1. These findings are expected to make significant contributions to the field of nucleoside chemistry and provide opportunities for novel nucleoside discovery.
Article
Chemistry, Organic
Chaebin Han, Sun Choi, Jinha Yu
Summary: The study presents a novel method for the synthesis of urea-substituted nucleobases and nucleosides without isocyanates. The reaction involved the use of DMAP and TBPP, resulting in moderate to good yields of various urea-substituted nucleobases and nucleosides. Notably, N6-(N-threonyl-carbonyl) adenosine was also successfully synthesized using this method. These findings provide a facile approach for the synthesis of urea-functionalized nucleobases and nucleosides with potential applications in various fields.
Article
Chemistry, Multidisciplinary
Lan Phuong Nguyen, Rasel Ahmed Khan, Soomin Kang, Hobin Lee, Jong-Ik Hwang, Hong-Rae Kim
Summary: In this study, potential new structures of LPAR1 antagonists were discovered through high-throughput virtual screening. Five structures were identified and validated using an LPAR1-dependent calcium flux assay. The crystal structures showed superior performance in structure-based virtual screening compared to a predictive model. Furthermore, improving precision in the screening process did not necessarily enhance the enrichment of hits. The analysis of protein-ligand interactions laid the groundwork for the discovery of novel LPAR1 antagonists.
Article
Chemistry, Organic
Kisu Sung, Vikas R. Aswar, Jiyoon Song, Dnyandev B. Jarhad, Lak Shin Jeong
Summary: We describe an efficient and stereoselective synthesis method for 1'-substituted-beta-carbocylic nucleosides using gem-dichlorooxirane intermediate to directly condense with weak nucleophiles. This method provides a general and modular approach for the late-stage diversification of 1'-modified nucleosides.
Article
Chemistry, Organic
Gibae Kim, Grim Lee, Gyudong Kim, Yeonseong Seo, Dnyandev B. Jarhad, Lak Shin Jeong
Summary: An efficient methodology for regioselective Sonogashira cross-coupling of 9-substituted 2,8-diiodopurines has been developed, where the regioselectivity is controlled by the ligand in the palladium catalyst. When monodentate ligands like Pd(PPh3)(4) were used, Sonogashira alkynylation preferred the C2-I bond (C2-selective product). However, by using catalysts such as Pd-2(dba)(3)center dot CHCl3 or palladium catalysts with bidentate or electron-rich monodentate phosphine ligands, the preferred coupling site was switched from the C2 position to the C8 position.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Oncology
Yuxin Liu, Swati Bhardwaj, Keith Sigel, John Winters, Joseph Terlizzi, Michael M. Gaisa
Summary: This study investigated the prevalence and severity of anal HPV disease among MSM LWH under the age of 35, finding a high prevalence of HPV infection and precancer but no cases of invasive anal cancer. This supports the adoption of age-based anal cancer screening for this population.
INTERNATIONAL JOURNAL OF CANCER
(2024)
Correction
Oncology
J. Gu, S. Xie, S. Wang
INTERNATIONAL JOURNAL OF CANCER
(2024)