Article
Chemistry, Medicinal
Jingbo Zhang, Huimin Jiang, Songwen Lin, Deyu Wu, Hua Tian, Lin Jiang, Yiman Cui, Jing Jin, Xiaoguang Chen, Heng Xu
Summary: In this study, novel and selective PI3Kδ inhibitors were designed and synthesized, among which compound 6 showed significant anticancer activity in cellular and mouse models, making it a promising candidate for the treatment of B-cell malignancies.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Xiaofei Liang, Chun Wang, Beilei Wang, Juan Liu, Shuang Qi, Aoli Wang, Qingwang Liu, Maoqing Deng, Li Wang, Jing Liu, Qingsong Liu
Summary: CSF1R kinase is crucial in tumor-associated macrophage repolarization, and the selective inhibitor 18h shows potent inhibition against CSF1R with significant selectivity, leading to suppression of tumor growth.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Xiaobao Fang, Chunxiao Liu, Kun Zhang, Wanping Yang, Zewen Wu, Shige Shen, Yule Ma, Xun Lu, Yadong Chen, Tao Lu, Qinghua Hu, Yulei Jiang
Summary: This study discovered a series of novel, potent, and selective covalent BTK inhibitors through structure-based drug design, among which compound 36R exhibited high kinase selectivity, long target occupancy time, appropriate pharmacokinetic properties, and dose-dependent efficacy in a rat model of collagen-induced arthritis. Therefore, 36R is a novel BTK inhibitor requiring further development for the treatment of autoimmune diseases.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Medicine, Research & Experimental
Xianbo Wu, Jie Wang, Qi Liang, Rongsheng Tong, Jianli Huang, Xinwei Yang, Yihua Xu, Wenjing Wang, Minghan Sun, Jianyou Shi
Summary: FAK is an important target for cancer treatment, and many small molecule inhibitors have shown efficacy in inhibiting tumor growth and metastasis. Dual inhibitors that block FAK and other factors simultaneously can improve therapeutic efficacy and overcome drug resistance.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Chemistry, Medicinal
Shihe Hu, Cuihua Jiang, Meng Gao, Dongjian Zhang, Nan Yao, Jian Zhang, Qiaomei Jin
Summary: A series of pyrazolo[3,4-b]pyridine-based compounds were investigated as new Mps1 inhibitors through virtual screening, chemical synthesis, and biological evaluation. The representative compound, 31, showed strong inhibitory potency against Mps1 and significantly inhibited the proliferation of cancer cells, especially MDA-MB-468 and MV4-11 cells. Compound 31 also exhibited reasonable kinome selectivity and promising pharmacokinetic and pharmacodynamic profiles. Furthermore, it displayed good antitumor efficacy in a xenograft model without obvious toxicity. Compound 31 is identified as a potential Mps1 inhibitor for cancer therapy and warrants further research.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Seyed-Omar Zaraei, Nour N. Al-Ach, Hanan S. Anbar, Randa El-Gamal, Hamadeh Tarazi, Rimas T. Tokatly, Rawan R. Kalla, Mouna A. Munther, Marwa M. Wahba, Aya M. Alshihabi, Mahmoud K. Shehata, Rawan M. Sbenati, Afnan I. Shahin, Raafat El-Awady, Taleb H. Al-Tel, Mohammed I. El-Gamal
Summary: This article presents the design, synthesis, and biological screening results of a new series of diarylurea and diarylamide derivatives with a quinoline core armed with dimethylamino or morpholino side chains. The compounds showed broad-spectrum antiproliferative activity against a panel of 60 cancer cell lines, with three of them demonstrating higher potency than the reference drug, sorafenib. The compounds also exhibited high selectivity for C-RAF kinase, making them potential inhibitors for this molecular target.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Xiaojing Chen, Lu Liu, Peng Liu, Yingying Chen, Dan Lin, Hao Yan, Qi Yan, Yi Wang, Yinda Qiu, Bo Fang, Huijing Huang, Jianchang Qian, Yunjie Zhao, Zhou Du, Qianwen Zhang, Xiaokun Li, Xiaohui Zheng, Zhiguo Liu
Summary: This study investigated the design, synthesis, and structure-activity relationships of novel pyrimidine-2,4-diamine derivatives that selectively inhibit PDGFR alpha/beta kinases. Compound 7m showed the most promising activity against PDGFR alpha and beta, with low IC50 values. It also exhibited significant cytotoxic effects against osteosarcoma cancer cell lines, as well as robust antitumor effects and low toxicity in a xenograft model. The compound demonstrated favorable pharmacokinetic properties and showed potential as a drug candidate for PDGFR-driven osteosarcoma.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
K. P. Cusack, M. A. Argiriadi, T. D. Gordon, C. M. Harris, J. M. Herold, M. Z. Hoemann, B. D. Yestrepsky
Summary: PKR inhibition is important in immunology and neuroscience. However, existing compounds lack selectivity. This study used virtual screening and compound design to identify more selective leads for investigating PKR biology.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Medicinal
Hongchao Zheng, Jichen Zhao, Bing Li, Weihe Zhang, Michael A. Stashko, Katherine A. Minson, Madeline G. Huey, Yubai Zhou, Henry Shelton Earp, Dmitri Kireev, Douglas K. Graham, Deborah DeRyckere, Stephen Frye, Xiaodong Wang
Summary: Inhibition of MER receptor tyrosine kinase (MERTK) contributes to tumor cell killing and stimulation of the immune response. UNC5293 is a highly selective MERTK inhibitor with potent and selective inhibition in cell-based assays, excellent mouse PK properties, and activity in leukemia cells in a murine model.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Pengxing He, Jing Jing, Linna Du, Xuyang Zhang, Yufei Ren, Han Yang, Bin Yu, Hongmin Liu
Summary: YS-363 is a novel EGFR inhibitor that demonstrates potent reversible inhibition and excellent activities against cell proliferation, migration, cell cycle and apoptosis. It is a promising selective inhibitor that can potentially be developed as a more effective anti-lung cancer agent targeting EGFR.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Chemistry, Medicinal
Chengbin Yang, Chenyue Xu, Zhipeng Li, Yi Chen, Tianze Wu, Hui Hong, Mingzhu Lu, Yu Jia, Yongtai Yang, Xiaofeng Liu, Mingli Deng, Zhenxia Chen, Qingquan Li, Yun Ling, Yaming Zhou
Summary: FD223, a potent and selective PI3K delta inhibitor developed based on the indole scaffold, showed high potency and selectivity against PI3K delta in AML cell lines, with favorable in vivo antitumor efficacy and no observable toxicity, indicating its potential for further development as a promising treatment for leukemia such as AML.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Seyed-Omar Zaraei, Rawan M. Sbenati, Nour N. Alach, Hanan S. Anbar, Randa El-Gamal, Hamadeh Tarazi, Mahmoud K. Shehata, Mohammed S. Abdel-Maksoud, Chang-Hyun Oh, Mohammed El-Gamal
Summary: This article reports on novel imidazothiazole derivatives as first-in-class potent and selective ErbB4 (HER4) inhibitors. The compounds showed promising antiproliferative activity with high selectivity towards cancer cell lines, indicating potential therapeutic value.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Peter Q. Huang, Brant C. Boren, Sayee G. Hegde, Hui Liu, Aditya K. Unni, Sunny Abraham, Chad D. Hopkins, Sunil Paliwal, Ahmed A. Samatar, Jiali Li, Kevin D. Bunker
Summary: Wee1 inhibition has emerged as a promising therapy for cancer treatment in the past decade. Compound 16, a highly selective Wee1 inhibitor with balanced potency and pharmacokinetic properties, has shown excellent in vivo efficacy and is currently in phase 2 clinical trials.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Yumeng Zhang, Shu Liu, Shu Zhou, Dandan Yu, Junjie Gu, Qin Qin, Yu Cheng, Xinchen Sun
Summary: Oesophageal cancer is highly invasive and prone to recurrence and metastasis, with a low five-year survival rate, making the development of new therapeutic interventions crucial. Focal adhesion kinase (FAK) plays a key role in survival, proliferation, and migration of cancer cells, making it a potential therapeutic target for oesophageal cancer. The combination of FAK inhibitors with other treatments is expected to improve patient survival.
Article
Biochemistry & Molecular Biology
Fei Hou, Yuhong Yao, Yujiao Wei, Yubo Wang, Yangzi Cao, Xinqiang Liu, Liting Zheng, Qingqing Zhang, Yue Jiao, Yukun Chen, Yue Meng, Yue Sun, Yanjie Wu, Jiefu Wang, Junfeng Wang, Zhou Wu, Kun Zhang, Mingming Wei, Guang Yang
Summary: A series of novel substituted 4-anilinoquinazolines and their related compounds were designed and prepared as potential inhibitors of VEGFR-2 using 3D modeling. Compound I10 showed more potent inhibitory activity (IC50 = 0.11 nM) against VEGFR-2 compared to most listed drugs, and it was confirmed as a selective VEGFR-2 inhibitor. 3D modeling predicted a unique binding mode of this lead compound to VEGFR-2. Compound I10 exhibited remarkable antiangiogenesis and anti-proliferation effects in HUVEC at low nanomolar concentrations, and PK studies showed adequate oral bioavailability. In vivo subcutaneous tumor model demonstrated potent efficacy of I10 in inhibiting tumor growth and angiogenesis, indicating its potential as a drug candidate for cancer treatment.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Diego de Miguel-Perez, Edward M. Pickering, Umberto Malapelle, William Grier, Francesco Pepe, Pasquale Pisapia, Gianluca Russo, Joseph A. Pinto, Alessandro Russo, Giancarlo Troncone, Melissa J. Culligan, Katherine A. Scilla, Ranee Mehra, Pranshu Mohindra, Oscar Arrieta, Andres F. Cardona, Marzia Del Re, Ashutosh Sachdeva, Fred R. Hirsch, Andrea Wolf, Joseph S. Friedberg, Christian Rolfo
Summary: In this study, genetic alterations in resectable pleural mesothelioma tissues and blood samples were analyzed, and it was found that high tissue tumor mutational burden, tissue median minor allele frequency, blood tumor mutational burden, and specific mutations were correlated with outcomes in patients with resected PM. These findings suggest that molecular profiling could help identify longer survivors in patients with resected PM.
EUROPEAN JOURNAL OF CANCER
(2024)
Article
Oncology
Davide Melisi, Camilla Zecchetto, Valeria Merz, Giuseppe Malleo, Luca Landoni, Alberto Quinzii, Simona Casalino, Federica Fazzini, Marina Gaule, Camilla Pesoni, Luca Casetti, Alessandro Esposito, Giovanni Marchegiani, Cristiana Piazzola, Mirko D'Onofrio, Riccardo de Robertis, Armando Gabbrielli, Laura Bernardoni, Stefano F. Crino, Silvia Pietrobono, Claudio Luchini, Camillo Aliberti, Guido Martignoni, Stefano Milleri, Giovanni Butturini, Aldo Scarpa, Roberto Salvia, Claudio Bassi
Summary: This study evaluated the safety and activity of liposomal irinotecan in the perioperative treatment of resectable pancreatic ductal adenocarcinoma (rPDAC) patients. The results showed that NALIRIFOX has manageable and active outcomes, and should be further investigated in randomized trials comparing it to standard upfront surgery followed by adjuvant therapy.
EUROPEAN JOURNAL OF CANCER
(2024)
Article
Oncology
Eric Jonasch, Todd M. Bauer, Kyriakos P. Papadopoulos, Elizabeth R. Plimack, Jaime R. Merchan, David F. Mcdermott, M. Dror Michaelson, Leonard J. Appleman, Ananya Roy, Rodolfo F. Perini, Yanfang Liu, Toni K. Choueiri
Summary: After a median follow-up of 41.2 months, belzutifan monotherapy demonstrated durable antitumor activity in patients with advanced ccRCC and acceptable safety.
EUROPEAN JOURNAL OF CANCER
(2024)
Article
Oncology
Patricia A. H. Hamers, Geraldine R. Vink, Marloes A. G. Elferink, Leon M. G. Moons, Cornelis J. A. Punt, Anne M. May, Miriam Koopman
Summary: Screen-detection of the primary tumor is associated with longer overall survival after metachronous metastasis.
EUROPEAN JOURNAL OF CANCER
(2024)
Article
Oncology
Camilla Nero, Nicolo Bizzarri, Stefano Di Berardino, Francesca Sillano, Giuseppe Vizzielli, Francesco Cosentino, Virginia Vargiu, Pierandrea De Iaco, Anna Myriam Perrone, Enrico Vizza, Benito Chiofalo, Stefano Uccella, Fabio Ghezzi, Luigi Carlo Turco, Giacomo Corrado, Diana Giannarelli, Tina Pasciuto, Gian Franco Zannoni, Anna Fagotti, Giovanni Scambia
Summary: This study evaluates the sensitivity and specificity of sentinel-lymph-node mapping compared to systematic lymphadenectomy in detecting lymph node metastasis in early stage ovarian cancer. The results show that sentinel-lymph-node mapping did not reach the expected sensitivity, but ultra-staging protocol improved the accuracy of diagnosis for patients.
EUROPEAN JOURNAL OF CANCER
(2024)
Article
Oncology
Adriana Hepner, Judith M. Versluis, Roslyn Wallace, Clara Allayous, Lauren Julia Brown, Claudia Trojanielloh, Camille Lea Gerardi, Yanina J. L. Jansenj, Prachi Bhave, Bart Neyns, Andrew Haydon, Olivier Michielin, Joanna Manganan Oliver Klein, Alexander N. Shoushtari, Allison Betof Warner, Paolo Antonio Ascierto, Jennifer Leigh McQuade, Matteo S. Carlino, Lisa Zimmer, Celeste Lebbe, Douglas B. Johnson, Shahneen Sandhu, Victoria Atkinson, Christian U. Blank, Serigne N. Lo, Georgina V. Long, Alexander M. Menzies
Summary: Acquired resistance to PD-1 therapy in melanoma is mainly oligometastatic, and patients may have a favorable survival outcome following salvage treatment.
EUROPEAN JOURNAL OF CANCER
(2024)
Article
Oncology
Savannah Roy, Stephanie Lakritz, Anna R. Schreiber, Elizabeth Molina Kuna, Cathy J. Bradley, Lavanya Kondapalli, Jennifer R. Diamond
Summary: This study evaluates major adverse cardiovascular events (MACE) in older women with TNBC treated with anthracycline and taxane-based chemotherapy (ATAX) compared to taxane-based chemotherapy (TAX). The results show that ATAX does not increase the risk of MACE and there is no difference in survival between patients who received TAX and ATAX.
EUROPEAN JOURNAL OF CANCER
(2024)
Letter
Oncology
Pei-Chun Weng, Yau-Li Huang, Chun-Yu Cheng
EUROPEAN JOURNAL OF CANCER
(2024)
Article
Oncology
Philipp Jansen, Jean Le 'Clerc Arrastia, Daniel Otero Baguer, Maximilian Schmidt, Jennifer Landsberg, Joerg Wenzel, Michael Emberger, Dirk Schadendorf, Eva Hadaschik, Peter Maass, Klaus Georg Griewank
Summary: This study highlights the enormous potential of artificial intelligence in pathology, showing that it can aid in the identification of rare cutaneous adnexal tumors and potentially become a standard tool in routine diagnostics.
EUROPEAN JOURNAL OF CANCER
(2024)
Article
Oncology
Casper W. F. van Eijck, Gaby Strijk, Eveline E. Vietscha, Fleur van der Sijde, Maaike Verheij, Dana A. M. Mustafa, Madelief Vinkc, Joachim G. J. V. Aerts, Casper H. J. van Eijck, Marcella Willemsen
Summary: The study reveals that FOLFIRINOX has immunomodulatory effects, suggesting its potential in immune-based combination therapies for pancreatic cancer. Additionally, certain plasma proteins hold promise as circulating predictive biomarkers for early prediction of FOLFIRINOX response in patients with pancreatic cancer.
EUROPEAN JOURNAL OF CANCER
(2024)
Article
Oncology
Marwan Fakih, Chongkai Wang, Jaideep Sandhu, Jian Ye, Colt Egelston, Xiaochen Li
Summary: This study explores the impact of metastatic sites on treatment outcomes for chemotherapy-refractory colorectal cancer patients. It found that patients with liver or peritoneal metastases had poor treatment outcomes, while those with lung-only metastases showed significant response. The presence of concurrent lymph node or other extrahepatic metastatic disease diminished treatment response in patients with lung metastases. Future checkpoint inhibitor trials should stratify patients based on metastatic locations.
EUROPEAN JOURNAL OF CANCER
(2024)
Article
Oncology
Georgios Christos Tsiatsianis, Candace S. Y. Chan, Ioannis Mouratidis, Nikol Chantzi, Anna Maria Tsiatsiani, Nelson S. Yee, Apostolos Zaravinos, Verena Kantere, Ilias Georgakopoulos-Soares
Summary: The study reveals that nullpeptides can serve as biomarkers for cancer detection and treatment, particularly in highly recurrent cancer patients. These nullpeptides primarily occur in highly expressed genes, particularly in specific loci of oncogenes and tumor suppressors. Recurrent nullpeptides are more likely to be found in neoantigens, which play a significant role in immunotherapy.
EUROPEAN JOURNAL OF CANCER
(2024)