Article
Biochemistry & Molecular Biology
Patricia Camara-Sanchez, Zamira Diaz-Riascos, Natalia Garcia-Aranda, Petra Gener, Joaquin Seras-Franzoso, Micaela Giani-Alonso, Miriam Royo, Esther Vazquez, Simo Schwartz Jr, Ibane Abasolo
Summary: This study aimed to find potential drugs targeting cancer stem cells (CSCs) in triple negative breast cancer (TNBC). The results showed that 8-quinolinol (8Q) and niclosamide (NCS) exhibited significant anti-CSC activity in vitro and in vivo, and had a synergistic effect with PTX in inhibiting the proliferation of cancer cells and viability of CSCs. Additionally, the combination of NCS and PTX reduced tumor growth and metastasis. These findings provide new insights for the development of more effective treatments for TNBC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Ji Hyeon Kim, Soeun Park, Eunsun Jung, Jinwoo Shin, Yoon-Jae Kim, Ji Young Kim, Jonathan L. Sessler, Jae Hong Seo, Jong Seung Kim
Summary: Chemotherapy rarely eradicates cancer stem cells (CSCs) that drive metastatic recurrence. A prodrug, Nic-A, was developed to target triple-negative breast cancer (TNBC) CSCs and inhibit their characteristics. Nic-A showed effectiveness in inhibiting both proliferating TNBC cells and CSCs, leading to decreased stem-like subpopulations and tumor growth. This study highlights a potential strategy for addressing CSC-based cancer recurrence.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Biochemistry & Molecular Biology
Mehran Pashirzad, Thozhukat Sathyapalan, Afsana Sheikh, Prashant Kesharwani, Amirhossein Sahebkar
Summary: This review summarizes the current understanding of CRC-SCs in the progression of CRC and the prognostic importance of these CSCs and their markers in colorectal cancer. Moreover, various therapeutic approaches against markers-expressing CRC SC are also discussed.
PROCESS BIOCHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Fernanda Andrade, Diana Rafael, Mireia Vilar-Hernandez, Sara Montero, Francesc Martinez-Trucharte, Joaquin Seras-Franzoso, Zamira Diaz-Riascos, Ana Boullosa, Natalia Garcia-Aranda, Patricia Camara-Sanchez, Diego Arango, Marika Nestor, Ibane Abasolo, Bruno Sarmento, Simo Schwartz
Summary: The use of CD44v6-targeted polymeric micelles loaded with niclosamide shows promise as a therapeutic strategy against colorectal cancer stem cells and circulating tumor cells, with potential to improve clinical outcomes.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Cell & Tissue Engineering
Xueyue Wang, Yan Ruan, Junlei Zhang, Yanping Tian, Lianlian Liu, JiaLi Wang, Gaoke Liu, Yuda Cheng, Yixiao Xu, Yi Yang, Meng Yu, Binyu Zhao, Yue Zhang, Jiaqi Wang, Jiangjun Wang, Wei Wu, Ping He, Lan Xiao, Jiaxiang Xiong, Rui Jian
Summary: The study identifies two Yap splicing isoforms in ESCs with different distributions and effects on self-renewal and differentiation potential, with Yap472 playing a more essential role in neuroectoderm differentiation.
Article
Anatomy & Morphology
Li Xu, Caixia Ji, Tingting Yu, Jinyong Luo
Summary: Diseases such as bone nonunion and osteoporosis seriously impact people's quality of life, and bone tissue engineering using mesenchymal stem cells is an effective solution. Previous studies have shown the efficacy of BMP9 in promoting osteogenic differentiation of MSCs, but the underlying mechanisms remain unclear. This study investigated the role of Gli1 and Gli2 in BMP9-induced osteogenic differentiation of MSCs. The results demonstrated that inhibition of Gli1 and Gli2 weakened BMP9-induced osteogenic differentiation and reduced the expression of key osteogenic markers, as well as the activation of p-Smad1/5/8 and p-p38 induced by BMP9. In conclusion, this study highlights the importance of Gli1 and Gli2 in BMP9-induced osteogenic differentiation.
Article
Dentistry, Oral Surgery & Medicine
Xinhai Lin, Haodong Wang, Tiantian Wu, Yaqin Zhu, Long Jiang
Summary: These findings suggest that exosomal miR-126 derived from SCAPs under hypoxia can enhance HUVEC angiogenesis by suppressing SPRED1 and activating the ERK signaling pathway.
Article
Medicine, Research & Experimental
Rajani Rai, Debasish Kumar Dey, Doris Mangiaracina Benbrook, Vishal Chandra
Summary: Endometrial cancer, the most common female cancer, lacks effective treatment options. In this study, the anti-cancerous activity of niclosamide (NIC) against endometrial cancer was evaluated. NIC effectively suppressed the viability, migration, and invasion of endometrial cancer cells by inhibiting the AKT/mTOR signaling pathway and inducing apoptosis and autophagy. NIC also inhibited tumor growth in a mouse xenograft model. These findings suggest that NIC could be a promising therapeutic agent for endometrial cancer.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Medicine, Research & Experimental
Maha Al-Tamimi, Abdul Q. Khan, Rasheeda Anver, Fareed Ahmad, Jericha M. Mateo, Syed Shadab Raza, Majid Alam, Joerg Buddenkotte, Martin Steinhoff, Shahab Uddin
Summary: This study explored the underlying mechanisms of pristimerin-induced programmed cell death in squamous cell carcinoma cells. The results showed that pristimerin inhibits the growth and proliferation of cancer cells through JNK activation, and induces cell death via apoptosis and autophagy. Moreover, pristimerin sensitizes cancer cells to conventional anticancer drugs through ROS-mediated JNK activation.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Biotechnology & Applied Microbiology
Xiaoning Qin, Hongxun Ruan, Liqing Yuan, Lin Lin
Summary: This study demonstrates that colorectal cancer stem cells play a significant role in bevacizumab resistance, and inhibiting the IL-22/STAT3 signaling pathway can enhance the anti-tumor effect of bevacizumab.
Review
Cell Biology
Vanessa M. Ruscetta, Taj J. J. Seaton, Aleen Shakeel, Stanley N. S. Vasconcelos, Russell D. D. Viirre, Marc J. J. Adler, Michael F. F. Olson
Summary: Cytoskeleton organization and dynamics are regulated by post-translational modifications of key target proteins, including the phosphorylation of myosin light chain proteins by MRCK kinases. Compared to ROCK kinases, the contributions of MRCK kinases are less characterized due to the late discovery of selective inhibitors. The recent development of selective MRCK inhibitors has expanded the tools to study MRCK function and shown therapeutic benefits in cancer studies.
Article
Cell Biology
Yi-Fong Chen, Yung-Ning Yang, Hung-Ru Chu, Tung-Yung Huang, Shwu-Huey Wang, Han-Yu Chen, Zi-Lin Li, Yu-Chen S. H. Yang, Hung-Yun Lin, Aleck Hercbergs, Jacqueline Whang-Peng, Kuan Wang, Paul J. Davis
Summary: The study reveals that doxycycline inhibits proliferation and downregulates PD-L1 gene expression in breast cancer cells, possibly by interacting with integrin alpha v beta 3 and inhibiting ERK1/2 activation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Geoff P. O'Donoghue, Lukasz J. Bugaj, Warren Anderson, Kyle G. Daniels, David J. Rawlings, Wendell A. Lim
Summary: T cells are able to pick out antigenic signals and establish self-tolerance from complex temporal patterns of stimulus. By engineering T cells to respond to light as a stimulus, researchers found that T cells can filter out minute-scale oscillations of activation signal. CD69 expression reached a local minimum at a period of around 25 minutes, suggesting a potential frequency filtering mechanism downstream of the Erk signaling branch. This study highlights the ability of T cell signaling machinery to temporally filter and interpret time-variant input signals in discriminatory ways.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Geoff P. O'Donoghue, Lukasz J. Bugaj, Warren Anderson, Kyle G. Daniels, David J. Rawlings, Wendell A. Lim
Summary: T cells experience complex temporal patterns of stimulation through receptor-ligand-binding interactions with surrounding cells, enabling them to pick out antigenic signals and establish self-tolerance. This study demonstrates that T cells are able to respond to minute-scale oscillations of activation signal and interpret time-variant input signals through a frequency filtering mechanism downstream of the Erk signaling branch. Temporal filtering may play a functional role in vivo, as indicated by observed T cell encounters with self-peptide-presenting antigen-presenting cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Pharmacology & Pharmacy
Ganesan Shilpa, Sreerenjini Lakshmi, Vellekkatt Jamsheena, Ravi Shankar Lankalapalli, Ved Prakash, Sadasivam Anbumani, Sulochana Priya
Summary: The study shows that two synthetic biaryl conjugates of diindolylmethane (DIM) exhibit cytotoxicity in triple negative breast cancer cells, inducing apoptosis and inhibiting cell migration and metastasis. This is achieved by blocking the EGF receptor and modulating the PI3K-Akt-mTOR signaling pathway.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2022)
Article
Chemistry, Medicinal
Xiaoyun Lu, Jeff B. Smaill, Ke Ding
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Chemistry, Multidisciplinary
Nan Ma, Jun Hu, Zhi-Min Zhang, Wenyan Liu, Minhao Huang, Youlong Fan, Xingfeng Yin, Jigang Wang, Ke Ding, Wencai Ye, Zhengqiu Li
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2020)
Article
Pharmacology & Pharmacy
Liang Jiang, Yuting Wang, Qian Li, Zhengchao Tu, Sihua Zhu, Sanfang Tu, Zhang Zhang, Ke Ding, Xiaoyun Lu
Summary: A new class of selective Bcr-Abl(T315I) proteolysis-targeting chimeric degraders were designed, synthesized, and evaluated, with 7o exhibiting the most potent degradation efficacy and significant tumor regression in cell and animal models.
ACTA PHARMACEUTICA SINICA B
(2021)
Editorial Material
Chemistry, Medicinal
Craig W. Lindsley, James Barrow, Kelly Chibale, Maria Laura Bolognesi, Stuart Conway, William Denny, Ke Ding, Stefan Laufer, Luhua Lai, Hong Liu, Nouri Neamati, Takayoshi Suzuki, Nicholas Meanwell, Wendy Young
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Kaili Jiang, Xia Tang, Jing Guo, Rui He, Shingpan Chan, Xiaojuan Song, Zhengchao Tu, Yuting Wang, Xiaomei Ren, Ke Ding, Zhang Zhang
Summary: GZD824, a third generation ABL inhibitor, has been shown to overcome FGFR1-V561F/M mutant resistance in vitro and in vivo, suggesting its potential efficacy for treating patients with FGFR1 abnormal activation or mutant resistance in clinical trials.
Article
Chemistry, Medicinal
Xiaoyun Lu, Jeff B. Smaill, Adam Patterson, Ke Ding
Summary: Small molecule covalent kinase inhibitors (CKIs) have advantages for sustained target inhibition and high selectivity, with major medicinal chemistry strategies involving the addition of a warhead to a reversible lead/inhibitor scaffold to generate CKIs, while also facing challenges in drug discovery in this area.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Zhen Zhang, Jie Li, Hao Chen, Jing Huang, Xiaojuan Song, Zheng-Chao Tu, Zhang Zhang, Lijie Peng, Yang Zhou, Ke Ding
Summary: Aberrant FGF19/FGFR4 signaling has been identified as an oncogenic driver for human hepatocellular carcinoma (HCC). A new series of inhibitors targeting FGFR4 have been synthesized, and the representative compound 9ka showed potent activity against FGFR4 with excellent kinome selectivity. Compound 9ka also demonstrated favorable pharmacokinetic properties and induced significant tumor regression in a mouse model without apparent toxicity. Compound 9ka may serve as a promising lead compound for further development of anticancer drugs.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Jibu Lu, Yongjun Huang, Jing Huang, Rui He, Minhao Huang, Xiaoyun Lu, Yong Xu, Fengtao Zhou, Zhang Zhang, Ke Ding
Summary: The first examples of threonine tyrosine kinase (TTK) PROTACs were successfully designed and synthesized, showing strong degradation effects in human colorectal cancer cells and potential anticancer activities.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Zhen Wang, Weixue Huang, Kaijie Zhou, Xiaomei Ren, Ke Ding
Summary: Protein kinases have been proven to be effective targets for cancer drug discovery, but most drugs inhibit kinase catalytic activity by binding to ATP-site. Recent studies have shown that kinases also have noncatalytic functions, which play important roles in cellular signaling and cell fate controls. Small-molecule modulators targeting the noncatalytic functions of kinases have emerged as promising therapeutic strategies. This article summarizes the noncatalytic functions of kinases and discusses the progress in developing small-molecule modulators. It is speculated that targeting the noncatalytic functions could open a new direction for kinase-based drug discovery.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Peng Lyu, Kaili Jiang, Yuee Zhou, Jun Hu, Yu Chang, Zhang Zhang, Minhao Huang, Zhi-Min Zhang, Ke Ding, Piliang Hao, Ligen Lin, Zhengqiu Li
Summary: This study successfully identified the cellular off-target NT5DC1 of HP-1, a potential drug candidate for non-small cell lung cancer, through chemical proteomics and bioimaging studies.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Medicinal
Zuqin Wang, Jie Wang, Yongjin Wang, Shuang Xiang, Xiaojuan Song, Zhengchao Tu, Yang Zhou, Zhi-Min Zhang, Zhang Zhang, Ke Ding, Xiaoyun Lu
Summary: In this study, a novel TRK inhibitor 7b was reported. It is a highly selective macrocycle-based potent type II inhibitor that exhibits high inhibitory activity against TRK fusion proteins and wild type. Additionally, 7b showed potent antiproliferative activity against various mutants and displayed extraordinary selectivity for phosphorylation.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Yue Liu, Jiacong Liu, Xianfang Zhang, Cuiping Guo, Zhi-Min Zhang, Xiwen Xing, Ke Ding, Zhengqiu Li
Summary: Chemical proteomics is a powerful technology for studying uncharacterized proteins in the human proteome. A new protein-labeling strategy using nitrile oxide has been developed, which can efficiently react with target proteins. This method has shown excellent chemoselectivity and successfully characterized over 4000 cysteine residues, including KRAS G12C, demonstrating its complementary utility.
ACS CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Medicinal
Yiying Wei, Xinxin Xu, Minchuan Jiang, Yongxing Wang, Yang Zhou, Zhen Wang, Zhang Zhang, Fengtao Zhou, Ke Ding
Summary: A new selective GSPT1 degrader was developed, which could effectively degrade GSPT1 and showed good selectivity in the global proteomic profiling study. The compound also displayed good antiproliferative activities and induced cell cycle arrest and apoptosis in U937 cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Shumin Lv, Fang Xu, Youlong Fan, Ke Ding, Zhengqiu Li
Summary: Due to the limited targets for drug development, triple-negative breast cancer (TNBC) is considered a challenging disease for chemotherapy. In this study, a set of novel electrophilic warheads was used to search for potential targets for TNBC in chemical proteomics studies. These warheads were found to modify not only highly nucleophilic residues but also weakly nucleophilic residues. Cys12 of Kirsten rat sarcoma (KRASG12C) was successfully labeled by cyclopropenone and cyclopropeniminium ions. Preliminary results showed moderate inhibitory activity against TNBC cells with these electrophile-based probes, and FABP5 was identified as a potential target for TNBC through further functional validation experiments.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Zuqin Wang, Jie Wang, Yongjin Wang, Shuang Xiang, Hengliang Zhou, Shukai Song, Xiaojuan Song, Zhengchao Tu, Yang Zhou, Ke Ding, Zhi-Min Zhang, Zhang Zhang, Xiaoyun Lu
Summary: This study focuses on the development of new type II TRK inhibitors to combat acquired resistance mutations. Compound 10g displayed excellent potency against TRK mutants and demonstrated strong inhibition of cell proliferation. The results provide a promising lead compound for pan-anticancer drug discovery.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
