Article
Oncology
Susi Zhu, Yeye Guo, Xu Zhang, Hong Liu, Mingzhu Yin, Xiang Chen, Cong Peng
Summary: PKM2 plays a crucial role in tumor metabolism and its dysregulation is associated with cancer development and progression. Researchers are investigating the function and therapeutic potential of PKM2 in cancer, particularly its interactions with lncRNAs. The role of PKM2 in the tumor microenvironment (TME) is also being studied for its implications in cancer therapy.
Article
Chemistry, Medicinal
Xingchen Liu, Cheng Wang, Shang Li, Lailiang Qu, Fucheng Yin, Dehua Lu, Heng Luo, Xinye Chen, Zhongwen Luo, Ningjie Cui, Xiaobing Wang, Lingyi Kong
Summary: In this study, a potential drug candidate 29e for treating CRC was designed to inhibit tumor growth by targeting PKM2 kinase, demonstrating significant antiproliferative effects in cell experiments and animal models.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Yong Xia, Xing Wang, Yan Liu, Ellen Shapiro, Herbert Lepor, Moon-shong Tang, Tung-Tien Sun, Xue-Ru Wu
Summary: PKM2 plays an essential role in promoting tumor growth and maintenance by enhancing angiogenesis and metabolic addiction, although it is not required for tumor initiation. The PKM2-STAT3-HIF1 alpha/VEGF signaling axis may be critical in bladder cancer and could be a potential therapeutic target.
Article
Multidisciplinary Sciences
Hongwei Han, Yinwei Zhang, Guangda Peng, Liangwei Li, Jenny Yang, Yi Yuan, Yiting Xu, Zhi-Ren Liu
Summary: Myofibroblasts express and secrete PKM2 which activates the FAK-PI3K signaling axis, leading to increased activity of the NF-kappa B survival pathway and resistance to apoptosis, promoting fibrosis development. Disruption of the interaction between PKM2 and integrin alpha(v)beta(3) using an antibody effectively reverses fibrosis.
Review
Medicine, Research & Experimental
Abu Sufiyan Chhipa, Snehal Patel
Summary: Cancer cell transformation results from complex crosstalk between intracellular components and proteins. PKM2 plays crucial roles in cancer growth and modulation of its activity can control cancer progression.
Article
Multidisciplinary Sciences
Shi-Hai Yan, Li-Mu Hu, Xue-Hui Hao, Jiang Liu, Xi-Ying Tan, Zhi-Rong Geng, Jing Ma, Zhi-Lin Wang
Summary: This study revealed the direct binding target protein of berberine in colorectal cancer cells, which is pyruvate kinase isozyme type M2 (PKM2). Berberine inhibits the progression of colorectal cancer through hydrophobic interaction and pi-pi interaction, and it also inhibits the reprogramming of glucose metabolism.
Article
Multidisciplinary Sciences
Yinsheng Wu, Lixu Tang, Han Huang, Qi Yu, Bicheng Hu, Gang Wang, Feng Ge, Tailang Yin, Shanshan Li, Xilan Yu
Summary: This study reveals that glycolysis-derived serine biosynthesis activates PKM2 to prevent cell senescence and promote healthy aging. The expression of serine biosynthetic enzyme PHGDH is reduced during senescence, leading to a decrease in intracellular serine. PHGDH prevents premature senescence primarily by enhancing the stability and activity of PKM2 and regulating the transcription of senescence-associated genes.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Kunmin Zhao, Xingwen Wang, Dong Zhao, Qingyu Lin, Yi Zhang, Ying Hu
Summary: A study found that a long noncoding RNA (lncRNA) called HIF-1 alpha inhibitor at transcription level (HITT) can inhibit lactate production in a pyruvate kinase M2 (PKM2)-dependent manner. HITT physically interacts with PKM2 and inhibits its oligomerization, resulting in a dramatic reduction of PK activity. Additionally, this interaction reduces lactate secretion from cancer cells and polarizes macrophages towards an M2-like anti-inflammatory phenotype, potentially contributing to immune escape.
Article
Medicine, Research & Experimental
Ganesh Satyanarayana, Ravi Chakra Turaga, Malvika Sharma, Siming Wang, Falguni Mishra, Guangda Peng, Xiaonan Deng, Jenny Yang, Zhi-Ren Liu
Summary: This study reveals that differentiation of myofibroblasts upregulates pyruvate kinase M2 (PKM2) and promotes PKM2 dimerization, which slows glycolysis and facilitates collagen synthesis and secretion. PKM2 activator inhibits progression of liver, lung, and pancreatic fibrosis in mouse models, while increasing NADPH production to protect myofibroblasts from apoptosis.
Article
Oncology
Rumeysa Biyik-Sit, Traci Kruer, Susan Dougherty, James A. Bradley, Daniel W. Wilkey, Michael L. Merchant, John O. Trent, Brian F. Clem
Summary: In addition to its traditional role in cellular serine synthesis pathway, PSAT1 has been shown to participate in lung cancer cell migration, mediated by its interaction with PKM2.
Review
Biochemistry & Molecular Biology
Dexter L. Puckett, Mohammed Alquraishi, Winyoo Chowanadisai, Ahmed Bettaieb
Summary: PKM2 plays a significant role in cancer cell metabolism, proliferation, and migration through its inactive dimeric form, while also being essential for cellular homeostasis in non-cancer tissues. Research targeting various tissues beyond cancer, such as the kidney, liver, adipose, and pancreas, contributes to a better understanding of PKM2's functions in different diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Beom-Seok Kang, Bo-Young Choi, A-Ra Kho, Song-Hee Lee, Dae-Ki Hong, Min-Kyu Park, Si-Hyun Lee, Chang-Juhn Lee, Hyeun-Wook Yang, Seo-Young Woo, Se-Wan Park, Dong-Yeon Kim, Jae-Bong Park, Won-Suk Chung, Sang-Won Suh
Summary: Ischemic stroke is caused by insufficient blood flow to the brain. Astrocytes play a crucial role in supplying lactate to neurons through the astrocyte-neuron lactate shuttle (ANLS). The deletion of the pyruvate kinase M2 (PKM2) gene in astrocytes reduces lactate supply and exacerbates neuronal death. Lactate administration can prevent neuronal damage following ischemic stroke by maintaining energy metabolism in neurons through the ANLS.
Article
Biochemistry & Molecular Biology
Gang Zhao, Hang Yuan, Qin Li, Jie Zhang, Yafei Guo, Tianyu Feng, Rui Gu, Deqiong Ou, Siqi Li, Kai Li, Ping Lin
Summary: This study uncovers the significant role of DDX39B in modulating glycolytic reprogramming and aggressive progression in colorectal cancer (CRC). The upregulation of DDX39B is associated with liver metastases and aggressive phenotypes in CRC patients. Mechanistically, DDX39B activates PKM2 by suppressing its ubiquitination and degradation, leading to enhanced glucose uptake and lactate production. DDX39B also accelerates the nuclear translocation of PKM2 to transactivate oncogenes and glycolysis-related genes, promoting CRC growth and metastasis. Furthermore, blocking PKM2 nuclear translocation or glycolytic inhibition efficiently abolishes DDX39B-triggered malignant development in CRC, highlighting DDX39B as a potential therapeutic target.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
Article
Chemistry, Analytical
Ziqian Wang, Xiaodong Zhang, Hong Zhang, Yao Tang, Hao Pan, Hang Wang, Tong Ji, Yafei Guo, Qishuang Gao, Ting Song, Zhichao Zhang
Summary: Researchers have developed a reaction-based fluorescent probe that can selectively label specific protein binding sites, enabling precise in situ detection of protein expression with potential applications in cancer diagnoses.
ANALYTICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Qing Xia, Jing Jia, Chupeng Hu, Jinying Lu, Jiajin Li, Haiyan Xu, Jianchen Fang, Dongju Feng, Liwei Wang, Yun Chen
Summary: This study found that TGF-beta 1 secreted by TAMs promotes the expression of PD-L1 in PDAC cells by inducing nuclear translocation of PKM2. The interaction between PKM2 and STAT1 enhanced by TGF-beta 1 stimulation facilitates the transactivation of PD-L1. Knockdown of PKM2 decreases PD-L1 expression, promotes NK cell activation, inhibits tumor growth, and when combined with PD-1/PD-L1 blockade, limits tumor growth.
Article
Chemistry, Medicinal
Koc-Kan Ho, K. Mark Parnell, Yi Yuan, Yong Xu, Steven G. Kultgen, Steven Hamblin, Thomas F. Hendrickson, Bai Luo, Jason M. Foulks, Michael V. McCullar, Steven B. Kanner
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2013)
Article
Chemistry, Medicinal
Yong Xu, Jason M. Foulks, Adrianne Clifford, Benjamin Brenning, Shuping Lai, Bai Luo, K. Mark Parnell, Shannon Merx, Michael V. McCullar, Steven B. Kanner, Koc-Kan Ho
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2013)
Article
Hematology
Jason M. Foulks, Gopal K. Marathe, Noemi Michetti, Diana M. Stafforini, Guy A. Zimmerman, Thomas M. McIntyre, Andrew S. Weyrich
Meeting Abstract
Oncology
Mark Parnell, Jason M. Foulks, Rebecca Nix, Bai Luo, Anna Senina, Yong Xu, Michael Saunders, Koc-Kan Hol, Michael V. McCullar, Steven B. Kanner
Meeting Abstract
Oncology
Jason M. Foulks, Yong Xu, Michael Saunders, Xiao-Hui Liu, Benjamin Brenning, Adrianne Clifford, Marcus Wilkes, Bai Luo, Shuping Lai, Shannon Merx, Ashley Chan, Liwen Huang, David VolImer, Anna Senina, Jihua Liu, Koc-Kan Ho, Michael V. McCullar, Steven B. Kanner
Article
Biochemistry & Molecular Biology
Jason M. Foulks, Andrew S. Weyrich, Guy A. Zimmerman, Thomas M. McIntyre
FREE RADICAL BIOLOGY AND MEDICINE
(2008)
Article
Oncology
K. Mark Parnell, Jason M. Foulks, Rebecca N. Nix, Adrianne Clifford, Jeremy Bullough, Bai Luo, Anna Senina, David Vollmer, Jihua Liu, Virgil McCarthy, Yong Xu, Michael Saunders, Xiao-Hui Liu, Scott Pearce, Kevin Wright, Marc O'Reilly, Michael V. McCullar, Koc-Kan Ho, Steven B. Kanner
MOLECULAR CANCER THERAPEUTICS
(2013)
Review
Biochemical Research Methods
Jason M. Foulks, K. Mark Parnell, Rebecca N. Nix, Suzanna Chau, Krzysztof Swierczek, Michael Saunders, Kevin Wright, Thomas F. Hendrickson, Koc-Kan Ho, Michael V. McCullar, Steven B. Kanner
JOURNAL OF BIOMOLECULAR SCREENING
(2012)
Article
Biochemistry & Molecular Biology
Jiawei Chen, Lili Yang, Jason M. Foulks, Andrew S. Weyrich, Gopal K. Marathe, Thomas M. McIntyre
JOURNAL OF LIPID RESEARCH
(2007)
Article
Hematology
Andrew S. Weyrich, Melvin M. Denis, Hansjorg Schwertz, Neal D. Tolley, Jason Foulks, Eliott Spencer, Larry W. Kraiss, Kurt H. Albertine, Thomas M. McIntyre, Guy A. Zimmerman
Article
Immunology
Hansjoerg Schwertz, Neal D. Tolley, Jason M. Foulks, Melvin M. Denis, Ben W. Risenmay, Michael Buerke, Rachel E. Tilley, Matthew T. Rondina, Estelle M. Harris, Larry W. Kraiss, Nigel Mackman, Guy A. Zimmerman, Andrew S. Weyrich
JOURNAL OF EXPERIMENTAL MEDICINE
(2006)
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)
