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
Chemistry, Medicinal
Thomas J. Wubben, Sraboni Chaudhury, Brennan T. Watch, Jeanne A. Stuckey, Eric Weh, Roshini Fernando, Moloy Goswami, Mercy Pawar, Jason C. Rech, Cagri G. Besirli
Summary: This study developed a new generation of small-molecule PKM2 activators specifically designed for delivery into the eye to prevent photoreceptor death and vision loss.
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
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.
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.
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
Chemistry, Medicinal
Ping Wang, Hongqiong Yang, Weijiang Lin, Jingxian Zhou, Chengli Yu, Yinan Zhang, Yi Liu, Lingyu Ma, Mengting Li, Yang Hu, Qi Lv, Jian Liu, Lihong Hu
Summary: The D5 compound has been found to inhibit the differentiation of Th17 cells by suppressing PKM2-mediated glycolysis, restoring the Th17/Treg balance, and showing promising therapeutic effects against ulcerative colitis, making it a potential novel anti-UC candidate.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
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
Cell Biology
Fernanda O. Lemos, Ian de Ridder, Martin D. Bootman, Geert Bultynck, Jan B. Parys
Summary: PKM2 regulates calcium handling in the cytosol and mitochondria separately, while TAT-D5SD induces apoptosis by disrupting the PKM2:IP3R interaction.
Editorial Material
Hematology
Jane A. Little
Summary: Researchers cleverly improve red blood cell health in sickle cell disease patients by activating the enzyme PK in the glycolytic pathway, which reduces the concentration of 2,3-DPG and increases the oxygen affinity of HbS.
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
Multidisciplinary Sciences
Shan Lu, Yu Tian, Yun Luo, Xudong Xu, Wenxiu Ge, Guibo Sun, Xiaobo Sun
Summary: This study demonstrated for the first time that ISB targeted PKM2 to reduce macrophage inflammation, thereby significantly alleviating MI/R injury.
JOURNAL OF ADVANCED RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Xiaohui Lv, Honghong Zhou, Kai Hu, Ling Lin, Yongqiang Yang, Longjiang Li, Li Tang, Jiayi Huang, Yi Shen, Rong Jiang, Jingyuan Wan, Li Zhang
Summary: Accumulated evidence suggests that metabolic events play a significant role in the progression of various diseases, including liver injury. In this study, the metabolic status of pyruvate and its pharmacological significance in LPS/D-Gal-induced liver injury were investigated in mice. The findings indicate that the decline of pyruvate induced by LPS/D-Gal exposure may be a novel metabolic mechanism underlying the development of fulminant liver injury, and PKM2 activators or pyruvate derivatives may have potential value for pharmacological intervention.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Cardiac & Cardiovascular Systems
Prakash Doddapattar, Rishabh Dev, Madankumar Ghatge, Rakesh B. Patel, Manish Jain, Nirav Dhanesha, Steven R. Lentz, Anil K. Chauhan
Summary: This study demonstrates that myeloid cell-specific PKM2 regulates macrophage efferocytosis and atherosclerosis. Deletion or inhibition of PKM2 reduces atherosclerotic lesions, suppresses inflammation, and enhances macrophage efferocytosis.
CIRCULATION RESEARCH
(2022)
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
Microbiology
Osnat Tirosh, Yifat Cohen, Alina Shitrit, Odem Shani, Vu Thuy Khanh Le-Trilling, Mirko Trilling, Gilgi Friedlander, Marvin Tanenbaum, Noam Stern-Ginossar
Article
Biotechnology & Applied Microbiology
Shani Ben-Ari Fuchs, Iris Lieder, Gil Stelzer, Yaron Mazor, Ella Buzhor, Sergey Kaplan, Yoel Bogoch, Inbar Plaschkes, Alina Shitrit, Noa Rappaport, Asher Kohn, Ron Edgar, Liraz Shenhav, Marilyn Safran, Doron Lancet, Yaron Guan-Golan, David Warshawsky, Ronit Shtrichman
OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY
(2016)
Article
Biology
Adi Bercovich-Kinori, Julie Tai, Idit Anna Gelbart, Alina Shitrit, Shani Ben-Moshe, Yaron Drori, Shalev Itzkovitz, Michal Mandelboim, Noam Stern-Ginossar
Meeting Abstract
Oncology
Vered Behar, Osnat Bohana-Kashtan, Alina Shitrit, Daniel Sherman, Nili C. Schutz, Avihai Yakovan, Oren M. Becker
Meeting Abstract
Oncology
Vered Behar, Osnat Bohana-Kashtan, Alina Shitrit, Efrat Ben-Zeev, Alexander Konson, Rachel Ozeri, Tzofit Kehat, Sima Mirilashvili, Nili C. Schutz, Avihai Yacovan, Oren M. Becker
Review
Chemistry, Medicinal
I. Sela, G. Golan, M. Strajbl, D. Rivenzon-Segal, S. Bar-Haim, I. Bloch, B. Inbal, A. Shitrit, E. Ben-Zeev, M. Fichman, Y. Markus, Y. Marantz, H. Senderowitz, O. Kalid
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2010)
Article
Biochemistry & Molecular Biology
Ori Kalid, Martin Mense, Sharon Fischman, Alina Shitrit, Hermann Bihler, Efrat Ben-Zeev, Nili Schutz, Nicoletta Pedemonte, Philip J. Thomas, Robert J. Bridges, Diana R. Wetmore, Yael Marantz, Hanoch Senderowitz
JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
(2010)
Correction
Biochemistry & Molecular Biology
Gilad Wainreb, Haim Ashkenazy, Yana Bromberg, Alina Starovolsky-Shitrit, Turkan Haliloglu, Eytan Ruppin, Karen B. Avraham, Burkhard Rost, Nir Ben-Tal
NUCLEIC ACIDS RESEARCH
(2010)
Article
Multidisciplinary Sciences
Ron Edgar, Yaron Mazor, Ariel Rinon, Jacob Blumenthal, Yaron Golan, Ella Buzhor, Idit Livnat, Shani Ben-Ari, Iris Lieder, Alina Shitrit, Yaron Gilboa, Ahmi Ben-Yehudah, Osnat Edri, Netta Shraga, Yoel Bogoch, Lucy Leshansky, Shlomi Aharoni, Michael D. West, David Warshawsky, Ronit Shtrichman
Article
Genetics & Heredity
Ronna Hertzano, Ella Shalit, Agnieszka K. Rzadzinska, Amiel A. Dror, Lin Song, Uri Ron, Joshua T. Tan, Alina Starovolsky Shitrit, Helmut Fuchs, Tama Hasson, Nir Ben-Tal, H. Lee Sweeney, Martin Hrabe de Angelis, Karen P. Steel, Karen B. Avraham
Article
Multidisciplinary Sciences
Alina Shitrit, Daniel Zaidman, Ori Kalid, Itai Bloch, Dvir Doron, Tali Yarnizky, Idit Buch, Idan Segev, Efrat Ben-Zeev, Elad Segev, Oren Kobiler
SCIENTIFIC REPORTS
(2020)
Article
Biochemical Research Methods
G Getz, A Starovolsky, E Domany
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)