Article
Chemistry, Physical
Anika J. Friedman, Evan T. Liechty, Levi Kramer, Ankur Sarkar, Jerome M. Fox, Michael R. Shirts
Summary: Protein tyrosine phosphatases (PTPs) are potential drug targets for various diseases, but the design of selective therapeutics is complicated. This study investigates the allosteric inhibition of PTP1B by AD, an unusually selective inhibitor. Molecular dynamics simulations suggest that AD stably interacts with the allosterically influential region of PTP1B. The binding requires a disordered alpha 7 helix, contributing to the selectivity of AD. The findings indicate the potential of AD as a scaffold for building allosteric inhibitors of PTP1B.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Oncology
Alexander Drilon, Manish R. Sharma, Melissa L. Johnson, Timothy A. Yap, Shirish Gadgeel, Dale Nepert, Gang Feng, Micaela B. Reddy, Allison S. Harney, Mohamed Elsayed, Adam W. Cook, Christina E. Wong, Ronald J. Hinklin, Yutong Jiang, Eric N. Brown, Nickolas A. Neitzel, Ellen R. Laird, Wen - Wu, Anurag Singh, Ping Wei, Keith A. Ching, John J. Gaudino, Patrice A. Lee, Dylan P. Hartley, S. Michael Rothenberg
Summary: PF-07284892, an allosteric SHP2 inhibitor, combined with various oncogenic driver inhibitors, overcame bypass-signaling-mediated resistance in clinical settings. This combination therapy showed significant tumor and circulating tumor DNA responses, extending the duration of overall clinical benefit in patients with targeted therapy resistance in lung, colorectal, ovarian, and pancreatic cancer.
Article
Biochemical Research Methods
Nousheen Parvaiz, Asma Abro, Syed Sikander Azam
Summary: Protein Tyrosine Phosphatase 1B (PTP1B) is a negative regulator of insulin signaling pathways and has potential as a medicinal target. This study explores the binding and conformational orientation of zinc(II) complexes in PTP1B using advanced computational methods. The findings suggest that zinc(II) complexes can bind to important residues in the enzyme and inhibit its activity.
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
(2024)
Article
Plant Sciences
Zheng Zhang, Zhi-Peng Shang, Yan Jiang, Zhao-Xia Qu, Ren-Yong Yang, Jing Zhang, Ye-Xi Lin, Feng Zhao
Summary: Protein tyrosine phosphatase 1B (PTP1B) is an important target for treating type 2 diabetes. However, current PTP1B inhibitors lack selectivity and bioavailability. A study on Knoxia valerianoides led to the discovery of a unique anthraquinone-coumarin hybrid with good specificity for PTP1B. Further investigation of this plant led to the isolation of nine new anthraquinone glycosides and two known ones. All compounds showed PTP1B inhibitory activities, with compounds 4 and 8 exhibiting high selectivity for PTP1B over TCPTP.
JOURNAL OF NATURAL PRODUCTS
(2022)
Article
Biochemistry & Molecular Biology
James Adams, Benjamin P. Thornton, Lydia Tabernero
Summary: The study identified unique ligand cluster distributions specific to kinase interaction motif protein tyrosine phosphatases (KIM-PTPs) and found that ligand clusters coincide with functional and substrate binding sites in these PTPs. Ligand efficiency index (LEI) analysis showed that binders in these clusters reside in a more drug-like chemical-biological space. Differences in clusters across all KIM-PTPs highlight a distinct and specific profile for each phosphatase, with potential for exploiting unexplored allosteric functional sites for drug development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Mohd Saeed, Ambreen Shoaib, Munazzah Tasleem, Nadiyah M. Alabdallah, Md Jahoor Alam, Zeina El Asmar, Qazi Mohammad Sajid Jamal, Fevzi Bardakci, Saad S. Alqahtani, Irfan Ahmad Ansari, Riadh Badraoui
Summary: Diabetes mellitus is a major global public health issue, requiring the search for safe and effective drugs. Shikonin may serve as an anti-diabetic agent, showing competitive inhibitory effects on PTP1B, and has the potential to be a source for the production of preventive and therapeutic agents.
Article
Biochemistry & Molecular Biology
Joseph Farahany, Yoshikazu Tsukasaki, Amitabha Mukhopadhyay, Manish Mittal, Saroj Nepal, Chinnaswamy Tiruppathi, Asrar B. Malik
Summary: CD38 inhibits NLRP3 activation and can prevent endotoxemic ALI, suggesting it as a potential therapeutic target.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Tomasz Kostrzewa, Jakub Jonczyk, Joanna Drzezdzon, Dagmara Jacewicz, Magdalena Gorska-Ponikowska, Marcin Kolaczkowski, Alicja Kuban-Jankowska
Summary: One of the main goals of recent bioinorganic chemistry studies is to develop new substances for treating human diseases. This study focuses on the potential anticancer activity of vanadium-based compounds, specifically their inhibitory effect on PTP1B. The researchers synthesized five complexes and observed that they effectively inhibited PTP1B and exhibited anticancer activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Nguyen Viet Phong, Vu Thi Oanh, Seo Young Yang, Jae Sue Choi, Byung Sun Min, Jeong Ah Kim
Summary: This study isolated 30 phloroglucinols from Dryopteris crassirhizoma and identified trimeric phloroglucinols 26-28 as potent inhibitors of PTP1B, suggesting their potential for treating type 2 diabetes.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Review
Cell Biology
Francisca Cornejo, Bastian I. Cortes, Greg M. Findlay, Gonzalo I. Cancino
Summary: Protein phosphatases are key regulators of signal transduction, with the LAR-RPTP subfamily playing an important role in neurobiology, from neurodevelopment to brain disorders. The LAR-RPTP subfamily consists of three members in vertebrates and is involved in various brain functions.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Alberto J. Nunez-Selles, Lauro Nuevas-Paz, Gregorio Martinez-Sanchez
Summary: This study found that metal-mangiferin complexes have good antioxidant and protection against protein oxidative damage effects in the adjuvant therapies of neurodegenerative diseases, cancer, diabetes, and cardiovascular disorders. The coordination complexes of Se (IV) and Zn (II) with mangiferin showed significantly improved antioxidant/protective effects compared to isolated mangiferin.
APPLIED SCIENCES-BASEL
(2022)
Article
Chemistry, Multidisciplinary
Jinmin Miao, Jiajun Dong, Yiming Miao, Yunpeng Bai, Zihan Qu, Brenson A. Jassim, Bo Huang, Quyen Nguyen, Yuan Ma, Allison A. Murray, Jinyue Li, Philip S. Low, Zhong-Yin Zhang
Summary: In this study, researchers discovered the first highly potent and selective TC-PTP degrader called TP1L, which can induce degradation of TC-PTP and enhance T-cell signaling and tumor killing efficacy.
Article
Medicine, Research & Experimental
Takafumi Shintani, Ryoko Suzuki, Yasushi Takeuchi, Takuji Shirasawa, Masaharu Noda
Summary: This study aimed to explore the role of PTPRO in the control of glucose and lipid metabolism as well as obesity-induced systemic inflammation. Hyper-obese Ptpro-KO mice fed a high-fat/high-sucrose diet were used to investigate lipid accumulation, inflammatory cytokine expression, and insulin resistance. The effects of AKB9778, a specific inhibitor of PTPRO, on ob/ob mice and 3T3-L1 preadipocyte cells were also examined.
Article
Chemistry, Multidisciplinary
Nguyen Minh Trang, Le Ba Vinh, Nguyen Van Thanh, Nguyen Viet Phong
Summary: Novel therapeutic and preventative strategies are needed to slow down the progression of type 2 diabetes. In this study, modern spectroscopy techniques were used to determine the chemical structure of isosinensetin (ISO) isolated from trifoliate orange peel. ISO showed inhibitory activity against protein tyrosine phosphatase 1B (PTP1B) and exhibited potential as a drug-like candidate for treating type 2 diabetes.
Article
Biochemistry & Molecular Biology
Moran Shalev, Esther Arman, Merle Stein, Yael Cohen-Sharir, Vlad Brumfeld, Sergey Kapishnikov, Isabelle Royal, Jan Tuckermann, Ari Elson
Summary: The receptor-type protein tyrosine phosphatase PTPRJ is identified as an essential regulator specifically of osteoclast maturation. PTPRJ promotes osteoclast maturation by dephosphorylating the M-CSF receptor and Cbl, reducing the ubiquitination and degradation of NFATc1. Loss of PTPRJ inhibits osteoclast maturation by increasing ubiquitination of NFATc1 and reducing its amounts late in osteoclastogenesis.